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  • 1
    Electronic Resource
    Electronic Resource
    General and selective inhibition of pancreatic enzyme discharge using a proteinase inhibitor (FOY-305) (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 406-411 
    Details
    ISSN: 1432-1440
    Keywords: Pancreatic secretion ; Intracellular transport ; Proteinase inhibitor ; Two-dimensional gel electrophoresis ; FOY-305
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 µM 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01742297
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  • 2
    Electronic Resource
    Electronic Resource
    Monoclonal antibodies against CEA-related components discriminate between pancreatic duct type carcinomas and nonneoplastic duct lesions as well as nonduct type neoplasias (1986)
    Springer
    Virchows Archiv 408 (1986), S. 361-374 
    Details
    ISSN: 1432-2307
    Keywords: Carcinoembryonic antigen ; Monoclonal antibodies ; Pancreatic tumours ; Immunoreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of CEA and related antigens in formalin-fixed paraffin-embedded tissues of normal pancreas and different pancreatic neoplasms was studied immunocytochemically using three monoclonal antibodies (MAbs) recognizing different epitopes on CEA and related antigens. Additionally, a number of extrapancreatic malignancies were tested. The epitope recognized by MAb 250 (present on CEA and NCA 95) was expressed in all but one pancreatic ductal adenocarcinoma and ampullary carcinoma (42/43). The MAb 431 defined epitope (present only on CEA) was less frequently found (27/43). MAb 374, defining an epitope on CEA, NCA 95 and NCA 55 proved to be nearly as sensitive tive as MAb 250, but also reacted with normal duct epithelium. In contrast, MAb 250 and MAb 431 discriminated clearly between reactive duct lesions and malignant duct changes. Moreover, these MAbs differentiated between pancreatic duct carcinomas and nonduct type carcinomas as well as benign pancreatic tumours. In duct type carcinomas, the strongest staining was observed in well differentiated tumours. No discrimination was possible between pancreatic carcinomas and other adenocarcinomas of the gastrointestinal tract nor between most of the lung carcinomas and some other malignancies, specified below. MAb 250 and MAb 431 failed to react with hepatocellular carcinomas, renal cell carcinomas, carcinoids, sarcomas and melanomas. The findings suggest that paraffin-embedded tissues of pancreatic duct type carcinomas, in contrast to nonduct type tumours and normal ducts, are distinguished by the presence of a CEA and NCA 95 related epitope.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00707694
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  • 3
    Electronic Resource
    Electronic Resource
    A monoclonal antibody with binding and inhibiting activity towards human pancreatic carcinoma cells (1986)
    Springer
    Cancer immunology immunotherapy 23 (1986), S. 185-191 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The murine monoclonal antibody (MAb) BW 494 was characterized in relation to its tissue specificity, the epitope recognized, in vitro and in vivo radiolocalization and its potential to mediate antibody dependent cellular cytotoxicity (ADCC) and complement mediated cytolysis (CMC). The MAb defined carbohydrate epitope located on a 〉200 k daltons glycoprotein was mainly expressed on the majority of well differentiated adenocarcinomas of the pancreas. Furthermore, the epitope is accessible to MAb BW 494 in vivo, allowing an enrichment of radioactive antibody at the tumor site in nude mice. Additionally, MAb BW 494 is able to use human peripheral blood lymphocytes as effector cells for ADCC reactions against appropriate tumor target cells in vitro. In contrast, the antibody does not mediate human or rabbit CMC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205648
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  • 4
    Electronic Resource
    Electronic Resource
    Localisation of hyaluronate (HA) in primary tumors and nude mouse xenografts of human pancreatic carcinomas using a biotinylated HA-binding protein (1994)
    Springer
    Virchows Archiv 424 (1994), S. 7-12 
    Details
    ISSN: 1432-2307
    Keywords: Hyaluronate ; HA-binding protein ; Pancreatic adenocarcinoma ; Metastasis ; Invasion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage was used to analyze the distribution of HA in nude mouse xenografts derived from human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic adenocarcinomas. The most reproducible results for the localisation of HA were obtained using cryostat sections. When the biotinylated HA-binding protein was applied to histological sections of nude mouse xenografts, the specific staining found could be inhibited by preincubating the HA-binding protein with an excess of HA or by hyaluronidase treatment of the tissue before staining. The highest HA concentration was found at the tumor boundaries, while in the central part of the tumor staining was slight or absent. In cryostat sections of primary tumors HA was found predominantly in the connective tissue immediately around tumor cells or at the border between the tumor and normal pancreatic tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00197386
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  • 5
    Electronic Resource
    Electronic Resource
    Immunohistochemical demonstration of villin in the normal human pancreas and in chronic pancreatitis (1991)
    Springer
    Histochemistry and cell biology 95 (1991), S. 383-390 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Human pancreatic tissue was investigated by immunohistochemistry using a polyclonal antibody against the actin binding protein villin, which participates in the formation of actin filament bundles in the microvilli. In cells of the different parts of the pancreatic duct system as well as in the acinar cells villin immunoreactivity was located mainly at the apical cell surface. This was confirmed by the ultrastructural demonstration of microvilli on the surface of duct and acinar cells, which exhibited the typical actin bundles. In chronic pancreatitis the staining for villin in duct-like structures of degenerative pancreatic tissue was irregular or even absent. This correlated with the electron microscopic observation of duct-like structures known as tubular complexes composed of cells devoid of microvilli at the apical cell surface. At the light microscopical level degenerative structures without lumen and of unknown origin showed a strong staining for villin at their basal cell surface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266966
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  • 6
    Electronic Resource
    Electronic Resource
    Glycoconjugate pattern of membranes in the acinar cell of the rat pancreas (1990)
    Springer
    Histochemistry and cell biology 93 (1990), S. 319-326 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266395
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  • 7
    Electronic Resource
    Electronic Resource
    Licht- und elektronenmikroskopische Untersuchung der Langerhansschen Inseln von Nutria (Myocastor coypus), mit besonderer Berücksichtigung der neuroinsulären Komplexe (1971)
    Springer
    Cell & tissue research 113 (1971), S. 216-229 
    Details
    ISSN: 1432-0878
    Keywords: Islet of Langerhans ; Nutria ; Islet innervation ; Neuro-insular complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Das Inselorgan von Nutria (Myocastor coypus), einem wasserlebenden, pflanzenfressenden Säuger, wurde bei neugeborenen und erwachsenen Tieren licht- und elektronenmikroskopisch untersucht. 1. Bei neugeborenen Nutria ist das Inselorgan noch nicht voll ausdifferenziert, alle Stadien der Embryonalentwicklung werden angetroffen. Lichtmikroskopisch sind die Inselzellen nur spärlich granuliert; elektronenmikroskopisch gelingt der Nachweis von 2 Zelltypen nicht, da die Sekretgranula gleichartig aufgebaut sind. 2. Die Langerhansschen Inseln von erwachsenen Nutria bestehen aus gewundenen, zweizeiligen Bändern von B-Zellen, die A-Zellen liegen in der Einzahl dazwischen eingestreut. Die A∶B-Relation beträgt 1∶9. Im Feinbau ihrer Zellorganellen und Sekretgranula stimmen die Inselzellen von Nutria weitgehend mit denen des Meerschweinchens überein. 3. Die Inseln von neugeborenen und erwachsenen Tieren enthalten zahlreiche Nervenfasern und zugehörige Schwannsche Zellen, die in der Nachbarschaft der Kapillaren liegen und häufig von deren Basalmembran umhüllt sind. 4. Eine Sonderform der Zusammenlagerung von Nervengewebe und Inselgewebe stellen die neuro-insulären Komplexe, bei denen vegetative Ganglienzellen und Inselzellen in einem gemeinsamen Zellverband vereinigt sind. Die Ganglienzellen treten durch Synapsen untereinander in Verbindung, sie grenzen außerdem mit ihren Ausläufern ohne Zwischenschaltung von Bindegewebe an die Inselzellen. In dieser Grenzzone werden ebenfalls synaptische Endigungen an den Inselzellen beobachtet.
    Notes: Summary The Langerhans islet organ of Nutria has been studied in the light and electron microscopes. 1. In the pancreas of new born Nutria all stages of embryonic differentiation of the islets are still encountered. The islet cells are only scarcely granulated, and ultrastructural differentiation of two types of islet cells according to the size or density of secretory granules is not yet possible. 2. The islets in adult Nutria consist of tortuous bands of B cells with A cells scattered singly among the bands. The A∶B cell number ratio is 1∶9. The fine structural appearances of the secretory granules in A and B islet cells in Nutria correspond respectively to those of A and B islet cells in the guinea pig. 3. The islets of new born and adult Nutria contain numerous nerve fibers and associated Schwann cells, which presumably are located along the islet capillaries. Synaptic contact of nerve fibers with both types of islet cells has been encountered. 4. The close association of nerve cells with islet cells and the fine structural appearance of both elements in the neuro-insular complexes is described. Different ganglionic cells are joined by axo-somatic and axo-dendritic synapses. The incidence of synaptic contacts between nerve cells and islet cells is not greater in the neuro-insular complexes than in the islets of Langerhans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00339417
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  • 8
    Electronic Resource
    Electronic Resource
    Growth of rat pancreatic acinar cells quantitated with a monoclonal antibody against the proliferating cell nuclear antigen (1994)
    Springer
    Cell & tissue research 276 (1994), S. 603-609 
    Details
    ISSN: 1432-0878
    Keywords: Pancreas, exocrine ; Acinar cells ; Proliferation ; Proliferating cell nuclear antigen (PCNA) ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The monoclonal antibody PC10 raised against the proliferating cell nuclear antigen (PCNA) was used to study acinar cell replication in the pancreas of rats under different functional conditions. In Western blots, the antibody recognized a single band of 37 kDa in pancreatic homogenates indicating its specificity in this particular species and organ. Three conditions of growth were chosen for immunohistochemical analysis: pancreatic preand postnatal development, pancreatic regeneration after injury, and cholecystokinin-stimulated acinar cell proliferation. The time course of acinar cell replication under each condition was the same as that obtained after tritiated thymidine incorporation with subsequent autoradiography, indicating that the percentage of PCNA-positive cells reflects the pool of cycling cells in the models investigated. However, the absolute number of PCNA-positive cells was two to ten times higher than comparable labeling indices from 3H-thymidine autoradiography. This finding might reflect the half life of PCNA, which exceeds the duration of the S-phase. Thus, PCNA-positive cells not only represent S-phase cells, but also cells that have recently completed the cell cycle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00343959
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  • 9
    Electronic Resource
    Electronic Resource
    Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor (1990)
    Springer
    Cell & tissue research 262 (1990), S. 143-148 
    Details
    ISSN: 1432-0878
    Keywords: Exocrine pancreas ; Proteinase inhibitor-DNA synthesis ; Mitotic activity ; Rat(Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 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 6h. 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 μCi/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 24h 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 24h, 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00327755
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  • 10
    Electronic Resource
    Electronic Resource
    Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor (1987)
    Springer
    Cell & tissue research 247 (1987), S. 187-193 
    Details
    ISSN: 1432-0878
    Keywords: Exocrine pancreas ; Proteinase inhibitor ; Feedback regulation ; Cholecystokinin ; Fine structure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Application of a single dose of a new type of proteinase inhibitor camostate (FOY-305) via orogastric tube was used in rats to study the dose-response relationship of resulting pancreatic stimulation. Doses up to 10 mg/ kg failed to elicit any response, while significant decrease in enzyme content and increase in serum CCK-levels were observed with doses ranging from 25 to 400 mg/kg. A single dose of 100 mg/kg was selected for a time-sequence analysis, which revealed a 60 to 70% depletion of enzyme stores persisting over 6 h and reverting to control levels by 12 h. Peak increases in serum CCK-levels (15-fold above the elevation observed after regular food intake) were found after 30 min and persisted as an 8-to 10-fold elevation for at least 3 h, then declined to control levels by 9 h. This prolonged endogenous hormone release and resulting pancreatic stimulation were also verified in a separate group of animals in which volume, protein, and enzyme output were measured after cannulation of the pancreatic duct. While volume secretion was not altered by feeding a single dose of 100 mg/kg FOY-305, protein and enzyme output increased 2-to 3-fold over a period of 7 h. Fine-structural analysis of the pancreas demonstrated efficient depletion of zymogen granules from acinar cells with all doses between 50 and 400 mg/kg, accompanied by the appearance of membrane material in the acinar lumina at 3 and 6 h. The same transient increase in the number of lysosomal bodies predominantly containing mitochondria with all doses above 50 mg/kg was interpreted as increased organelle turnover due to persisting hormonal stimulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216561
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