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G Adler

Publications and source records attributed to G Adler.

At least 361 records · Page 20Linked to original sources
PubMed1990

Resolution of human exocrine pancreatic juice proteins by reversed-phase high performance liquid chromatography (HPLC).

Exocrine proteins contained in human pancreatic juice were analyzed by reversed-phase high performance liquid chromatography (RP-HPLC). Pancreatic juice was saved by endoscopic retrograde cannulation of the main pancreatic duct in 17 persons: 12 without pancreatic disease, 3 patients suffering from recurrent acute pancreatitis probably due to pancreas divisum, 1 patient with a carcinoma of the pancreas, and 1 patient with chronic calcified pancreatitis. The juice proteins were separated on a silica column (Nucleosil 300-7 RP) by use of a multistep acetonitrile/water gradient (+0.1% trifluoroacetic acid). Up to 18 individual peaks could be separated by one analytical run (60 min). Molecular weight analysis by sodium dodecyl sulfate-gel electrophoresis indicated the presence of enzymes such as amylase, prophospholipase A2, procarboxypeptidases, trypsinogens, and chymotrypsinogens in certain peaks. Small residual enzymatic activities correlating with certain peaks were detected for amylase and chymotrypsin, and high residual activities were found for phospholipase A (recovery of enzymatic activity compared with the original sample amounted to 65%). Significant amounts of cathodic trypsin-like immunoreactivity were found in two certain peaks. By always loading 350 micrograms of protein/injection on the column the profiles of various samples showed similar patterns. Repeated injections of aliquots revealed highly reproducible profiles. RP-HPLC offers precise, reproducible, and rapid separation of the major proteins of human pancreatic juice.

Chromatography, High Pressure Liquid↗
PubMed1990

Pancreatic secretory responses to long-term infusions of secretin and cerulein in humans.

We measured pancreatic enzyme and bicarbonate responses to graded doses of intravenous secretin or cerulein alone or together in healthy human subjects. Bicarbonate responses were steady and well maintained during the last 3.5 h of the 4 h of infusions of secretagogues, giving evidence for a constant pancreatic flow rate. Potentiation (more-than-additive response) was observed between secretin and cerulein for bicarbonate secretion, but not for enzyme secretion. Secretin stimulated pancreatic enzyme secretion. The effect was most pronounced with amylase secretion and less prominent with lipase, trypsin, and chymotrypsin secretion. Changes in the proportion of enzymes were seen over time, with trypsin and chymotrypsin output declining towards the end of cerulein infusion. We conclude that in humans the effects of secretin on pancreatic enzyme secretion are complex and include time-dependent changes in the enzyme mixture, but potentiation between secretin and cerulein does not occur for enzyme output.

Adult↗
PubMed1990

Hormones as regulators of pancreatic secretion in man.

At the beginning of the century, Pavlov suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss & Starling published their experiments on secretin and claimed that the nervous regulation is 'superfluous and improbable'. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural, hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretion modulating the response.

Cholinergic Fibers↗
PubMed1990

Follow-up of the serum levels of extracellular matrix components in acute and chronic pancreatitis.

Time-dependent serum concentrations of extracellular matrix proteins were studied in 32 patients with pancreatitis in order to find potential markers of the reparative response during the disease. Patients were subdivided by clinical and biochemical criteria: severe acute pancreatitis (n = 10), moderate acute pancreatitis (n = 17), and acute attack of chronic pancreatitis (n = 5). Serum and plasma samples were collected on days 1-7, 10, 14, and 21 for measurements of the aminoterminal propeptide of type III procollagen (PIIINP), hyaluronic acid, laminin, fibronectin, and routine clinical-chemical parameters. During an acute attack of chronic pancreatitis all parameters were within the reference range. In moderate acute pancreatitis concentrations of PIIINP, laminin, and hyaluronic acid fluctuated around the upper reference limit, but declined to mid-normal levels at day 21. In severe acute pancreatitis all three parameters increased. In patients who died as a consequence of sepsis and multi-organ failure the increase in PIIINP, laminin and hyaluronic acid was much more pronounced and paralleled by a decrease in plasma concentrations of fibronectin. In conclusion, this study revealed a relation between the severity of acute pancreatitis and the increase in serum concentrations of extracellular matrix components, especially PIIINP.

Acute Disease↗
PubMed1990

Influence of stimulation parameters on auditory stimulus processing in schizophrenia and major depression: an auditory evoked potential study.

The influence of stimulation frequency and stimulus intensity on the auditory evoked potential components N1 and P2 was investigated in schizophrenic and major depressive patients. The findings in the patients were compared with those in normal controls. At a high stimulation frequency the amplitude of N1 was enhanced in both schizophrenic and major depressive patients; the latency of N1 increased only in the schizophrenic patients. These changes may be related to impairments of auditory input control and processing in these diseases. In the schizophrenic patients, P2 latency was prolonged under treatment with high-potency neuroleptic drugs.

Acoustic Stimulation↗
PubMed1990

Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test.

The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration.

Breath Tests↗
PubMed1990

[Paralytic ileus as an initial manifestation of malignant VIPoma of the pancreas--case report with review of the literature].

A 57-year old patient with a paralytic ileus of unknown origin was admitted to the intensive care unit. Because of the laboratory findings with therapy resistant hypokalemia, hypercalcemia and metabolic acidosis a VIPoma was suspected. Therapy with somatostatin resulted in correction of laboratory abnormalities and in normalization of gastrointestinal motility. Plasma concentrations of VIP and PP were elevated, ultrasonography revealed a pancreatic tumor. Postsurgical examination of the removal tumor tissue confirmed the diagnosis of a malignant VIPoma. Clinical symptoms, laboratory findings with and without somatostatin-therapy and immunhistochemical properties are described.

Biomarkers, Tumor↗
PubMed1990

[Ultrastructural diagnosis of neuroendocrine tumors using fine needle biopsy].

Ultrasonic-guided fine-needle-biopsies of primary pancreatic tumours or liver metastasis were performed in 13 patients with neuroendocrine tumours of the gastrointestinal tract (5 carcinoids, 3 gastrinoma, 1 PPoma, 1 calcitoninoma, 1 insulinoma, and 2 non-functional tumours). Specimens obtained were examined on the light- and electronmicroscopic level. In all cases ultrastructural examination sufficiently revealed the correct diagnosis, due to the presence of cytoplasmic neuroendocrine granules within the tumour cells. Additionally performed immunocytochemical investigations at the ultrastructural level enabled the discrimination of gastrinomas, insulinomas, and PPomas. In contrast, light-microscopic examination was less sensitive for tumour classification. It is concluded that ultrastructural investigation of fine needle biopsies represents a valuable method to sufficiently discriminate neuroendocrine neoplasms.

Adenoma, Islet Cell↗
PubMed1989

Characterization of phospholipase A2 activity in aspirates of human pancreatic pseudocysts after isolation by reversed-phase high performance liquid chromatography.

Phospholipase A (PLA) is able to attack membrane phospholipids and thereby plays a putative role in the pathogenesis of pancreatic pseudocysts. We looked for PLA2-like activity in aspirates from human pancreatic pseudocysts. In material originating from one cyst which occurred shortly after an acute pancreatitis attack, hydrolyzing enzymatic activity measured by a sensitive bioassay system for PLA2 activity was found without prior trypsin activation (67 x 10(3) U/min/100 microliters). A biochemical characterization of this hydrolyzing enzymatic activity was provided after resolution of the respective proteins contained in the cyst fluid by HPLC. High hydrolyzing activities were found in correspondence to one specific, early eluting peak. The purified enzyme had pH optima at 3.5 and 6. Addition of EDTA (5 mM) to the test system abolished the enzymatic activity which mirrored the requirement for calcium ions. The activity was optimal at calcium concentrations ranging from 1-2 mM. Higher calcium concentrations reduced the enzymatic activity. The enzyme showed high heat stability. SDS-gel analysis of the peak showed one single band with a molecular weight of about 20,000 Daltons. Our findings demonstrate the possibility of activated, PLA-like activity in human pancreatic pseudocyst fluid. We speculate that an inappropriate activation of this enzyme in peri- or intrapancreatic "fluid collections" could account for pseudocyst formation after an acute pancreatitis attack.

Calcium↗
PubMed1989

Immunocytochemical and morphometric analysis of acinar zymogen granules in human acute pancreatitis.

In the present study fine structural changes of acinar zymogen granules were investigated in human acute pancreatitis. Pancreatic tissue was obtained at surgery from 6 patients, prepared for ultrastructural analysis, and stained immunocytochemically for trypsinogen. Stereological parameters of zymogen granules were evaluated. The density of the immunocytochemical labelling for trypsinogen was estimated over zymogen granules, the rough endoplasmic reticulum, Golgi apparatus and the acinar lumina. In acute pancreatitis the number of zymogen granules was diminished and their size reduced. The density of the labelling for trypsinogen was unchanged over zymogen granules but showed a significant reduction over the rough endoplasmic reticulum, Golgi apparatus, and the acinar lumina. In general the integrity of zymogen granules was well preserved. Focally degenerative changes of zymogen granules and large autophagosomes were observed. From the immunogold labelling a disturbance of enzyme synthesis and secretion was suggested. Evidence is given that a disruption of the zymogen granule membranes and a fusion with lysosomal bodies might contribute to the pathogenesis of human acute pancreatitis.

Acute Disease↗
PubMed1989

Histochemical and ultrastructural characteristics of tubular complexes in human acute pancreatitis.

The morphologic characteristics of ductlike tubular complexes were studied in human acute pancreatitis. Pancreatic specimens were obtained from 10 patients who were operated on for acute pancreatitis. Immunocytochemistry for pancreatic enzymes, keratin, actin, and carcinoembryonic antigen were combined with lectin-binding studies and ultrastructural investigations. Irrespective of clinical onset and duration of pancreatitis, tubular complexes situated in the vicinity of fat necrosis were observed in all patients. Intermediate forms of ductlike structures were characterized by widening of acinar lumina, decreased height of acinar cells, and large autophagic vacuoles. These structures bound all of the lectins employed and retained their immunoreactivity to secretory proteins. Typical tubular complexes were composed of low cuboidal or flattened cells surrounding a large acinar lumen. They revealed a loss for pancreatic enzymes, a reduced lectin-binding for L-fucose and N-acetylgalactosamine, and an increase for cytoskeletal proteins (keratin, actin). It is concluded that tubular complexes in human acute pancreatitis represent degenerating acinar cells which lost their secretory and membrane characteristics.

Acute Disease↗
PubMed1989

Effect of atropine on feedback regulation of pancreatic secretion in rats.

In the present study the effect of atropine on feedback regulation of pancreatic function was investigated in male rats. Orogastric tube feeding of a single dose of the protease inhibitor camostate (100 mg) caused a 6-fold increase in plasma CCK. This was accompanied by a 50% decrease in pancreatic enzyme content for up to 6 h. The effect of i.v. infusion of atropine (100 micrograms.kg-1.h-1) was studied 60 and 180 min after camostate feeding. Atropine completely abolished the decrease in enzyme content 180 min after camostate feeding. The stimulated CCK plasma levels were significantly lowered by the infusion of atropine 60 min, but not 180 min, after feeding of camostate. It is discussed that a cholinergic pathway mediates CCK release in the early phase of feedback regulation of pancreatic function.

Amylases↗
PubMed1989

Effect of a low-molecular weight serine proteinase inhibitor (camostate) on amylase release from isolated pancreatic acini.

Oral administration of the proteinase inhibitor camostate to rats results in a characteristic regulation of pancreatic enzyme synthesis and release. These effects are thought to be mediated by an endogenous cholecystokinin release in answer to camostate feeding. An additional direct effect of the compound could be exerted directly on the acinar cell. We evaluated in the present study whether the acute or chronic influence of camostate alters the basal or cerulein-stimulated enzyme release from isolated rat acini. Neither basal nor cerulein-induced (10(-12) to 10(-8) M) amylase release from acini of non-pretreated donor rats were influenced in the presence of 5, 50, or 500 microM camostate. After oral feeding of camostate (200 mg/kg b.wt. daily) over 5 days pancreatic growth occurred. In experiments with acini obtained from the camostate-pretreated rats highly significant reductions of the cerulein-induced amylase release were found as compared to controls. Our findings exclude a direct effect of camostate on the secretory process of pancreatic acinar cells. However, after repeated oral pretreatment of donor rats a "desensitization" of acini against cerulein stimulation occurs. This latter effect is ascribed to elevated endogenous cholecystokinin which was released in response to camostate feeding.

Amylases↗
PubMed1989

Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion.

The present study evaluates the effect of atropine and of the cholecystokinin receptor antagonist loxiglumide on feedback regulation of basal pancreatic secretion in 6 healthy volunteers. The intraduodenal instillation of the protease inhibitor camostate reduced enzymatic activities of trypsin and chymotrypsin by 80%. This was accompanied by a strong increase in amylase and lipase output. The intravenous infusion of atropine (5 micrograms/kg.h) completely abolished the stimulatory effect of camostate on enzyme output. The infusion of loxiglumide (10 mg/kg.h) caused no changes in camostate-induced stimulation of enzyme output. Plasma levels of cholecystokinin were not altered after intraduodenal instillation of camostate whether atropine, loxiglumide, or saline were infused. We suggest that the protease inhibitor camostate, by inhibition of the enzymatic activity of trypsin and chymotrypsin, interferes with feedback regulation of basal pancreatic secretion in humans, and this mechanism is predominantly mediated by the cholinergic system.

Adult↗
PubMed1989

A unique case of intravenous injection of fungal "pancreatic" enzymes causing shock and proteolysis of haemostatic proteins.

A 20-year-old man on oral substitution of pancreatic enzymes after hemipancreatectomy injected an enzyme preparation of fungal origin intravenously after dissolving it in water. Within a few hours chills, headache, nausea and vomiting, fever of 40.8 degrees C, and shock occurred. The acute illness might have been caused by bacteremia, an anaphylactic reaction, or by direct activation of humoral or cellular mediators by the fungal enzymes. A haemostatic disturbance, particularly a drop in plasminogen, was observed. In vitro, the fungal enzyme preparation stimulated elastase release from isolated neutrophils and eliminated plasmatic inhibitors and plasminogen in normal plasma and whole blood. Human neutrophil elastase complexed to alpha 1-antitrypsin was increased in the patient's plasma, while the levels of the complexes thrombin-antithrombinIII and plasmin-alpha 2-antiplasmin, indicating recent coagulation or fibrinolysis, respectively, were not elevated. Thus, an activation of the neutrophils with release of elastase might have contributed to the observed coagulation disturbances.

Adult↗
PubMed1989

Fibroblast structure and function during regeneration from hormone-induced acute pancreatitis in the rat.

The regeneration of the rat exocrine pancreas from a hormone-induced pancreatitis was investigated. In a previous study it was shown that the [3H]thymidine labeling index of interstitial cells increases 20- to 30-fold on day 1.5 after the induction of pancreatitis. Here we show by electron microscopic autoradiography that 80% of the labeled interstitial cells are fibroblasts. Their replication, fine structure, and collagen biosynthesis was further investigated: By day 2.5 numerous mitotic figures were found, indicating an enhanced proliferative activity of fibroblasts at the early stage of pancreatic regeneration. The ultrastructural analysis revealed that many fibroblasts contain abundant cytoplasm with a well-developed rough endoplasmic reticulum, prominent Golgi complexes, and secretory granules filled with fibrillar material. In contrast, the pancreatic fibroblasts of saline-infused control animals were shown to be spindle-shaped and to contain only very little cytoplasmic organelles. The collagen biosynthesis was quantified by in vivo labeling with [3H]proline and quantification of [3H]hydroxyproline in pancreatic protein hydrolysates. The collagen biosynthesis of experimental pancreata was measured to be 15 times that of controls on days 1.5 and 2.5 after the induction of pancreatitis and to remain fourfold elevated on days 3.5 through 10.5. In pulse-chase experiments using [3H]proline as the labeled precursor for collagen, the newly synthesized collagen was shown to be degraded with a half-life of 35 h. We conclude that replication of pancreatic fibroblasts and collagen biosynthesis as well as collagen degradation play important roles in the early phase of pancreatic regeneration.

Acute Disease↗