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  • 1
    Electronic Resource
    Electronic Resource
    Course and spontaneous regression of acute pancreatitis in the rat (1979)
    Springer
    Virchows Archiv 382 (1979), S. 31-47 
    Details
    ISSN: 1432-2307
    Keywords: Pancreatitis ; Regeneration ; Secretory process ; Mitotic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat exocrine pancreatic function was studied structurally and biochemically after the in vivo production of acute interstitial pancreatitis by supramaximal stimulation with caerulein. Two major phases in the reaction of the gland were observed: During the first two days after cessation of the supramaximal stimulation a progressive infiltration of the interstitium and the pancreatic tissue with polymorphonuclear leucocytes, lymphocytes and macrophages occurred which led to further destruction of the gland and to decreased functional response. From two days after the cessation of the treatment, hypertrophy of centro-acinar cells and an increased rate of mitotic activity indicated regeneration of the pancreas. This was combined with an accelerated in vitro discharge of newly synthesized proteins over a period of four days. Between days three and six after the initial treatment mitotic activity was also observed in fully differentiated exocrine cells. Total structural and functional recovery of the pancreas was achieved nine to twelve days after the cessation of the supramaximal stimulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01102739
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  • 2
    Electronic Resource
    Electronic Resource
    Immunocytochemical and morphometric analysis of acinar zymogen granules in human acute pancreatitis (1989)
    Springer
    Virchows Archiv 415 (1989), S. 115-124 
    Details
    ISSN: 1432-2307
    Keywords: Human acute pancreatitis ; Zymogen granules ; Acinar cells ; Electron microscopy ; Immunocytochemistry ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00784348
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  • 3
    Electronic Resource
    Electronic Resource
    Studies on intracellular transport in the rat exocrine pancreas (1975)
    Springer
    Virchows Archiv 367 (1975), S. 289-305 
    Details
    ISSN: 1432-2307
    Keywords: Pancreas ; Protein synthesis ; Secretion ; Amino acids ; Paracrystals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vitro incubation of rat pancreatic lobules in the presence of 10 mM concentrations of 2 natural (phenylalanine, tryptophane) and 2 modified aromatic amino acids (p-fluorophenylalanine, p-chlorophenylalanine) induces paracrystal formation in the cisternal space of the rough endoplasmic reticulum and in the acinar lumen. Aggregation of secretory material in transitional elements of the rough endoplasmic reticulum suggests tubular connection to the Golgi complex. Paracrystal formation is correlated with a disturbance of the three major phases in the secretory process of the exocrine cell. Incorporation of radioactive amino acids into proteins is inhibited by 10 mM concentrations of phenylalanine and tryptophane by 20 and 50% respectively and by p-chlorophenylalanine at 1 and 10 mM concentrations by 50 and 75%. The inhibition of protein synthesis is not due to a reduced intracellular concentration of radioactive precursor amino acids. Intracellular transport of newly synthesized proteins as studied by a radioassay for zymogen discharge and by cell fractionation is similarly inhibited by phenylalanine, tryptophane and p-chlorophenylalanine at 10 mM concentrarions (20, 30, and 40% respectively). Discharge of zymogens as measured by the secretion of amylase stimulated with 5 × 10−6 M carbamylcholine is reduced by 20% if 10 mM concentrations of phenylalanine, tryptophane or p-chlorophenylalanine are present in the medium. Paracrystals were isolated by differential centrifugation and their protein content compared with isolated zymogen granules. On sodium dodecylsulfate gel electrophoresis paracrystalline proteins show the same electrophoretic pattern as the content of zymogen granules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01239337
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  • 4
    Electronic Resource
    Electronic Resource
    Studies on intracellular transport of secretory proteins in the rat exocrine pancreas (1975)
    Springer
    Virchows Archiv 368 (1975), S. 309-327 
    Details
    ISSN: 1432-2307
    Keywords: Exocrine pancreas ; Intracellular transport ; Colchicine ; Vinblastine ; Hexylene glycol ; Cytochalasin B ; Paracrystals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible role of microtubules and microfilaments in the secretory process of the rat exocrine pancreas was analysed in vitro using isolated pancreatic lobules. Colchicine and vinblastine as microtubule inhibitors, hexylene glycol as a microtubule stabilizer, and cytochalasin B as a disruptive agent for microfilaments were used in increasing concentrations to test their effects on protein synthesis, intracellular transport, zymogen discharge, and cellular respiration. Colchicine only at 10−2 M concentrations inhibits protein synthesis, while vinblastine inhibits at 10−6 and 10−5 M by 20% and at 10−4 M by 55%. A similar inhibition is observed with 1.5% concentrations of hexylene glycol while cytochalasine B at 1,5 and 10 μg/ml is without effect on protein synthesis. Colchicine and vinblastine have their major effects on intracellular transport both in secretion studies and cell fractionation experiments. Colchicine in concentrations between 10−3 to 10−5 M inhibits discharge of newly synthesized proteins by 50%, while vinblastine shows a dose-response relationship of 40% inhibition at 10−6 M to 90% at 10−4 M. Discharge of amylase is uniformly reduced by 30% by both colchicine and vinblastine in the whole dose range. The pronounced effect of colchicine and vinblastine is evident in cell fractionation studies: both drugs inhibit the disappearance of protein radioactivity from microsomes and its appearance in zymogen granules; similarly the peak radioactivity in smooth microsomes (Golgi) appears delayed. No differential effect on the secretory process was observed with 1.5% concentrations of hexylene glycol or cytochalasin B at 1.5 and 10 μg/ml concentrations. A fines tructural analysis of microtubules and microfilaments in the exocrine pancreatic cell reveals their distribution in all parts of the cytoplasm and in relation to all cell organelles. Both systems (microtubules, microfilaments) seem to be connected, at least in certain areas of the cytoplasm and at the plasma membrane. The reduction of transport efficiency by microtubule inhibitors results in a deposition of secretory material in the cisternal space of the rough endoplasmatic reticulum, which leads to the formation of paracrystals. Colchicine at 10−3 M concentrations leads to an enlargement of condensing vacuoles in the Golgi complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432309
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  • 5
    Electronic Resource
    Electronic Resource
    Human acute pancreatitis: Its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells (1986)
    Springer
    Virchows Archiv 409 (1986), S. 791-803 
    Details
    ISSN: 1432-2307
    Keywords: Human acute pancreatitis ; Enzyme immunocytochemistry ; Ultrastructure ; Acinar cell degranulation ; Fat necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human acute pancreatitis results from an autodigestive process frequently associated with alcohol abuse, gall stone disease and shock. Peripancreatic fat necrosis was identified as one of the earliest visible lesions, whereas acinar cell necrosis and haemorrhage were regarded as secondary changes. To examine the alterations in acinar cells in more detail, their enzyme content and fine structural features were studied immunocytochemically using antisera against α-amylase, lipase, trypsin, chymotrypsin and pancreatic stone protein, and electronmicroscopically in pancreatic tissues from patients with severe acute pancreatitis. Peripheral acinar cells in the immediate vicinity of fat necrosis were found to be heavily degranulated, while acinar cells at some distance of necrosis fully retained their enzyme content. Other frequent changes of the acinar cells included cuboidal transformation, loss of microvilli, increased occurrence of autophagosomes, and formation of enlarged acinar lumina. As there was no apparent cell membrane leakage or rupture of duct lumina, it is concluded that the acinar cells adjacent to fat necrosis release their granules by undirected basolateral extrusion. The findings thus suggest that one of the basic defects in acute pancreatitis is the uncontrolled release of enzymes from peripheral acinar cells into the interstitial space which, in turn, presumably by the action of lipase, leads to autodigestive fat necrosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710764
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  • 6
    Electronic Resource
    Electronic Resource
    Studies on intracellular transport of secretory proteins in the rat exocrine pancreas (1975)
    Springer
    Virchows Archiv 368 (1975), S. 329-345 
    Details
    ISSN: 1432-2307
    Keywords: Exocrine pancreas ; Secretory process ; Cobalt ; Lanthanum ; Intracellular transport ; Secretion granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of cobalt and lanthanum on the secretory process of the rat exocrine pancreas was studied in vitro using isolated pancreatic lobules. Cobalt in concentrations between 10−3 to 10−5 M has no effect on the rate of protein synthesis, intracellular transport, or discharge of zymogen granules, if the total population of stored granules is considered. It has, however, a marked effect on the release of newly packed zymogen granules which are formed during incubation in 10−3 M CoCl2. Determination of specific radioactivity in amylase released under the stimulation of 5×10−6 M carbamylcholine and of total proteins retained in the zymogen granule fraction during stimulation indicate that granules formed during incubation in CoCl2 are excluded from discharge. Lanthanum, on the other hand, has a differential effect on protein synthesis, intracellular transport, and discharge. Incorporation of tritiated leucine into TCA-precipitable proteins is inhibited by 50% at 10−3 M LaCl3. Intracellular transport as studied by cell fractionation is not changed during the first 35 min post pulse but is delayed from then on. This late effect is more pronounced if pancreatic lobules are preincubated for 60 min in 10−3 M LaCl3. Discharge of amylase and newly synthesized proteins is inhibited dose-dependently up to 80% by 10−3 M LaCl3. The effects of both cobalt and lanthanum are not due to an inhibition of cellular respiration. Comparison of these results with the inhibitory action of antimycin A between 10−4 to 10−8 M concentrations reveals a dose-dependent diminution of the rate of protein synthesis and intracellular transport, while discharge of granules is less energy dependent. The fine structural appearance of pancreatic lobules after 3 hrs incubation in 10−3 M CoCl2 is not altered, while in 5×10−3 and 10−3 M lanthanum acinar lumina are enlarged and the apical cytoplasm contains large vacuoles. At the highest concentration of lanthanum a flocculent electron dense material is observed apposed to the external lamina of the plasma membrane. The distribution of this material on the membrane is described. Antimycin A leads to callular changes corresponding to the irreversible inhibition of cellular respiration. It is concluded from the results that cobalt acts on the process of granule formation inside the cell, while lanthanum by its binding to the plasma membrane may alter molecules involved in secretagogue binding and transport systems into the cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432310
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  • 7
    Electronic Resource
    Electronic Resource
    Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue (1977)
    Springer
    Virchows Archiv 373 (1977), S. 97-117 
    Details
    ISSN: 1432-2307
    Keywords: Exocrine pancreas ; Pancreatitis ; Secretory process ; Interstitial oedema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Conscious rats were infused via a jugular vein catheter with 5×10−6 g/kg/h caerulein for periods up to 24 h. On macroscopic inspection a progressive interstitial oedema is seen to develop in the pancreas, from one hour of infusion on and is most marked at twelve hours. This oedema is largely reabsorbed after 24 h treatment, but the pancreas is considerably indurated by this time. Serum amylase levels increase consistently to reach a tenfold elevation above controls after three, six or twelve hours infusion. Premature fusion of condensing vacuoles and secretory granules leads to formation of large vacuoles in the cytoplasm of exocrine pancreatic cells. These vacuoles fuse with the lateral and basal plasma membrane and realease their content into the extracellular space. Regular discharge of zymogen granules at the cell apex into the duct system does not occur. Vacuole formation is associated with cytoplasmic destruction of the pancreatic cells. The rate of protein synthesis decreases consistently as a result of these structural alterations and this change corresponds largely to a reduction of cellular respiration. Release of amylase from isolated pancreatic lobules of caerulein infused animals shows a progressive increase of unstimulated discharge, while in vitro stimulation with 5×10−6 M carbamylcholine gives secretion patterns of wash-out kinetics. Stimulated discharge of labeled secretory proteins indicates a progressive reduction in the in vitro sensitivity of the pancreatic cells to secretagogues. After 24 h infusion of 5×10−6 g/kg/h caerulein the pancreatic lobules are totally insensitive to the in vitro effect of carbamylcholine or caerulein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432156
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  • 8
    Electronic Resource
    Electronic Resource
    Alteration of membrane fusion as a cause of acute pancreatitis in the rat (1982)
    Springer
    Digestive diseases and sciences 27 (1982), S. 993-1002 
    Details
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01391745
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  • 9
    Electronic Resource
    Electronic Resource
    Studies on intracellular transport of secretory proteins in the rat exocrine pancreas (1976)
    Springer
    Cell & tissue research 170 (1976), S. 203-219 
    Details
    ISSN: 1432-0878
    Keywords: Exocrine pancreas ; Intracellular transport ; Cell fractionation ; Enzyme discharge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The previous finding that intracellular transport of secretory proteins in the rat exocrine pancreas is accelerated by in vivo stimulation with a pancreatic secretagogue has been further analyzed. Using a radioassay for discharge of newly synthesized proteins, the rate of release was compared in control and prestimulated lobules. In control preparations discharge occurred with an initial lag period of 30 minutes and a maximum after two hours of incubation. After in vivo infusion of 5 × 10-8 g/hr. caerulein for 24 h in vitro discharge started after 10 minutes of in vitro incubation and attained a maximal rate after one hour. Using the same radioassay and several inhibitors of intracellular transport and granule discharge, it could be demonstrated that both processes were reduced to the same extent in controls and in lobules with accelerated transport. To obtain direct evidence for the degree of acceleration of the different transport steps between rough endoplasmic reticulum, Golgi complex and zymogen granules, the respective subcellular fractions of these organelles prepared and characterized ultrastructurally and biochemically. The rate of disappearance of newly formed proteins from rough microsomes and the appearance in smooth microsomes and zymogen granules were significantly increased after in vivo stimulation. The data substantiate an acceleration of the regular transport steps by the secretagogue. There was no indication that a high level of secretory activity leads to a rerouting of secretory proteins or to an omission of one of the regular steps in intracellular transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00224299
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  • 10
    Electronic Resource
    Electronic Resource
    Studies on secretory glycoproteins in the rat exocrine pancreas (1976)
    Springer
    Cell & tissue research 175 (1976), S. 227-243 
    Details
    ISSN: 1432-0878
    Keywords: Exocrine pancreas ; Golgi complex ; Glycoproteins ; Intracellular transport ; Secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using a double-label technique on isolated rat pancreatic lobules, the rate of synthesis and discharge of regular and fucosylated secretory proteins was studied under control conditions and after in vivo prestimulation with caerulein. Both labeled leucine and fucose were incorporated into pancreatic proteins at a linear rate, which was potentiated by in vivo stimulation. In pulse-chase experiments both regular and fucosylated secretory proteins were discharged into the medium in parallel. The in vivo pretreatment with caerulein caused an earlier discharge and increased the total amount released. Kinetic analysis of unstimulated (baseline) discharge of both classes of secretory proteins indicated a striking in vitro sensitivity by the previous in vivo treatment with caerulein. The biochemical data were compared to the fine structure of the Golgi complex under both control and prestimulated conditions. The Golgi stacks were composed of four to six individual cisternae which in some cases were connected by intercisternal pores. Transporting vesicles were observed fusing along the total length of the outermost cisterna on both the cis- and transside and with the lateral ends of the intermediate cisternae. Under control conditions only the last trans-cisterna contained some electron opaque material; in vivo prestimulation led to distension and filling of all cisternae in an individual Golgi-unit. Numerous stages of transformation of the last transcisterna into condensing vacuoles were observed, lending support to the hypothesis that during packaging of secretory products the membranes of the Golgi complex undergo a continuous turnover.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232080
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