[Significance of ras mutations in pancreatic diseases].
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Cell Transformation, Neoplastic↗
Biomedical subjects
S Liebe
Publications and source records attributed to S Liebe.
Cu/Zn-SOD in human pancreatic tissue and pancreatic juice.
CONCLUSION: Cu/Zn-SOD is present in pancreatic juice and tissue. Immunohistochemical studies reveal a localization of this enzyme in islet, duct, and centroacinar cells, but to a much lower extent in pancreatic acinar cells. BACKGROUND: It is generally accepted that oxygen radicals are involved in the pathogenesis of acute and chronic pancreatitis. An imbalance of radical-generating and radical-scavenging processes is thought to lead to the damage of pancreatic acinar cells that initiate the autodigestion of the whole organ. METHODS: We investigated the distribution pattern of the cytosolic radical-scavenging enzyme, copper/zinc-superoxide dismutase (Cu/Zn-SOD), in pancreatic juice and tissue. In patients with chronic pancreatitis or pancreatic malignancies, Cu-Zn-SOD was quantitated in different fractions of pancreatic juice by means of an enzyme immunoassay using two Cu/Zn-SOD-specific monoclonal antibodies. Cryostat or paraffin sections of pancreatic tissue were analyzed by immunohistochemical techniques. RESULTS: We found this enzyme to be present in the first secretin-triggered fraction of endoscopically obtained pancreatic juice in concentrations similar to serum. In contrast, after cholecystokinin stimulation, only low levels could be found in pancreatic juice, indicating that this enzyme is not actively secreted. Interestingly, pancreatic juice of patients with chronic pancreatitis or pancreas tumor contained higher levels (25-29 ng/mL) of Cu/Zn-SOD than juice of controls without pancreatic diseases (15 ng/mL). Immunohistochemical studies of Cu/Zn-SOD in pancreatic tissue revealed a more intense staining of duct cells, islet cells, and centroacinar cells, whereas acinar cells showed almost no staining for Cu/Zn-SOD.
Adult↗
Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride.
BACKGROUND & AIMS: Regulatory mechanisms in chronic pancreatitis finally resulting in pancreatic fibrosis cannot be studied sufficiently in human pancreas. Results of a new pancreatitis model in rats suitable for investigation of the processes leading to pancreatic fibrosis are presented. METHODS: Experimental pancreatitis was induced by intravenous application of 8 mg/kg body wt dibutyltin dichloride. Pancreatitis was characterized by histology, serum parameters, and immunohistochemistry, detecting inflammatory cells. Gene expression of collagen type I and transforming growth factor beta1 was shown by Northern blot analysis. RESULTS: Dibutyltin dichloride induced an acute edematous pancreatitis within 24 hours. Extensive infiltration with mononuclear cells could be observed after day 7 followed by the development of fibrosis. Parallel to the cell infiltration, an upregulation of messenger RNA-encoding collagen type I and transforming growth factor beta1 could be shown. An active inflammatory process could be shown until the end of the observation period, i.e., 2 months. CONCLUSIONS: The findings suggest that dibutyltin dichloride-induced pancreatitis in rats is suitable to study cellular interactions and mediators involved in the development of pancreatic fibrosis.
Animals↗
Tissue homogenization as a key step in extracting RNA from human and rat pancreatic tissue.
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Animals↗
[Interventional endoscopic therapy of chronic pancreatitis].
BACKGROUND AND AIM: Complications in chronic pancreatitis, such as duct occlusion due to stenosis or stones can be treated by interventional endoscopic procedures. The benefit of such procedures and the effect on the clinical course is still under debate. Therefore, it was the aim of this study to analyze the effect of endoscopic interventional procedures in more detail with respect to technical and clinical benefit. PATIENTS AND METHODS: 100 patients with chronic pancreatitis (cP) were studied retrospectively. In 58 patients an indication for interventional endoscopic therapy was given (45 +/- 12 yrs; 46 M, 12 F; cP 1 degree: n = 1, cP II degree: n = 8, cP III degree: n = 49). The patients were allocated to three groups: stenosis (n = 18), pancreatic duct stones (n = 18) and stenosis and pancreatic duct stones (n = 20). In two patients no visualization of the main pancreatic duct was performed due to cholestasis that was treated primarily. In total, 295 endoscopic procedures were performed (EPT, duct dilatation, plastic endoprothesis, ESWL, mechanical lithotripsy). Technical success was 95%. All stenoses could be dilated or bridged by plastic stents. Fragmentation of main pancreatic duct stones was achieved in 92%. The overall complication rate of all 319 endoscopies (fever, bleeding, stent dislocation) was 15.8%. Five patients had to undergo surgery, however, not as a direct consequence of complications from or unability of endoscopic procedures. 86% of the patients reported complete pain relief after the endoscopic-interventional procedures and 62% during the follow-up interval (7.4 +/- 6.3 months). 59% of the patients with weight loss and 58% of the patients with initially stable weight experienced a weight gain following endoscopic-interventional therapy. Individual patients showed improvement of endocrine or exocrine pancreatic function. 82% of the patients did not require inhouse treatment or emergency admission to the hospital whereas three admissions on average were recorded prior to endoscopic interventional treatment. Therefore, we conclude that a subset of patients does benefit from endoscopic interventional therapy of complications of chronic pancreatitis. However, a controlled prospective study is still mandatory.
Adolescent↗
Pancreatitis in systemic scleroderma.
We report the case of a 61-year-old woman, who suffered from abdominal pain, nausea, vomiting and fever. She had a past medical history of acute rheumatism, pyelonephritis and systemic scleroderma. Since 1971 she was hospitalized many times because of recurrent abdominal pain with increased serum amylase and lipase values. On admission, she was in distress and demonstrated clinical signs of acute pancreatitis. The link between systemic lupus erythematosus and acute pancreatitis is discussed in view of the reported cases of the world literature.
Acute Disease↗
Expression and function of receptors for extracellular matrix proteins in human ductal adenocarcinomas of the pancreas.
Extracellular matrix proteins (ECM) may influence cellular differentiation via their receptors, the integrins. We recently presented evidence that ductal adenocarcinomas of the pancreas are able to produce ECM in vitro and in vivo (Br J Cancer 1994;49:144-51). This study examines whether pancreatic carcinoma cells are able to interact with ECM by expressing functionally active integrins. In eight human pancreatic tumor cell lines (AsPC-1, BxPC-3, CAPAN-1 and -2, PANC, PaTu-2, -3, and -44) and six xenografted tumors RNA and protein expression of integrin subunits alpha 5 (fibronectin receptor), alpha 6 (laminin receptor), and alpha V (vitronectin receptor) was investigated. In addition, alpha 1-alpha 6 and alpha V as well as beta 1-beta 4 were studied by fluorescence-activated cell sorter analysis. Integrin function was tested by attachment assays. alpha 2, alpha 3, alpha 5, alpha 6, and alpha V as well as beta 1, beta 3, and beta 4 were expressed, at both the RNA and the protein level, by all pancreatic tumors in vitro and in vivo. The tumor cell lines showed dose dependent adhesion to collagen, fibronectin, and laminin. Integrin expression could be modulated in part by serum depletion. None of the tumors showed alpha 1, alpha 4, and beta 2. Tumor cell differentiation or production of ECM was not correlated with integrin expression. Pancreatic ductal adenocarcinomas express a certain pattern of functionally active integrins that enable interaction with most matrix proteins, e.g., collagen, fibronectin, and laminin. Pancreatic adenocarcinomas possess both the ligands and the receptors of the extracellular matrix network. We speculate that through both classes of molecules, the tumor cells may bind to fibroblasts and probably stimulate their growth. However, it remains unclear whether and how integrin-ECM interaction exerts an influence on tumor cell differentiation.
Animals↗
[Modern methods for detecting exocrine pancreas insufficiency in mucoviscidosis].
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Cystic Fibrosis↗
[Restriction enzyme mismatch polymerase chain reaction in the demonstration of Ki-ras-oncogene mutation in carcinoma of the pancreas].
A pilot study was undertaken to test whether combining the polymerase chain reaction with restriction fragment length polymorphism is suitable for the routine diagnosis of carcinoma of the pancreas. The method makes it possible to recognize point mutations in codon 12 of the Ki-ras oncogene. 60 cytological specimens from the pancreatobiliary tract, the bronchopulmonary system (by bronchoalveolar lavage or from pleural effusion) and ascites were tested. Results from nine pancreas carcinoma cell lines served as control. A PCR product was successfully amplified in all cell lines and 47 of the clinical specimens. In all eight samples in which a mutated Ki-ras oncogene was demonstrated, there was at least a suspicion of malignancy by cytological examination. A mutation was also found in four of five pancreas carcinomas. But no mutation was found in one, clinically certain, case of pancreas carcinoma. The described method is an elegant and, most of all, rapid means to complement and optimize any cytological diagnosis.
Ascitic Fluid↗
Actomyosin-based motility of endoplasmic reticulum and chloroplasts in Vallisneria mesophyll cells.
Intracellular localization and motile behaviour of the endoplasmic reticulum (ER), plastids and mitochondria were studied in living mesophyll cells of Vallisneria using the vital fluorochrome 3,3'-dihexyloxacarbocyanine iodide (DIOC6(3)). In quiescent cells, the ER was composed of a three-dimensional network of tubular and lamellar elements. Chloroplasts were distributed evenly throughout the cell periphery and appeared embedded within the ER network. The ER network was relatively stationary, with the exception of rare motile episodes occurring as movement of tubular ER strands and adjacent areas of the polygonal network in localized areas of the cell. During experimental induction of streaming, most of the lamellar ER elements transformed into tubules and together with the chloroplasts they began to translocate to the anticlinal walls to establish the circular streaming around the circumference of the cell. Microwave-accelerated fixation followed by immunofluorescence revealed an hitherto unknown phase of actin reorganization occurring within the cells and most interestingly at the surface of the chloroplasts during streaming induction. Myosin was localized in an ER-like pattern in quiescent as well as in streaming cells, with bright fluorescent label localized on mitochondria and proplastids. In addition, myosin label appeared on the surface of the chloroplasts, preferentially in streaming mesophyll cells. Motile activities were impeded by the actin-depolymerizing drug cytochalasin D (CD), the thioreagent N-ethylmaleimide (NEM), and thapsigargin, an inhibitor of the ER-Ca(2+)-ATPase. These inhibitors also interfered with the integrity of actin filaments, the intracellular distribution of myosin and calcium-homeostasis, respectively. These effects suggested an obligate association of at least one type of myosin with the membranes of ER and smaller organelles and are consistent with the appearance of another type of myosin on the chloroplast surface upon streaming induction.
Actins↗
[Relationship between secretory IgA in pancreatic secretions, in pancreatic tissue, and in the serum of patients with chronic pancreatitis].
In five patients with chronic pancreatitis we found secretory IgA (sIgA) in the pancreatic juice. In four control persons this was seen only in one case. In pancreatic tissue of three patients with chronic pancreatitis we detected both, IgA and secretory component by immunohistology. We suggest that sIgA in the pancreatic juice was partly produced in the pancreas.
Chronic Disease↗
Distribution of alpha B-crystallin in the anterior segment of primate and bovine eyes.
The presence and distribution of alpha B-crystallin in the anterior segment of human, monkey and bovine eyes was investigated immunocytochemically. In all three species the most intense staining was seen in the lens and in the nonpigmented and pigmented epithelial cells covering the tips of the pars plicata of the ciliary body. The staining intensity of the ciliary epithelial cells was comparable to that seen in the lens fibers. Strong labeling was also found in the corneal endothelium. In bovine eyes the presence of alpha B-crystallin in lens, ciliary epithelium of the pars plicata and corneal endothelium was also shown by biochemical analysis using SDS-PAGE and immunoblotting.
Aged↗
[Excretory pancreas function. Secretion of protein, calcium and citrate in probands with a normal pancreas and in patients with chronic pancreatitis].
Recent studies described an increased concentration of protein and calcium in association with a decreased concentration of citrate in pancreatic juice of patients suffering from chronic pancreatitis. These secretory changes may be of importance in the pathogenesis of chronic pancreatitis. The present study investigates pancreatic juices of 18 patients without pancreatic disease and 12 patients in an early phase of chronic pancreatitis in order to detect changes of the exocrine function of the pancreas in an early stage of the disease. In all persons the pancreatic juice was collected by endoscopic cannulation of the main pancreatic duct after i.v. stimulation with secretin and pancreozymin. The outputs and concentrations of protein, calcium and citrate were estimated. All of these parameters did not differ in control subjects and patients with chronic pancreatitis by univariate statistical analysis. However, a multivariate analysis detects differences in the biochemical composition of the secretions of controls and patients with chronic pancreatitis (efficiency of discrimination = 100%). Both in controls and in patients with chronic pancreatitis two calcium fractions were found after secretin stimulation: one secretory protein-associated fraction of 94 nmol calcium/mg protein and a protein-independent calcium fraction of 0.248 mmol/l, which diffuses paracellularly from the interstitium into the pancreatic juice. The results show that the secretory function of the exocrine pancreas is already disturbed in an early phase of chronic pancreatitis, whereas an increased lithogenity of the pancreatic juice cannot be detected.
Adult↗
[Pancreatic penetration of antibiotics].
Antibiotic therapy is indicated in acute pancreatitis because the most common complication and the mean reason for mortality is a bacterial infection. Concentrations of nine antibiotics from various classes were studied in the pancreatic tissue and pancreatic juice of patients and dogs. The volume of distribution is the most valuable parameter for predicting the potential pancreatic penetration of a substance. As a result of our pharmacokinetic studies mezlocillin and cefotiam, especially ciprofloxacin, have the most antiinfectious potential in treatment of acute pancreatitis. Metronidazole is suitable for combination in cases of pancreatic infections covering anaerobic bacteria.
Animals↗
[Exocrine function of a heterotopically transplanted pancreas segment in humans].
Pancreatic secretion is involved in circadian regulation of the whole organism. This observation was obtained in animals and humans with pancreatic fistulas. We report on three patients in whom the pancreas was removed totally or subtotally because of chronic pancreatitis with severe pain. A segment of the removed gland was transplanted into the thigh in order to preserve endocrine function. The pancreatic duct was drained by a polyethylene tube until pancreatic duct occlusion. Postoperatively juice volume increased within 3 days and remained constant afterwards with 300 ml in 24 hours. Secretin, cholecystokinin and food intake are able to stimulate the transplanted segment in a typical manner. The secretion showed circadian changes. In all patients the pancreatic juice content of protein, amylase, trypsinogen, calcium, and zink decreased till 11 p.m. After 11 p.m. the content of all substances increased and reached maximal values at 6 a.m. Flow rates and therefore output per minute decreased greatly till 6 a.m. The large juice volume of 300 ml in 24 hours is perhaps the consequence of a break down of the feedback mechanism between intraduodenal trypsin activity and CCK-release. The changes during the night may be of pathogenetic relevance. In the early morning pancreatic juice is highly concentrated and the flow rate is very low. High protein concentrations, high calcium concentrations, and reduced flow rates may lead to protein and calcium carbonate precipitates. This mechanism is under discussion in the pathogenesis of chronic pancreatitis.
Adult↗
[Obstructive jaundice caused by Ascaris lumbricoides].
In middle Europe biliary complications caused by Ascaris lumbricoides are very rare. We report on endoscopic removal of an Ascaris out of the common bile duct in a 81-years-old woman.
Aged↗
[Groups at risk for colorectal tumors].
Genetic and environmental factors are involved in the development of colorectal cancer. The most important prognostic factor is the pathological stage at the time of diagnosis. Therefore it is called for early detection, screening for colorectal cancer, and definition of risk groups. High risk groups are familial polyposis coli, ulcerative colitis, cancer family syndrome, ureterosigmoidostomy, colorectal adenomas, and after resection of colorectal cancer. For these groups a lifelong follow-up and treatment is necessary. But groups with lower risk (Crohn's disease, breast cancer, endometrial cancer, colorectal cancer within the family, gastric polyps, and partial gastrectomy in benign ulcer) need attention too. Colonoscopy with biopsy is one of the most important techniques during follow-up of these patients.
Adenomatous Polyposis Coli↗
[Changes in pure human pancreatic juice in chronic pancreatitis].
Investigations of pancreatic juice revealed new insights into the pathogenesis of chronic pancreatitis (cP). But many results are contradictory. In this paper pure human pancreatic juice from patients with cP (n = 14) was compared with results obtained from normal subjects (n = 22). The pancreatic juice was obtained endoscopically recording the absorption (280 nm) simultaneously. By means of this special technique 4 fractions could be exactly distinguished: 1. wash-out-period, 2. phase of secretin action, 3. phase of pancreozymin (CCK) action, and 4. post-CCK-phase. Total protein, trypsinogen, zinc sodium, and potassium were determined. In fraction 1 (wash-out-period) mean values of protein, trypsinogen and zinc are lower in patients with cP compared with control subjects. In case of zinc the difference is statistically significant. In fraction 2 (secretin-phase) no differences could be detected between cP and control subjects. In contrast in fraction 3 (CCK-phase) mean values of protein and trypsinogen are lower in control subjects than in patients with cP. But the standard deviations are so high that all differences are not statistically significant. The results indicate that under fasting conditions the pancreatic juice content of protein, trypsinogen and zinc is lower in patients with cP. But patients with cP can be stimulated much better with CCK than control subjects. Till now such a different behaviour during wash-out-period and CCK-stimulation is not reported in the literature.
Cholangiopancreatography, Endoscopic Retrograde↗