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Biomedical subjects

G Sager

Publications and source records attributed to G Sager.

At least 91 records · Page 5Linked to original sources

Binding of catecholamines to alpha-1 acid glycoprotein, albumin and lipoproteins in human serum.

The binding of catecholamines in human serum was determined by equilibrium dialysis at 37 degrees. For serum concentrations of 10-15 nM the bound fractions were 28.8 +/- 2.2%, 25.7 +/- 1.7% and 22.2 +/- 2.2% for (+/-)-isoproterenol (IPR), (+/-)-norepinephrine (NE) and (+/-)-epinephrine (EPI), respectively. At higher serum concentrations saturation occurred. Alpha-1 acid glycoprotein (AAG) possessed one high affinity binding site and approximately 10 low affinity sites. The catecholamines were bound to AAG with the same order of potency for both classes of binding sites: IPR (Kd1: 100 microM Kd2: 2.2 mM) greater than NE (Kd1: 120 microM, Kd2: 6.5 mM) greater than EPI (Kd1: 140 microM, Kd2: 14 mM). Human serum albumin (HSA) and lipoproteins (SLP) interacted with the catecholamines in a non-saturable manner. IPR showed the strongest and EPI the weakest association to both of these serum protein fractions. (-)-Propranolol was able to inhibit the binding of IPR in serum and to isolated AAG, but not to HSA or to SLP. The present results show that AAG is an important catecholamine-binding protein in human serum. AAG, but not HSA or SLP, possesses binding sites shared by adrenergic receptor stimulators and blockers.

Binding Sites↗

Distribution of nortriptyline in human blood: effects of temperature, pH, and drug concentration.

An in vitro study of putative factors causing postvenipuncture redistribution of the tricyclic antidepressant nortriptyline (NT) in blood was carried out in blood samples from a single subject. The influence of varying temperature, pH, and drug concentration on the protein binding of NT was assessed by equilibrium dialysis. The influence of the same variables on the distribution of NT in whole blood was measured by calculating the cell/plasma (C/P) drug concentration ratios after centrifugation of blood samples. Variation in temperature did influence the distribution of NT in blood considerably. From 4 to 37 degrees C, the C/P ratio was found to increase from 1.0 +/- 0.1 to 1.7 +/- 0.2, and protein binding expressed as unbound fraction from 2.9 +/- 0.2 to 7.0 +/- 1.1% (mean +/- SD). Neither pH variations within the 7.0-7.6 range, nor variations in drug concentration, were found to alter NT distribution at 37 degrees C. The observed effect of temperature on NT distribution shows that handling of blood samples from patients taking NT should be standardized in order to avoid errors of interpretation.

Buffers↗

Orthopaedic considerations in obstetric brachial plexus palsy.

Obstetric brachial plexus palsies are seen in orthopaedic practice today despite improved obstetric care. The incidence is believed to be 0.35 to 0.87 cases per 1,000 live births. The pathomechanics of these injuries are not fully understood, although numerous risk factors have been identified. Large birth weight, breech presentation, shoulder dystocia, and forceps-assisted deliveries have all been implicated. No one standard treatment modality exists. Therefore, the treating orthopaedist must be familiar with this entity and with the various accepted treatment approaches in order to formulate the appropriate therapy for a particular patient.

Brachial Plexus↗

[Kunze-Murken growth-specific approximations of somatograms].

Tables for human height at age values by Kunze and Murken are submitted to mathematical approximations applying the 2-step-model introduced by Sager (1981). The basic term reflects growth as expected when a growth spurt is lacking which may be the case for children with chromosomal aberrations. The 2nd term comprises an expression for the growth spurt proper thus allowing an evaluation for the intensity of the spurt. The approximations as gained with nonlinear regressions show very close agreement with the measurements. Besides the growth curve its first derivative--the growth velocity or increase--is calculated and represented graphically. Moreover the results and their relative amounts against the final values at adulthood are compared for nine height at age tables treated hitherto with the same growth model.

Adolescent↗

[Thoughts on a mathematical understanding of the growth of experimental tumors].

A contribution by Krug and Taubert concerning the mathematical approximation of Ehrlich ascites tumor growth using logit transformation of the logistic function followed by an approximation of the prefinal decline of the cell number gives rise to further contemplations. The authors aimed at a rather simple method to be realised with programmable pocket computers. A proposal offered by Dr. Krug lead the author to further investigations into the problem in question. As one possibility the sigmoidal function is replaced by a special form of the Janoschek function whilst the multiplicative descending exponential function mainly responsible for the prefinal stage is given a more flexible character. As a result the ascending phase is only slightly altered whereas the stage of decline shows different behaviour partly due to the few and scattering input data for this branch of the growth curve. By this method linear deviations are reduced by about a quarter in the example treated.

Animals↗

[Relation between body height and weight in adult humans].

Series of values for body height of adults ranging from 150 to 190 cm and the corresponding body weights for 9 age groups from 15 to 65 a are interrelated by 5 test functions. Results of nonlinear regressions as gained by minimization of the sums of the squares and absolute values of the deviations are summarized in tables for comparison. The last position in the goodness-of-fit is held by the allometric relation W = alpha L beta preceded by the exponential type W = abL. No considerable gain can be realised by taking the expression W = a exp (b Lp). A big step is reached, however, with the change to the form W = W150 + alpha (L-150) beta reducing the linear deviations to about 1/3 or more. Finally the 3-parameter structure W = W A + alpha (L-150) beta yields even closer approximations. Tables with the results for the last 2 relations are given together with a graph for the best approximation.

Adolescent↗

Elevated level of beta-adrenergic receptors in hepatocytes from regenerating rat liver. Time study of [125I]iodocyanopindolol binding following partial hepatectomy and its relationship to catecholamine-sensitive adenylate cyclase.

Hepatocytes from regenerating rat liver show an enhanced epinephrine-sensitive adenylate cyclase activity and cAMP response, which may be involved in triggering of the cell proliferation. We have determined adrenergic receptors and adenylate cyclase activity in hepatocytes isolated at various time points after partial hepatectomy. The number of beta-adrenergic receptors, measured by binding of [125I]iodocyanopindolol ([125I]CYP) to a particulate fraction prepared from isolated hepatocytes, increased rapidly after partial hepatectomy as compared with sham-operated or untreated controls. The maximal increase, which was observed at 48 h, was between 5- and 6-fold (from approximately 1 800 to approximately 10 500 sites per cell). Thereafter, the number of beta-adrenergic receptors decreased gradually. Competition experiments indicated beta 2-type receptors. Parallelism was found between the change in the number of beta 2-adrenergic receptors and the isoproterenol-responsive adenylate cyclase activity. The number of alpha 1-adrenergic receptors, determined by binding of [3H]prazosin, was transiently lowered by about 35% at 18-24 h, with no significant change in Kd. Although the results of this study do not exclude the possibility of post-receptor events, they suggest that the increased number of beta 2-adrenergic receptors is a major factor responsible for the enhanced catecholamine-responsive adenylate cyclase activity in regenerating liver.

Adenylyl Cyclases↗

Effect of serum, alpha-1 acid glycoprotein, lipoproteins and albumin on human mononuclear leucocyte beta-adrenoceptors.

The effects of serum, alpha-1 acid glycoprotein (AAG), serum lipoproteins (SLP) and human serum albumin (HSA) on 3H-(-)-dihydroalprenolol (3H-(-)-DHA) binding and (-)-isoproterenol ((-)-IPR) induced cyclic AMP (cAMP) elevation in human peripheral blood mononuclear leucocytes (MNL) were investigated. The saturable binding of 3H-(-)-DHA was decomposed into two classes of binding sites with maximum binding capacity of approximately 1400 and 30000 sites/cell and with dissociation constants (Kd) of approximately 0.7 and 65 nM. Stimulation of the MNL beta-adrenoceptors by (-)-IPR caused a concentration dependent cAMP accumulation (EC50 approximately 0.2 microM) with maximum level approximately 250% above basal. For all single leucocyte preparations, 30-35 min. exposure to serum, AAG and SLP increased the number of beta-adrenoceptors with 100-200% and the maximal responsiveness to (-)-IPR with 30-90%. The presence of proteins did not change the Kd or the EC50. (-)-Alprenolol inhibited concentration dependently the serum induced increment in (-)-IPR-responsiveness. Serum, AAG and SLP did also increase the number of low affinity binding sites with 25-40% without effect on the Kd. HSA had no consistent effect on beta-adrenergic binding or stimulation. The present study shows that serum, AAG and SLP influence the number and function of MNL beta-adrenoceptors in vitro.

Alprenolol↗

[Growth models and growth spurt in the human].

Growth of man differs basically from that of all animals - perhaps except some species of primates - by demonstrating a puberal growth spurt. This behaviour is well known but was hardly ever analyzed in a mathematical manner. The growth spurt is indeed difficult to grasp and this all the more as it shows varying forms of appearance. This becomes evident by the investigation of height values for normal and growth-restricted children as is the case with genetic diseases. From these variants, PELZ and SAGER came to the conclusion of setting up differentiated forms of growth spurts with adequate definitions in mathematical formulation. In this contribution, the models of human height growth and height velocity as practiced at Zurich (working group PRADER), London (working group TANNER) and Rostock (PELZ, SAGER, EYERMANN) are recalled and scrutinized as to the applicability of the new definitions. After the somewhat difficult comparisons of the model structures meditations are focussed at the proposals for the definition of the duration and the intensity of the growth spurt leading to quite different conceptions. Relative agreement is present for the time of the onset of the spurt whilst larger differences appear for the end of the puberal phase. A complete coincidence can hardly be reached but at least some light is thrown on this intricate problem by analyzing the different points of view.

Adolescent↗

[Growth specific analysis of Schmid's (1983) data on Down syndrome carriers].

After a short introduction to the phenomena of children with Down's syndrome, values describing body status as gained by Schmid at the Aschaffenburg hospital for child disease (F.R.G.) are recalled. In a cross-sectional study values for body height, head circumference and body weight for 393 girls and 436 boys were gathered in 1983 reflecting the status for medically treated patients of the present. After insuring that the scattering of the data keeps within tolerable limits growth specific analysis became a challenge. Body length is approximated with the 2 step model by Sager (1981) comprising a basic function without a growth spurt superimposed by a spurt term. As a result, an usual but somewhat reduced growth spurt can be secured for the girls whilst the boys show no intermediate maximum in growth velocity. Nevertheless velocity keeps well above that for the basic function thus indicating a silent spurt after the definition of Pelez and Sager (1984). Head circumference too is treated with the same model after tests with Czech values for common and gypsy children. As a result, a reduced but acute growth spurt with a growth hump for the increase function has been found for both sexes. In contrast to height, however, a short term formula for values from birth to near pubescence cannot be applied due to the vivid head growth in the postnatal phase. Values for body weight W allow first conclusions after plotting log W against the body length L. In the case of the Down patients, 2 different forms of fundamental relations emerge, one of them related to normal growth, the other to impeded or less differentiated development as found in the rhesus for example. For both cases, mathematical expressions as proposed and used by Sager are applied. Results show near to normal behaviour for the girls and a less intricate course in weight growth for the boys. Results are given in graphs and tables allowing detailed calculations if desired. Quotients of momentary to finally attained values for body height and weight as well as head circumference are added.

Adolescent↗

Increased number of beta-adrenoceptors in hepatocytes from rats treated with 2-acetylaminofluorene.

Treatment of rats with chemical carcinogens, including 2-acetylaminofluorene (2-AAF), leads to a strong increase in the hepatic catecholamine-sensitive adenylate cyclase activity. The present study was undertaken to investigate the mechanism for the development of this increase. We report that hepatocytes isolated from rats which had been fed 2-AAF (0.025% w/w) for 8-12 weeks had an increased number of beta-adrenoceptors, as determined by [3H]dihydroalprenolol binding to whole cells and [125I]iodocyanopindolol binding to washed particles. For both ligands the number of binding sites was about 4-fold higher in hepatocytes from 2-AAF-treated rats than in those from controls. The adenylate cyclase activity of the carcinogen-fed animals showed both a general increase manifested in the basal level (2-fold) and in the activities obtained by stimulation with guanine nucleotides (2-3-fold), cholera toxin (1.5-fold), and glucagon (1.3-fold) and a selective, larger increase in the beta-adrenoceptor-linked activity (7-fold increment of the isoproterenol-sensitive activity). The results indicate that the number of hepatocyte beta-adrenoceptors increases during 2-AAF carcinogenesis. This may, at least in part, explain the rise in catecholamine-sensitive adenylate cyclase activity.

2-Acetylaminofluorene↗

[Growth in length of the bearded seal (Erignathus barbatus, Erxleben 1777) following Benjaminsen (1973) data].

Length data for almost 200 bearded seals around Svalbard and in the Barents Sea gained in 1968 and 1970 by Benjaminsen are taken as a basis for mathematical considerations. Age has been deduced from annual bandings of teeth in the upper jaw and in the claws. In the original treatment a curve for length growth has been drawn by eye despite severe scattering of the basic data. The mathematical methods now available allow approximations by growth functions and lead to a surprising agreement for 5 functions of quite different structure. Tables and graphs are added for the development of length growth and increase respectively.

Age Factors↗

Effect of serum on isoproterenol-induced cyclic AMP accumulation in human lymphocytes.

The effects of autologous serum on basal and isoproterenol (IPR) or prostaglandin E1 (PGE1) stimulated adenosine 3',5' cyclic monophosphate (cAMP) levels were investigated in human lymphocytes. For all blood donors, serum (25% (v/v)) lowered the basal cAMP content. In contrast, the responsiveness of the lymphocyte cAMP accumulation to (-)-IPR was increased. This effect was most clearly demonstrable in bicarbonate buffered incubation medium (40-50% increase of maximal response), but was also seen in phosphate buffered medium (10-20% increase). Serum did not alter the sensitivity of the lymphocytes to IPR. The response to PGE1, which was a considerable more effective stimulator of cAMP accumulation than IPR, was not affected in any consistent way by serum. The results indicate that serum influences the regulation of lymphocyte cAMP and that this effect may partly be exerted at the level of the beta-adrenoceptors.

Alprostadil↗

[Approximations for growth in weight and length of the golden hamster (Mesocricetus auratus Waterhouse) following data of Du Bois (1950)].

Weight and length of body as well as length of tail and right hind leg of 111 golden hamsters after Du Bois (1950) are submitted to approximations with several functions of organic growth. As already verified for rats and mice the generic growth function has priority in representing weight whilst length series of the golden hamster are expressed best by a formulation of Sager (1980a). Allometric relations are rather poor between weight and length and fail altogether between total and partial lengths. Special remarks are added concerning calculations of allometric parameters.

Animals↗