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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 415 records · Page 23Linked to original sources
PubMed1986

Time course and cellular source of pancreatic regeneration following acute pancreatitis in the rat.

The regenerative capacity of the different cell types in the rat exocrine pancreas has been studied in a model of hormone-induced acute pancreatitis in which pancreatic edema, inflammation, and acinar cell destruction were induced within 12 h of infusion of supramaximal concentrations of cerulein (5 micrograms/kg/h). A sequential biochemical and structural analysis of the pancreas in daily intervals was combined with the autoradiographic quantitation of labeling indices of five cell populations following 3H-thymidine injection at days 1-7 after induction of pancreatitis. Desquamation of acinar cell apical cytoplasm and release of cytoplasmic segments into the acinar lumen on the first day following induction of pancreatitis led to formation of duct-like tubular complexes. Enzyme content in the pancreas decreased progressively following the formation of the edema to levels 15-20% of controls and remained reduced during the initial 5 days. Thymidine incorporation into total DNA showed a biphasic pattern with a distinct peak at day 1 and a second broader peak between days 4 and 7. Autoradiographic quantitation of labeling indices demonstrated the exclusive incorporation into intercalated duct cells and interstitial cells during the initial 24 h, while the second peak was predominantly due to labeling of acinar cells. Larger interlobular ducts and islets did not show changes in labeling index. In vivo labeling with 3H-thymidine during the first day and analysis of labeling indices 14 days later showed the persistence of label in intercalated duct cells and interstitial cells and argued against the stem cell hypothesis and against transformation of duct cells into acinar cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate).

The serine proteinase inhibitor camostate was fed to rats in single, daily doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg for 5, 10, or 15 days. Within 5 days, pancreatic size and protein, DNA, and enzyme content increased significantly. After prolonged administration, this trophic effect was more pronounced, and anticoordinate regulation of the synthetic rate of individual secretory proteins was observed. While enzyme content and protein synthesis of trypsinogen and chymotrypsinogen were increased, respective values for amylase were drastically reduced. Plasma levels of cholecystokinin (CCK) did not differ from controls when measured 24 h after administration of camostate. Immediately after oral feeding of camostate, CCK levels increased 10-fold above controls, reached a maximum after 90 min, and remained elevated for more than 6 h. Proglumide, a CCK-receptor antagonist, only slightly reduced the trophic action of the proteinase inhibitor. The data indicate that endogenous CCK release by a proteinase inhibitor is as potent in the modulation of pancreatic growth and individual enzyme synthesis as exogenous hormone application.

Animals↗
PubMed1986

Psychotherapy of the narcissistic personality disorder patient: two contrasting approaches.

The differences in the theoretical and clinical approaches that Kernberg and Kohut have defined are used to discuss the psychodynamics and psychotherapy of the narcissistic personality disorder patient. Their contrasting contributions help clarify the nature of these patients' difficulties, the possibility that there is a spectrum of narcissistic disorders, the effect of existing theory and the personalities of clinicians-theoreticians on the collection of clinical data, and the effects of theoretical formulations on the psychotherapeutic process.

Attitude of Health Personnel↗
PubMed1986

[Differential diagnostic evaluation of chronic pancreatitis in relation to pancreatic cancer based on clinical, laboratory chemical and diagnostic parameters. Studies of 174 patients in 10 years].

174 patients with chronic pancreatic diseases, 30 patients with pancreatic carcinoma and 144 with chronic relapsing pancreatitis, 50 of them with calcifications, were observed in the Department of Internal Medicine of the University of Marburg/FRG between 1972 and 1982. In order to differentiate between carcinoma and relapsing pancreatitis the data of these patients were analysed retrospectively with regard to patient history, actual complaints, findings of laboratory, sonography, ERCP and X-ray investigations. The following results were obtained: Of discriminating value are steatorrhoe, local palpatory pain, alcohol ingestion, a history of earlier attacks and relapsing pain situations; however, general abdominal pain, nausea, vomiting and weight loss (if not exactly specified) are not. Within the laboratory findings bilirubin, GOT, alkaline phosphatase, gamma-GT, serum potassium, blood sugar and chymotrypsin content of the stool were significant while serum and urine amylase were similarly distributed within the groups of patients. Carcinoma and chronic relapsing pancreatitis can be identified by sonography in the majority of patients, but calcifications of the pancreas were rarely demonstrated during this observation period. The obstruction of the extrahepatic bile ducts--mostly due to a carcinoma of the pancreas head--was usually well documented by sonography. Intraabdominal air proofed to be the most disturbing factor. In carcinoma patients, the ERCP is important in demonstrating a complete obstruction of the pancreatic duct and stenosis and dilatation of the extrahepatic bile ducts. In patients with chronic relapsing pancreatitis the pancreatic duct alterations such as dilatations and partial stenosis are well documented by ERCP especially if calcifications occur. In patients without calcifications, dilatation of the branches of the main duct are less relevant in the diagnosis of pancreatic diseases. Radiological demonstration of calcification of the pancreatic area is important for the differential diagnosis. Longstanding characteristical complaints, symptoms and calcifications within the pancreatic area are the most relevant factors in discriminating carcinoma and chronic relapsing pancreatitis.

Adult↗
PubMed1985

Cell membrane coating with glutaraldehyde: application to a versatile solid-phase assay for thyroid membrane proteins and molecules interacting with thyroid membranes.

In defined conditions, glutaraldehyde was shown to tightly bind cell membranes to flexible microtiter plates without significant alteration of the antigenic and functional properties of membrane proteins. In the presence of 0.06% glutaraldehyde, human thyroid membranes were bound to plastic firmly enough to resist numerous washing and flicking steps; the coated membranes remained almost unaltered with regard to monoclonal antibody and thyrotropin binding as well as adenylate cyclase and peroxidase activities. Based on the use of thyroid membrane-coated microtiter plates, a versatile solid-phase assay was developed which allowed screening of anti-membrane monoclonal antibodies, detection of thyrotropin-displacing activity in hormone and antibody preparations, and monitoring of fractionation experiments of solubilized membrane antigens and thyrotropin receptor. It was concluded that the use of glutaraldehyde for coating cell membranes to flexible microtiter plates enabled the establishment of simple, rapid, and reliable assays for detection and quantitation of membrane proteins and molecules interacting with membranes.

Adenylyl Cyclases↗
PubMed1985

Atypical mycosis fungoides with cerebral involvement.

This report concerns a 17-year-old male patient with atypical mycosis fungoides (m.f.). Initial examination revealed generalized lymphoma and uncharacteristic livid skin efflorescence. The patient developed bone marrow involvement and meningeal leukaemia 6 months later. Diagnosis was confirmed by immunohistochemistry and electron microscopy. Aggressive chemotherapy yielded no response.

Adolescent↗
PubMed1985

Cerulein-induced pancreatitis in rats: increased lysosomal enzyme activity and autophagocytosis.

The involvement of lysosomes in the normal secretory process of the exocrine pancreas and in the onset of acute, hormone-induced pancreatitis was studied. The enzymatic activities of cathepsin B and beta-galactosidase were determined in the pancreas of rats that had been stimulated by either maximal (0.25 microgram X kg-1 h-1) or supramaximal (5 micrograms X kg-1 h-1) concentrations of cerulein. Maximal stimulation led to a moderate increase in cathepsin B activity and the ultrastructural appearance of multivesicular bodies. Supramaximal stimulation resulted in formation of large cytoplasmic vacuoles and progressive destruction of acinar cells which was paralleled by a marked increase of lysosomal enzyme activity.

Amylases↗
PubMed1985

Structural and biochemical characterization of maximal and supramaximal hormonal stimulation of rat exocrine pancreas.

To study the regulation of the successive steps along the secretory pathway in the rat exocrine pancreas the model of in vivo infusion of synthetic caerulein in conscious rats for periods up to 72 h was combined with electron microscopy and in vitro analysis of protein synthesis, intracellular protein transport and enzyme discharge using isolated pancreatic lobules. Prolonged and maximal hormonal stimulation was obtained with 0.25 microgram kg-1 h-1 caerulein and resulted in a 80-90% depletion of enzyme stores within 1 to 3 h, followed by coordinate and anticoordinate changes in individual rates of (pro-)enzyme synthesis after a lag period of 3 h. One group (two amylases) revealed a decrease in synthesis to levels about 10-fold lower than controls. A third group of proteins (one trypsinogen, lipase, proelastase) did not show changes in synthesis with hormone stimulation. The sum of such alterations led to an increase in total rate of synthesis after 6 h, which was combined with acceleration of intracellular transport, packaging, and granule discharge, thus enabling a sustained rate of secretion over the period of stimulation. In contrast, infusion of a supramaximal dose of caerulein (5.0 micrograms kg-1 h-1) induced acute edematous pancreatitis and led to an almost complete reduction of volume and protein output from the cannulated main pancreatic duct. 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 led to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fused with the lateral instead of the apical plasma membrane, discharging their content into the interstitial space. Vacuole formation was associated with activation of lysosomes and with cytoplasmic destruction of acinar cells. The findings indicated severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of caerulein, which finally resulted in autodigestion of the pancreas.

Amino Acids↗
PubMed1985

Failure of secretin to prevent or ameliorate cerulein-induced pancreatitis in the rat.

Infusion of supramaximal concentrations of the synthetic pancreozymin analog cerulein induces acute edematous pancreatitis in the rat. Vacuolization and necrosis of acinar cells is paralleled by an almost complete reduction of pancreatic secretion from the cannulated duct. Preinfusion or coinfusion of synthetic secretin slightly increases pancreatic volume and protein secretion. This effect is only transient, and is always overcome by the actions of cerulein. Secretin does not prevent or improve the cellular destruction of the acinar cells. The results suggest that secretin has no beneficial effect on hormone-induced pancreatitis.

Amylases↗
PubMed1984

General and selective inhibition of pancreatic enzyme discharge using a proteinase inhibitor (FOY-305).

The guanidino acid esters (FOY, FOY-305) represent a new class of potent proteinase inhibitors and are thought to have a beneficial effect on the course of acute pancreatitis. Because of their structure and low molecular size they might enter cells and interfere with cellular processes. To test this possibility in the case of the exocrine pancreas a series of in vivo and in vitro studies was carried out to analyse intracellular transport and discharge of pancreatic enzymes in the presence of FOY-305. The infusion of FOY-305 to conscious rats led to a transient inhibition of protein and enzyme discharge from the cannulated pancreas accompanied by lower serum enzyme levels and increased enzyme content in the pancreas. An identical inhibition of discharge of newly synthesized proteins was observed in vitro in the presence of 1 microM FOY-305. The analysis of the release of individual enzymes using separation on two-dimensional gels showed a pronounced inhibition of mainly the release of acidic proteins. FOY-305 not only interfered with discharge of serine proteinases (trypsinogen, chymotrypsinogen, proelastase) but also with procarboxypeptidases and lipase. It was concluded that FOY-305 enters the acinar cell and due to an unspecific binding to acidic proteins interferes with the intracellular transport of individual enzyme proteins during their passage through the membrane-bound cellular compartments. This charge-dependent effect is independent of the inhibitory effect on enzymatic activity of serine proteinases.

Amylases↗
PubMed1984

Effects of bile salts on permeability and morphology of main pancreatic duct in cats.

We studied the changes in permeability and morphology in the main pancreatic duct of cats after exposure of the duct to specific bile salts. Cats were anesthetized and the main pancreatic duct was cannulated in the tail and head of the pancreas. The duct was perfused with sodium cholate (1, 1.5, 2, 15 mM) or sodium glycodeoxycholate (1, 2, 15 mM) for 60 min at pressures which never exceeded 20 cm water. Then the duct was perfused with fluorescein-tagged dextran molecules of specific size (3000, 20,000, or 40,000 daltons). Recovery of the dextran from portal venous blood indicated that the duct was permeable to that particular dextran. Normally the ducts were impermeable to even the 3000-dalton dextran, and perfusion with either 1 mM cholate or glycodeoxycholate did not change this. However, perfusion with either bile salt at concentrations above 1 mM progressively increased duct permeability. At this highest bile salt concentrations used, the ducts became permeable to molecules as large as 20,000 daltons. Morphologic changes paralleled the changes in permeability. Control animals had pancreatic ducts whose ultrastructure was indistinguishable from normal. Perfusion of the ducts with low concentrations of bile salt for up to 60 min resulted only in a loss of microvilli from the cell surface and an increase in cytoplasmic phagolysosomes. Perfusion with higher concentrations of bile salt for 5-60 min induced progressively severe alterations. These included disruption of the tight junctions and the swelling of intercellular spaces between the duct cells, flattening of the duct epithelium, and eventual cell loss which left a break in the epithelial lining of the duct. These studies indicate that the pancreatic duct in cats, exposed to specific bile salts at physiological concentrations and pressures, undergoes marked structural alterations. The duct becomes permeable to molecules at least as large as 20,000 daltons, whereas it is normally impermeable to molecules as small as 3000 daltons.

Animals↗
PubMed1984

Erythrocyte membrane alterations as the basis of chlorate toxicity.

The effects of sodium chlorate and of sodium nitrite on human erythrocytes were studied in vitro. Nitrite rapidly oxidised haemoglobin and glutathione; reduction of methaemoglobin (Hbi) by methylene blue was complete during 3 h of incubation with nitrite. With chlorate, a concentration-dependent lag phase was seen before Hbi was formed. After prolonged incubation, Hbi could no longer be reduced with methylene blue. Several other effects were observed that explain the clinical picture of chlorate poisoning which involves haemolysis followed by disseminated intravascular coagulation and renal failure: increased permeability to cations, increased resistance to hypotonic haemolysis and prolonged filtration time through polycarbonate membranes with cylindrical pores of 5 micron diameter. This suggests an increased membrane rigidity due to membrane protein polymerisation, as demonstrated by SDS polyacrylamide gel electrophoresis. Simultaneously, erythrocyte enzymes were inactivated, primarily glucose-6-phosphate dehydrogenase which is necessary for the therapeutic effect of methylene blue. This explains the inefficacy of methylene blue in the treatment of a case of chlorate poisoning that we observed (Arch. Toxicol., 48 (1981) 281).

Chlorates↗
PubMed1984

Simple and sensitive method for estimation of antithyroid plasma membrane antibodies in the serum of patients with autoimmune thyroid diseases; comparison with other assays.

The ability of protein A from Staphylococcus aureus to interact with Fc fragments of IgG was used to estimate the antithyroid plasma membrane antibodies in sera of patients with Graves' disease. The results were expressed as an antithyroid plasma membrane antibodies (ATMA) index. The ATMA index estimated in 60 healthy blood donors varied from 0.57 to 1.28, with a mean value of 0.99, SD theta 0.20. The ATMA index in hyperthyroid untreated Graves' disease varied from 1.80 to 8.0, with a mean value of 4.7. Autoantibody binding to thyroid plasma membranes could be inhibited by (Fab)2 fragments obtained from the serum of patients with Graves' disease but not by (Fab)2 fragments obtained from the serum of healthy blood donors. The influence of rabbit antithyroglobulin and antimicrosomal antibodies on the ATMA index estimation has been evaluated. The ATMA index estimation was compared with the thyrotrophin binding inhibiting immunoglobulins (TBII) index and with the adenyl cyclase stimulating activity of immunoglobulins obtained from 92 hyperthyroid Graves' patients. The ATMA index was positive in 97%, the TBII index in 62% and TSI in 35% of cases. This method using protein A could also be used for estimation of ATMA in other autoimmune thyroid disorders.

Autoantibodies↗
PubMed1984

Secretagogue-induced membrane alterations in dispersed acini from rat pancreas.

Dispersed acini from rat pancreas were used to examine the effects of various pancreatic secretagogues on the fine structure of the acinar cell plasma membrane. With the C-terminal octapeptide of cholecystokinin, the C-terminal tetrapeptide of cholecystokinin, carbamylcholine, bombesin, A23187, vasoactive intestinal peptide or 8-bromo cyclic adenosine monophosphate, concentrations of the secretagogues that caused maximal stimulation of enzyme secretion did not produce alterations of the acinar cell plasma membrane. Supramaximal concentrations of the C-terminal octapeptide of cholecystokinin, the C-terminal tetrapeptide of cholecystokinin or carbamylcholine induced the formation of cytoplasmic protrusions at the basolateral plasma membrane of the pancreatic acinar cell, whereas supramaximal concentration of bombesin, A23187, vasoactive intestinal peptide or 8-bromo cyclic AMP did not alter the morphology of the acinar cell. Effects of the C-terminal octapeptide of cholecystokinin could be detected as early as after two minutes of incubation and these effects progressed for up to 30 minutes of incubation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Effects of in vivo cholinergic stimulation of rat exocrine pancreas.

Peptide and cholinergic secretagogues both produce biphasic dose-response curves for pancreatic enzyme secretion in vitro: supraoptimal doses result in submaximal secretory responses. We compared the effects of maximal and supramaximal doses of a cholinergic agent (carbachol) on rat exocrine pancreas in vivo. In conscious rats, volume and enzyme output were measured from the cannulated pancreatic duct during infusion of carbachol for 3 h. Infusion of 5 X 10(-7) mol . kg-1 . h-1 carbachol caused optimal stimulation, whereas a supraoptimal dose (5 X 10(-6) mol . kg-1 . h-1) resulted in submaximal response. Similar results were achieved when discharge of amylase and protein synthesis was determined in vitro after carbachol in vivo. Supraoptimal doses of carbachol increased serum amylase and enhanced acinar cell lysosomal activity in the Golgi area. The latter appeared to induce fusion of zymogen granules, which resulted in cytoplasmic vacuoles. The in vivo results corroborate in vitro findings of a biphasic dose-response relationship for carbachol and demonstrate destructive effects of supraoptimal concentrations on target cells.

Amylases↗
PubMed1983

The Sustaining Fantasy Questionnaire: measurement of sustaining functions of fantasies in psychiatric inpatients.

The concept of the sustaining fantasy and the Sustaining Fantasy Questionnaire (SFQ), an instrument for its measurement, is introduced. Sustaining fantasies represent characteristic ways to ameliorate intense negative affect or to restore self-esteem. The responses of 134 psychiatric inpatients were used to construct ten scales. The SFQ and MMPI were then administered to 125 nonpatients. Psychiatric inpatients had higher scores than normals on fantasies of death, withdrawal, restitution, suffering, God, and closeness. Fantasies of power and revenge, admiration of self, competition and aesthetics did not differentiate between groups. SFQ scales correlated significantly with MMPI scales and demographic characteristics as well with staff ratings of the inpatients.

Adult↗