Search PubMed⌕ Search

Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 433 records · Page 24Linked to original sources

Heterogeneity of the Graves' immunoglobulins directed toward the thyrotropin receptor-adenylate cyclase system.

The TSH-displacing and the thyroid-stimulating activities of Graves' immunoglobulins G (GIgG) have been accounted for by either homogeneous TSH receptor antibodies or heterogeneous antibodies directed toward the TSH receptor-adenylate cyclase system. To clarify this matter, the study of the interactions of GIgG preparations from 14 untreated Graves' patients with human thyroid membranes was undertaken. Dose-response curves of GIgG, diluted in IgG from normal subjects, were carried out in the [125I]TSH radioreceptor assay and the adenylate cyclase assay in the presence or absence of TSH. In the radioreceptor assay, GIgG were constantly negative in 3 cases (21%) and positive, depending of the dose, in 11 cases. In the adenylate cyclase assay, the dose-activity profiles in the absence of TSH were bell-shaped curves in 3 cases and sigmoid curves in 9 cases; in 2 cases (14%), GIgG preparations were devoid of any effect. Binding-isotherms and dose-activity profiles did not appear to share simple relationships. In the presence of TSH, GIgG preparations elicited a decrease in 6 cases, an increase in 3 cases, and no effect in 5 cases (36%) in the adenylate cyclase activity. The data obtained by radioreceptor assay and adenylate cyclase assay in the presence or absence of TSH were found statistically correlated (P less than 0.05 to P less than 0.001) but not linearly related, the points being scattered on specific parts of the diagrams. These observations could not be accounted for by TSH receptor antibodies in GIgG being an entity of constant properties, albeit varying in titer among patients. Rather, GIgG effects fit well the patterns of action of a heterogeneous ligand, as shown by computing a theoretical model for ligand heterogeneity with respect to binding equilibrium constant and intrinsic biological activity. Accordingly, GIgG activity in the TSH receptor-adenylate cyclase system could be attributed to heterogeneous antibodies varying with regard to binding constant and acting as stimulating or blocking antibodies of the adenylate cyclase.

Adenylyl Cyclases↗

Influence of antiganglioside antibodies on thyrotrophin binding and adenyl cyclase activity of thyroid plasma membranes.

Antibovine thyroid ganglioside antibodies developed in rabbits inhibit thyrotrophin binding to human thyroid plasma membranes. These antibodies are specific for gangliosides as was shown by the liposome agglutination technique. Antiganglioside antibodies did not stimulate basal adenyl cyclase activity in bovine thyroid plasma membranes, but most antiganglioside antibodies inhibit the activity of thyrotrophin stimulated adenyl cyclase. Antiganglioside antibodies react well with bovine thyroid plasma membranes and have considerable cross-reactivity with porcine and human thyroid plasma membranes. Rabbits which develop antiganglioside antibodies after some time have detectable levels of autoantithyroglobulin antibodies in their serum although the preparation used for imminisation did not contain any thyroglobulin or protein material.

Adenylyl Cyclases↗

Alteration of membrane fusion as a cause of acute pancreatitis in the rat.

Infusion of supramaximal doses of cerulein induces acute edematous pancreatitis in the rat. Cannulation of the main pancreatic duct does not prevent the formation of the edema but reveals an almost complete reduction of pancreatic flow. Using freeze-fracture techniques and thin-section electron microscopy, earliest structural alterations were observed at membranes of zymogen granules and the plasma membrane. Fusion of zymogen granules among each other leads to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fuse with the basolateral plasma membrane, discharging their content into the interstitial space. The findings indicate severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of a pancreatic secretagogue, which finally result in autodigestion of the pancreas.

Acute Disease↗

Inotropic, chronotropic and dromotropic effects of prenalterol, a new cardiostimulant drug.

Prenalterol (H 133/22) is an adrenergic beta-receptor stimulator which unlike isoproterenol is both orally active and has a long duration of action. The inotropic, chronotropic and dromotropic effects of prenalterol were investigated in pentobarbital anaesthetized dogs. Prenalterol was found to increase left ventricular maximum dP/dt in a dose-dependent manner up to a dose level of 50 micrograms/kg. Additional doses resulted in only small further increases in cardiac contractility. Electrophysiological studies were done to compare the effects of prenalterol and isoproterenol on sinus node and ventricular pacemaker function. Complete AV block was produced by electrocauterization of the His bundle. Prenalterol accelerated both ventricular and sinus node pacemakers at doses up to 50 micrograms/kg. The increase in ventricular rate was greater than the increase in sinus rate following supramaximal inotropic doses of prenalterol yet no ventricular extrasystoles were ever observed. Similar acceleration of the ventricular and sinus node pacemakers were observed by infusion of isoproterenol. Prenalterol and isoproterenol accelerated AV nodal conduction and ventricular conduction but had little effect upon His-Purkinje conduction. Sinus node reset time was abbreviated as was the functional and effective refractory periods of the atrium and AV nodes.

Animals↗

The borderline patient in the general hospital.

The usefulness of the general hospital inpatient service for the borderline patient is described. The short-term nature of most general hospital units requires a setting that facilitates the rapid establishment of a holding environment and the re-establishment of self-object transferences. Borderline patients have particular difficulty in accepting responsibility for their feelings and behavior and, instead, tend to blame themselves and others. An approach to inpatient care that defines expectations of both patient and family prior to and early in the admission of the patient is elaborated clinically and theoretically. Such an approach offers a way of working with the potential regression in borderline patients, especially around the important issues of responsibility and blaming. The staff's awareness of countertransference problems related to the patient and family as well as to the patient's therapist are described as important ingredients in successful work with these patients.

Attitude of Health Personnel↗

The borderline-narcissistic personality disorder continuum.

The author describes the usefulness of conceptualizing patients with borderline and narcissistic personality disorders along a continuum, using three main developmental lines. A clinical example demonstrates progression, during psychotherapy, from the borderline end of the continuum to the narcissistic personality disorder end.

Adaptation, Psychological↗

The mechanism of cytolysis of erythrocytes by the mushroom toxin phallolysin. Morphological and biochemical evidence for sodium influx and swelling.

Phallolysin, a basic protein of multiple molecular forms, was isolated from the mushroom Amanita phalloides. The toxic protein causes cytolysis in most mammalian cells at concentrations as low as 10(-8) M. Different from the cytolytic activities of detergents or sea-anemone toxin, cytolysis by low concentrations of phallolysin occurs only after a lag time of 2 to 3 minutes. In erythrocytes it was shown that phallolysin causes a rapid influx of sodium ions accompanied by a loss of potassium ions. Simultaneously, the cells swell up to their critical volume until they burst. In morphological studies the disruption of red blood cells following phallolysin treatment was found to be indistinguishable from that caused by incubation in hypotonic medium. Freeze-etching studies of phallolysin-treated erythrocytes showed changes in the membrane structure and a decrease of intramembranous particles. It is suggested that phallolysin either forms or opens preformed cation channels in the plasma membrane resulting in cation leakage. Concomitantly with the ion fluxes, water penetrates and causes the cells to swell until lysis occurs.

Amanitins↗

Substitution in vitro of lecithin-cholesterol acyltransferase. Analysis of changes in plasma lipoproteins.

Lecithin-cholesterol acyltransferase (EC 2.3.1.43) was purified 15 000-fold from human plasma. The active material was homogeneous in different gel electrophoretic systems but separated into three major bands with apparent pI values of 4.28, 4.33 and 4.37 in isoelectrofocusing. The apparent Mr of the enzyme is 67 000 +/- 2000. An antiserum prepared against the purified enzyme specifically inhibited the activity of lecithin-cholesterol acyltransferase in whole serum. Serum from a patient with familial deficiency of lecithin-cholesterol acyltransferase was substituted in vitro with the highly purified enzyme. The serum from this patient did not contain immunochemically detectable enzyme protein. Substitution of enzyme resulted in the following major changes. 1. Cholesteryl ester content in serum increased by 36-89 mg/100 ml depending on the experimental conditions. The enzyme-mediated formation of cholesteryl ester led to an increase of cholesteryl ester content in high-density and very-low-density lipoproteins and in low-density lipoproteins containing apoprotein-B. No increase occurred in fractions containing very large flattened structures and the abnormal lipoprotein-X and in lipoprotein-E. Incubation of isolated fractions with lecithin-cholesterol acyltransferase led to significant cholesterol esterification only in high-density lipoproteins. 2. The characteristic disc-shaped rouleaux-forming high-density lipoproteins of enzyme-deficient serum disappeared. Instead a single homogeneous population of high-density lipoproteins formed. The particles generated were spherical and had the electrophoretic properties, density (1.080 g/ml), diameter (12.5 nm) and apoprotein composition of normal high-density lipoproteins-2. 3. The concentration of spherical particles containing apolipoprotein E (density 1.040-1.080 g/ml) and the lamellar lipoprotein-X-like structures in the low-density lipoprotein fraction were not affected by the enzyme substitution. 4. A single homogeneous population of spherical lipoprotein-B particles of 26.5-nm diameter occurred at density 1.029 g/ml. The data suggest that the discoidal high-density lipoproteins are the major site of cholesteryl ester formation that apolipoprotein-E is not involved in an undirectional transport of newly formed cholesteryl ester from high-density lipoproteins to other lipoproteins and that lipoprotein-X and lipoprotein-E are not preferential substrates for the acyltransferase.

Apolipoproteins↗

Effect of somatostatin on rat exocrine pancreatic secretory process in normal and diseased state.

The effect of somatostatin on the secretory process of the rat exocrine pancreas has been studied using a combined in vivo- in vitro system. Somatostatin in a concentration of 5 x 10(-6) g/kg/h was infused alone or in combination with low (5 x 10(-7) g/kg/h) and high (5 x 10(-6) g/kg/h) doses of synthetic caerulein. All aspects of the secretory process were then studied in vitro using isolated pancreatic lobules. Somatostatin inhibits both basal and stimulated discharge of enzymes and newly synthesized proteins thus leading to increased enzyme content. The stimulatory action of low doses of caerulein is nearly totally blocked, however, the induction of an acute non-hemorrhagic interstitial pancreatitis due to supramaximal doses of caerulein is not prevented, but only reduced in its severity. Furthermore, somatostatin infusion following the induction of pancreatitis has a beneficial effect on recovery, since increase levels of pancreatic enzymes in blood are quickly reduced and cellular infiltration of the diseased pancreas is nearly prevented.

Animals↗

[Pyroderma fistulans sinifica associated with congenital alpha-1-antitrypsin deficiency].

A patient is reported who suffered from pyodermia fistulans sinifica (acne conglobata sinifica, acne tetrade) and who presented a severe congenital alpha-1-antitrypsin deficiency (phenotype ZZ). The possible significance of the protease inhibitor deficiency for the development of this disease is discussed. Alpha-1-antitrypsin deficiency has been observed in several dermatoses (panniculitis, cutaneous vasculitis, Ehlers-Danlos syndrome, acquired angioneurotic edema and cold urticaria). The insufficient neutralization of liberated leukocyte proteases has been considered to play an important role in these disorders. Besides the ultrastructural finding in the liver cell which is typical for alpha-1-antitrypsin deficiency crystals were found as are seen in the cholesterol ester storage disease. This was probably caused by an increased influx of fatty acids.

Female↗

Transference, real relationship and alliance.

The study of primitive patients, i.e. patients with borderline and narcissistic personality disorders, is utilized to examine the concepts of transference, the real relationship and therapeutic alliance in the treatment of all patients. Self-object transferences are present in the psychoanalytic treatment of primitive as well as neurotic patients. In neurotic patients they form the silent stable framework upon which the neurotic dyadic and triadic transferences emerge. The complex meanings of the patient's real relationship with the analyst are explored. In primitive patients the real or objective qualities of the analyst are perceived after self-object transferences are established. These objective attributes are then available for internalization if they are deficient and needed by the patient. The mature therapeutic alliance derives from the resolution of self-object and neurotic transferences; it requires the patient's capacity to separate the personal or real relationship with the analyst from the transference. Although precursors are visible and utilized earlier, a mature therapeutic alliance is usually not present until the later phases in the analytic treatment of neurotic patients. The therapeutic alliance concept is examined from the vantage point of its tenuous existence in primitive patients, and its slow development in neurotics. Its confusion with self-object transferences is discussed and related in part to the analyst's need to utilize the therapeutic alliance concept to help him with his loneliness and aloneness in his analytic work.

Borderline Personality Disorder↗