Eye-muscle membrane antibodies in autoimmune orbitopathy.
Explore the source record for details and available documents.
Autoantibodies↗
Biomedical subjects
G Adler
Publications and source records attributed to G Adler.
[The hyperarousal hypothesis: new aspects of a neurophysiologic concept of endogenous psychoses].
The hyperarousal hypothesis has been developed as a concept of the major psychoses on the basis of neurophysiological findings on the function of the reticular formation. An enduring hyperactivity of the ascending reticular activation system is assumed to be characteristical for the major psychoses. Recently, studies on the habituation of auditory evoked potential components provided new evidence supporting the hyperarousal hypothesis. Thus, by means of the auditory evoked potential investigation an electrophysiological assessment of the hyperarousal state in patients with major psychoses has become feasible. These findings may have important implications for the research on the major psychoses and may find clinical applications.
Arousal↗
Role of cholecystokinin in cholestyramine-induced changes of the exocrine pancreas.
This study was an investigation of the role of cholecystokinin (CCK) in the stimulatory action of cholestyramine on rat exocrine pancreas. Postprandial CCK release was significantly enhanced by acute administration of cholestyramine (12.7 +/- 1.8 vs 3.7 +/- 0.5 pmol/L in controls). Over four weeks, rats were fed either regular diet or diet containing 6% cholestyramine, and were treated with the specific CCK receptor antagonist L-364,718 (2 x 0.5 mg/kg body weight/day s.c.) or DMSO (vehicle for the antagonist). Cholestyramine significantly increased pancreatic weight and trypsin and chymotrypsin contents. L-364,718 abolished these effects. Concomitant administration of antagonist and cholestyramine elevated amylase content, compared to controls. CCK levels in fasted animals did not differ between the four groups. The effect of the same dose of L-364,718 on pancreatic enzyme depletion, induced by the protease inhibitor camostate, was studied in a control experiment. A single dose of camostate (200 mg/kg) caused a 44-68% decrease in enzyme content. L-364,718 reversed this effect for all enzymes. We conclude that CCK is the mediator of cholestyramine-induced pancreatic hypertrophy and increase in content of proteases. After long-term administration, the CCK receptor antagonist, in combination with cholestyramine revealed an agonistic effect on individual, pancreatic enzyme content.
Administration, Oral↗
CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat.
The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of 125I-CCK-8 in pancreatic acini dose dependently by 39-93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas.
Animals↗
Evidence of intracellular activation of serine proteases in acute cerulein-induced pancreatitis in rats.
It is believed that activation of zymogen proteases occurs in the early development of acute pancreatitis. This hypothesis was proved on subcellular fractions of rat pancreas after induction of pancreatitis by infusion of high doses of cerulein for 2 h. Secretory enzyme activities were measured spectrophotometrically in subcellular fractions obtained by differential ultracentrifugation. Additionally, trypsin and chymotrypsin activities were detected by enzyme blots after isoelectric focusing. Finally immunoblotting (Western-blot analysis) for amylase, lipase, trypsin/ogen, and chymotrypsin/ogen was carried out on fractions separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). In cerulein pancreatitis, subcellular fractions of secretory granules and vacuoles showed significant amounts of free trypsin and chymotrypsin activities compared with controls. The presence of free activities of serine proteases was paralleled by the appearance of numerous low molecular weight peptides detected by 2-dimensional electrophoresis and SDS-PAGE, which in part represented proteolytically cleaved secretory proteins. It is concluded that the intracellular activation of serine proteases that occurs in cerulein pancreatitis could contribute to further acinar cell destruction.
Amylases↗
Mechanism of acute pancreatitis. Cellular and subcellular events.
A membrane-bound system through which secretory and lysosomal proteins travel in a vectorial fashion is essential for the preserved integrity of pancreatic acinar cells. This system is composed of an ordered array of compartments, such as the rough endoplasmic reticulum, the Golgi complex, lysosomes, and secretory granules. As a principle, in acute pancreatitis the final steps of this transport seem to be disturbed. Caerulein-induced pancreatitis is a valuable experimental model for studying altered intracellular transport, and compartmentation of lysosomal and digestive enzymes. The formation of enlarged secretory vacuoles containing lysosomal and digestive enzymes is paralleled by the activation of lysosomes and degradation of cellular organelles in autophagosomes. On the level of secretory and autophagic vacuoles, activation of serine proteases occurs, which in addition to increasing lysosomal enzyme activities can represent the initial stage for acinar cell destruction and the development of pancreatitis.
Acute Disease↗
[Effect of pellet size of a pancreas enzyme preparation on duodenal lipolytic activity].
Release of lipolytic activity from enteric coated microspheres occurs after emptying from the stomach. Gastric emptying of the spheres is strongly influenced by their size, as several studies indicate. In the present study 10 patients with exocrine pancreatic insufficiency received two types of enzyme substitution (Kreon) and were investigated using the cholesterol-14C-octanoate breath test. Preparation A with microspheres of the size 1.0-1.2 mm and B with the size 1.8-2.0 mm. All patients showed an obvious delay in intraduodenal lipolytic activity using the 1.8-2.0 mm preparation. In 3 out of 10 patients lipolytic activity increased much more early using the 1.0-1.2 mm preparation, in the other patients differences were not as clear. The effectiveness of enzyme substitution was 25% greater for the 1.0-1.2 mm preparation for the time of testing (mean values, p less than 0.10).
Adult↗
[Neuro-monitoring using visual evoked potentials in comatose neurologic intensive care patients].
The application of visual evoked potentials (VEP) as a monitoring tool was studied in 40 comatose neurological intensive care patients. With increasing depth of coma, the number of detectable VEP components decreased. In deeply comatose patients, VEP were regularly displayed as a negative wave with a latency of app. 100 ms and an amplitude of app. 8 microV (N100). The administration of promethazine or flunitrazepam used as sedatives produced a decrease of amplitude and an increase of latency of N100 that was reversed within 30 or 60 min respectively. In 10 patients, in which intraventricular pressure (IVP) was measured continuously by means of an intraventricular catheter, it was found that increases of IVP produced a considerable decrease of the amplitude and area of N100; after reduction of the increased IVP, both parameters quickly recovered. These observations indicate that VEP may be a useful tool for neuro-monitoring in neurological intensive care patients.
Adult↗
[Functional syndromes of the gastrointestinal tract].
Explore the source record for details and available documents.
Arousal↗
[Mechanisms of postprandial stimulation of gastrointestinal motility and pancreatic secretion].
Explore the source record for details and available documents.
Animals↗
Cholecystokinin is a regulator of intestinal phase-stimulated PP release.
The purpose of this study was to determine the role of CCK during the intestinal phase of pancreatic polypeptide (PP) release in man. We first compared the PP response to exogenous caerulein infusion in the presence or absence of either loxiglumide (a specific CCK antagonist) or atropine in six healthy subjects. In the second part of the study, a meal was perfused to the duodenum with and without either loxiglumide or atropine. Both loxiglumide and atropine completely abolished the PP response to exogenous or endogenous stimulation (P less than 0.05). We conclude that CCK participates in the intestinal phase of PP secretion.
Adult↗
Structural alterations of pancreatic microvasculature in cerulein-induced pancreatitis in the rat.
Pancreatic microvasculature in cerulein-induced pancreatitis was studied at the electron and light microscopic level. Using a modified model of in situ india ink perfusion, focally a marked reduction of the number of india-ink-filled microvessels was found. The numerical density (NA) of filled microvessels was reduced by 66.7% in pancreatitis. The morphological correlate for this extreme numeric reduction might be a collapse of the lumen of pancreatic microvessels. In the presence of cerulein pancreatitis 42% of pancreatic capillaries had a collapsed lumen as shown by electron microscopy. The endothelium of capillaries in acute pancreatitis demonstrated surface blebbing, the formation of cytoplasmatic vacuoles, edema, and swollen mitochondria. Some capillaries had irregularities at the interendothelial junction, and the majority of examined vessels were surrounded by marked perivascular edema. No strict correspondence between histological signs of pancreatitis and light microscopic and/or ultrastructural microvascular alterations could be demonstrated. Our study emphasizes that alterations of microvasculature are present early in experimental edematous pancreatitis. Therefore, alterations of pancreatic microcirculation seem to be of great importance in the pathogenesis of pancreatic inflammation, and should be the subject of further studies.
Animals↗
Cerulein-induced acute pancreatitis in rats: evidence for reduced calcium affinity of secretory granule membranes.
Membranes of secretory granules in pancreatic acinar cells seem to be interrelated in the regulation of intragranule Ca2+ concentrations. Since low intragranule Ca2+ levels are involved in zymogen stabilization versus autoactivation of proteases, a disturbance of the Ca2(+)-regulating system in secretory granules could be invoked to account for uncontrolled proenzyme activation. This is proposed as the initial mechanism in the pathogenesis of acute pancreatitis. Using pancreatic subcellular fractions obtained from control rats and after induction of acute cerulein pancreatitis we found a markedly reduced Ca2+ affinity of membranes from the secretory granule fraction in pancreatitis. The strong Ca2+ binding of control zymogen granule membranes primarily seemed to be a function of non-proteinacous membrane components, e.g. phosphatidylinositols. It is suggested, that part of the inner surface of membranes from secretory granules acts as a calcium-buffering system that works in synergy with other protective mechanisms to stabilize the zymogen granule population. In cerulein pancreatitis there seemed to be an imbalance of this system.
Animals↗
Glycoconjugate pattern of membranes in the acinar cell of the rat pancreas.
Lectin-binding studies were performed at the ultrastructural level to characterize glycoconjugate patterns on membrane systems in pancreatic acinar cells of the rat. Five lectins reacting with different sugar moieties were applied to ultrathin frozen sections: concanavalin A (ConA): glucose, mannose; wheat-germ agglutinin (WGA): N-acetylglucosamine, sialic acid; Ricinus communis agglutinin I (RCA I): galactose; Ulex europaeus agglutinin I (UEA I): L-fucose; soybean agglutinin (SBA): N-acetylgalactosamine). Binding sites of lectins were visualized either by direct conjugation to colloidal gold or by the use of a three-step procedure involving additional immune reactions. The rough endoplasmic reticulum and the nuclear envelope of acinar cells was selectively labelled for ConA. The membranes of the Golgi apparatus bound all lectins applied with an increasing intensity proceeding from the cis- to the trans-Golgi area for SBA, UEA I and WGA. In contrast RCA I selectively labelled the trans-Golgi cisternae. The membranes of condensing vacuoles and zymogen granules were labelled for all lectins used although the density of the label differed between the lectins. In contrast the content of zymogen granules failed to bind SBA and WGA. Lysosomal bodies (membranes and content) revealed binding sites for all lectins used. The plasma membranes were heavily labelled by all lectins except for SBA which showed only a weak binding to the lateral and the apical plasma membrane. These results are in accordance to current biochemical knowledge of the successive steps in the glycosylation of membrane proteins. It could be demonstrated, that the cryo-section technique is suitable for the fine structural localisation of surface glycoconjugates of plasma membranes and internal membranes in pancreatic acinar cells using plant lectins.
Animals↗
Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor. III. Changes in DNA synthesis and mitotic activity.
Previous studies with rats have shown that a single oral dose of the proteinase inhibitor Camostate (FOY-305) induces release of cholecystokinin (CCK) into the circulation, which lasts for 3 to 6 h. This transient endogenous release of hormone results in a depletion of pancreatic enzyme stores within 1 h and an increase in total rate of protein synthesis, which peaks at 6 to 9 h. At the level of individual enzyme biosynthesis a transient decrease in amylase and an increase in trypsinogen and chymotrypsinogen is observed. In the present study the time course of DNA synthesis and the labeling index of 5 populations of pancreatic cells have been analysed following a single oral dose of 50 or 100 mg/kg proteinase inhibitor, using in vivo labeling with 12 microCi/g body weight 3H-thymidine 1 h prior to sacrifice of the animals. DNA synthesis did not change during the initial 12 h following inhibitor feeding and then showed a phasic increase with a peak (20-fold) at 24 h and intermediate increases (4- to 5-fold) at 18 and 36 h, respectively. From the 5 pancreatic cell populations studied by autoradiography the labeling indices of interlobular duct cells and islet cells did not change over the entire observation period. Acinar cells, intralobular duct cells and interstitial cells showed a marked increase in labeling index with peak values at 24 h, which were 20-fold in acinar cells and 5.5- and 8.5-fold in intralobular duct cells and interstitial cells, respectively. The data demonstrate a significant growth response of pancreatic acinar tissue after a single episode of endogenous CCK-release, which is similar in extent, time course and cellular source as previously demonstrated during persistent stimulation of the pancreas by prolonged infusion of the CCK-analogue caerulein.
Animals↗
Caerulein-induced acute pancreatitis in rats: changes in glycoprotein-composition of subcellular membrane systems in acinar cells.
Caerulein-induced acute pancreatitis is characterized by the occurrence of two membrane-bound vacuolar systems in acinar cells. Beside digestive enzymes containing secretory vacuoles, lysosomal autophagic structures can be identified at the ultrastructural level. In the present study glycoconjugate patterns of the surrounding membranes were characterized by ultrastructural lectin-binding experiments using five colloidal-gold labeled lectins with distinct sugar specificities. Furthermore, the profile of membrane glycoproteins of isolated vacuolar fractions was studied by SDS-PAGE and lectin-blotting. In pancreatitis, membranes of secretory vacuoles showed a significant lower degree of lectin-binding compared to normal zymogen granules. In contrast, newly appearing autophagic vacuoles in pancreatitis revealed a strong membrane labelling for most lectins used. The pattern of membrane glycoproteins of secretory and autophagic vacuoles as determined by SDS-PAGE and lectin-blotting differed from those of normal zymogen granules resembling the protein profile of smooth microsomes. Since this pattern requires a previous passage through Golgi stacks, it is assumed that the two types of vacuoles derive from Golgi elements. For the pathogenesis of caerulein pancreatitis these vacuolar post-Golgi structures seem to play an important role.
Acute Disease↗
Localization of lysosomal and digestive enzymes in cytoplasmic vacuoles in caerulein-pancreatitis.
Intracellular localization and enzymatic activities of lysosomal enzymes (cathepsin B, N-acetyl-beta-glucosaminidase, and beta-glucuronidase) were studied in control rats and after induction of caerulein pancreatitis. In control rats high enzymatic activities were found in the postnuclear 1000 g fraction (purified zymogen granules). The corresponding subcellular fraction in pancreatitis animals additionally contained larger secretory vacuoles and autophagosomes and revealed a marked increase in lysosomal enzyme activities. Immunolabelling studies at the ultrastructural level for trypsinogen and cathepsin B demonstrated a colocalization of lysosomal and digestive enzymes in zymogen granules in healthy controls. After induction of pancreatitis immunolabelling still demonstrated a colocalisation of cathepsin B and trypsinogen in secretory granules and newly formed Golgi-derived secretory vacuoles. Concomitantly appearing autophagosomes were, however, only labelled for cathepsin B. It is concluded that segregation of lysosomal and digestive enzymes is incomplete in normal acinar cells resulting in a colocalization in zymogen granules. In pancreatitis colocalization in secretory granules is maintained, whereas only lysosomal enzymes were sufficiently transferred into autophagic vacuoles. No indication for impaired mechanisms of molecular sorting of lysosomal and digestive enzymes in caerulein-induced pancreatitis was found.
Animals↗
Volume and enzyme kinetics of human pancreatic secretion after endogenous stimulation with the Lundh test meal.
The present study was undertaken to investigate the volume and enzyme kinetics of human pancreatic secretion, after endogenous stimulation with a Lundh test meal, and evaluate the most reliable enzyme and collection period. The prestimulatory volume rates did not differentiate normal from pathologic pancreatic function. After ingestion of the test meal, the immediate increase in volume secretion was identical in healthy subjects and patients with pancreatic insufficiency. The latter showed a drastic reduction of prestimulatory and postprandial enzyme secretion. Cimetidine taken orally 12 and 2 h before the test meal study had no effect on volume and enzyme secretion and endogenous CCK release. Especially in severe pancreatic insufficiency, this modification simplified the performance of the Lundh test. The estimation of lipase and trypsin gave a significant correlation between Lundh test and secretin-cerulein test. The endogenous stimulation by Lundh test meal is a reliable test for routine diagnostic and scientific purposes.
Adult↗