Rotating hexagonal pattern in a dielectric barrier discharge system.

Here, we report on the experimental observation of a rotating hexagonal pattern in a continuous dissipative medium. The system under investigation is a planar dielectric barrier gas-discharge cell. The pattern consists of a set of current filaments occupying the whole discharge area and rotating as a rigid body. The symmetry of the rotating hexagons is lower than the symmetry of the stationary hexagonal pattern. We study the dynamics of the pattern, especially peculiarities of its rotational velocity. The temperature of the gas is found to be an important quantity influencing the rotating hexagons.

[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera]. / Unklare Leberfibrose bei einer 42-jährigen Patientin mit Polycythaemia vera.

A 42-year-old patient was admitted to hospital because of ascites and polyglobulia. Laboratory tests revealed reduced liver function and a significant elevation of all three hematopoietic cell lines. Liver fibrosis and polycythemia vera were diagnosed by histologic examination. The most frequent causes for liver fibrosis were serologically excluded. Ultrasound combined with Doppler imaging revealed an obstruction of the right hepatic vein, which was indicative of Budd-Chiari syndrome. BCS can occur under fulminant and nonfulminant conditions, which can result in progressive damage of the liver. Phlebotomy and combined therapy with low-dose aspirin and anagrelide achieved permanent reduction of the elevated blood parameters. In the follow-up the patient's clinical course was stable without hepatic decompensation.

Noise-covered drift bifurcation of dissipative solitons in a planar gas-discharge system.

The trajectories of propagating self-organized, well-localized solitary patterns (dissipative solitons) in the form of electrical current filaments are experimentally investigated in a planar quasi-two-dimensional dc gas-discharge system with high Ohmic semiconductor barrier. Earlier phenomenological models qualitatively describing the experimental observations in terms of a particle model predict a transition from stationary filaments to filaments traveling with constant finite speed due to an appropriate change of the system parameters. This prediction motivates a search for a drift bifurcation in the experimental system, but a direct comparison of experimentally recorded trajectories with theoretical predictions is impossible due to the strong influence of noise. To solve this problem, the filament dynamics is modeled using an appropriate Langevin equation, allowing for the application of a stochastic data analysis technique to separate deterministic and stochastic parts of the dynamics. Simulations carried out with the particle model demonstrate the efficiency of the method. Applying the technique to the experimentally recorded trajectories yields good agreement with the predictions of the model equations. Finally, the predicted drift bifurcation is found using the semiconductor resistivity as control parameter. In the resulting bifurcation diagram, the square of the equilibrium velocity scales linearly with the control parameter.

Relevance of variants in serum antiproteinases for the course of chronic pancreatitis.

BACKGROUND: Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP). The aim of this study was to determine the role of genetic variants of the main serum antiproteinases alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (A2M) for the course of chronic pancreatitis. METHODS: 124 patients with non-alcoholic chronic pancreatitis (with PRSS1 or SPINK1 mutations or idiopathic pancreatitis) and 64 healthy controls were investigated for the AAT mutations PiS and PiZ, and the PiM determining variants R101H, V213A, E376D. In 101 subjects, the 'bait region' of A2M was sequenced. A pentanucleotide deletion in the bait region of A2M was analysed in 147 chronic pancreatitis (CP) patients and 87 controls. RESULTS: The lowest prevalences of V213A and E376D were found in PRSS1 patients, whereas an increased rate of these mutations was present in the SPINK1 group, and the highest prevalence was found in patients with idiopathic pancreatitis. The prevalence of PiM variants was higher in patients with early onset CP than in late onset (P < 0.05 for E376D). The coding region of the bait region of A2M was of wild type in all investigated subjects. The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls. CONCLUSIONS: Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis.

[Laryngo-hypopharyngo-esophagectomy in advanced hypopharyngeal carcinoma. Is radical surgery intervention still justified today?]. / Laryngo-Hypopharyngo-Osophagektomie beim fortgeschrittenen Hypopharynxkarzinom. Ist dieser radikalchirurgische Eingriff heute noch gerechtfertigt?

Minimal invasive laser surgery with preservation of the organs is well established in the treatment of hypopharynx carcinoma. In cases of advanced tumors of the hypopharynx, which can not be managed by laser surgery, the combined radio-chemo therapy becomes the treatment of choice because of the low morbidity and the comparable results. The indication for an operative procedure, which means loss of larynx and oesophagus, is seen more and more restrictively. From 1993 to 1997 101 patients with advanced neoplasm of the hypopharynx or larynx (larynxcarcinoma T4; hypopharynx carcinoma T3-T4 with N > 2b) were treated in the Department of Otolaryngology of the University of Regensburg. 5 of these patients underwent a laryngohypopharyngoesophagectomy. Only patients with a severe dysfunction of the larynx (dyspnea, dysphagia, aspiration) were selected for this procedure. Postoperative complications were: one insufficiency of anastomosis with secondary bleeding and five pleura effusions. In all cases postoperative radiation began within six weeks after the operation. All patients were nourished orally when they were discharged from hospital. The mean follow up was 21 months. During this time none of the patients died. In one case pulmonary metastasis was found after 11 months. In another case a regional recurrence was diagnosed after 11 months and was removed by operation. No local recurrence was found at that time. This operative procedure can be done only in experienced and well trained medical centers. Furthermore excellent cooperation of the operating teams and strong regard to the selection criteria is obligatory.

Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation.

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha contributes to the development of acute pancreatitis. Because TNF-alpha is involved in the control of apoptosis, we studied its interaction with the pancreatic apoptotic pathway. METHODS: Pancreatic acinar AR4-2J cells were used. Apoptosis was monitored by morphologic and biochemical criteria. RESULTS: TNF-alpha induced apoptosis in AR4-2J cells. Induction was strongly enhanced in cells treated with actinomycin D, suggesting that TNF-alpha activated concomitantly an antiapoptotic mechanism through newly synthesized proteins. This mechanism involved activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases because their inhibition worsened TNF-alpha-induced apoptosis. The antiapoptotic pancreatitis-associated protein (PAP) I is a candidate for mediating TNF-alpha activity. Its expression is induced by TNF-alpha, and cells overexpressing PAP I show significantly less apoptosis on exposure to TNF-alpha. We examined whether TNF-alpha induction of PAP I expression was mediated by NF-kappaB or MAP kinases by using specific inhibitors of both pathways. Inhibition of NF-kappaB had no effect. However, inhibitors of MEK1 eliminated PAP I induction. CONCLUSIONS: TNF-alpha induces concomitantly proapoptotic and antiapoptotic mechanisms in pancreatic AR4-2J cells. Antiapoptotic mechanisms are mediated by NF-kappaB and MAP kinases, and PAP I is one of the effectors of apoptosis inhibition.

[Significance of inter-sphincter rectal resection with colo-anal anastomosis in deep seated rectal carcinoma]. / Die Bedeutung der intersphinkteren Rektumresektion mit koloanaler Anastomose beim tiefsitzenden Rektumkarzinom.

From October 1992 to December 1996, 204 patients with rectal cancer were treated with tumor resection. Of all carcinomas 94 were localised in the distal, 71 in the middle and 39 in the proximal third of the rectum. Curative resection could be achieved in 74% to 85% of the cases depending on tumor localisation. A local R0-resection (no residual tumor) was achieved in 92% to 100%, partly due to preoperative radiochemotherapy in cases of locally advanced cancer. The percentage of protective stoma application ranged from 25% of the total number of resections to 89% in those cases with intersphincteric rectal resection. The peri- and postoperative complications were thoroughly documented. The number of complications increased with the distal extent of rectal resection. The median follow up period was 24.5 months. Local tumor recurrence was observed in 6 cases (3.1%) independent of the tumor location. Distant metastasis was seen in 16% of all patients during the follow up period. 73% of all patients are still alive, 23% died of tumor related and 4% of non tumor related reasons. Complete postoperative stool continence was reported by 73% of all patients, 14% were incontinent for liquid stool and 13% were affected by total stool incontinence. Excluding those who underwent rectum extirpation, 39% of the patients had a stoma. The extent of stool continence was closely related to the operative procedure. With intersphincteric resection, complete stool continence could only be achieved in 40% of the patients whereas 18% were incontinent for liquid stool, 14% were completely incontinent and 29% had a stoma at the time of observation. The rate of local recurrence was not increased after intersphincteric resection.

Cloning and expression of the human p8, a nuclear protein with mitogenic activity.

We have previously identified a new rat mRNA, provisionally named p8, which showed a strong, but transient, induction in the pancreas in response to acute pancreatitis. We report here the cloning and sequencing of the human p8 cDNA. The human p8 polypeptide is 82 amino acids long and shows an overall identity of 74% with the rat counterpart. The complete structure of the p8 gene was also established. The p8 gene comprises three exons separated by two introns and the gene was mapped to chromosome 16. Analysis of the p8 primary structure suggested the presence of a bipartite motif of nuclear targeting, indicating that p8 may function within the nucleus. This presumption has been confirmed by transfection of COS-7 cells with the p8 cDNA followed by immunostaining with specific antibodies. p8 mRNA expression is induced in some, but not all, cells by serum starvation and ceramide. To analyze the p8 function, we stably transfected HeLa cells with a p8 expression plasmid, and measured their growth and their sensitivity to apoptosis. Response to TNF alpha and staurosporine-induced apoptosis was not modified by p8 expression. However, cells expressing p8 grew significantly more rapidly.

PAP I interacts with itself, PAP II, PAP III, and lithostathine/regIalpha.

PAP I, PAP II, PAP III, and lithostathine/regIalpha are members of a multigenic family of proteins expressed in several tissues. PAP I was shown to be antiapoptotic, mitogenic, and anti-inflammatory and can promote cell adhesion to the extracellular matrix. Lithostathine/regIalpha can be mitogenic. Because polymerization might regulate activity, we examined the ability of rat PAP I to interact with itself (homodimerization), PAP II, PAP III, and lithostathine/regIalpha (heterodimerization) by the yeast two-hybrid system, affinity experiments, and crosslinking. PAP I interacted significantly with all members of the PAP protein family, homodimerization showing the strongest interaction as judged by the beta-galactosidase test. This was confirmed by showing specific affinity between a MBP-rPAP I fusion protein and the native rPAP I. Finally, crosslinking experiments showed that rPAP I formed dimers in solution. These findings should be taken into account in functional studies involving PAP I and PAP-related proteins.

PAP gene transcription induced by cycloheximide in AR4-2J cells involves ADP-ribosylation.

We report in this paper that cycloheximide induces PAP mRNA expression in the pancreatic acinar cell line AR4-2J in a dose- and time-dependent manner. We analyzed whether stabilization of the PAP mRNA or the direct induction of its transcription contributed to the induction of PAP mRNA expression by the drug. We first infected the cells, which do not express PAP mRNA constitutively, with a recombinant adenovirus in which the PAP cDNA was subcloned downstream of the CMV promotor, to obtain high levels of transcript. Then, transcription was pharmacologically blocked, the cells were treated with cycloheximide, and the PAP mRNA concentration was monitored over 8 h by Northern blot. PAP mRNA concentration remained unchanged for 4 h and then decreased in both cycloheximide-treated and control cells, ruling out a significant contribution of posttranscriptional regulation in cycloheximide induction. Direct regulation of gene transcription is therefore likely and we investigated whether it could involve ADP-ribosylation. Cycloheximide-induced cells were treated with two chemical inhibitors of poly(ADP-ribose) polymerase. 3-Aminobenzamide inhibited 75% of PAP gene induction and 4-hydroxyquinazolone, the highly specific inhibitor of the enzyme, blocked almost completely PAP expression, suggesting that ADP-ribosylation was indeed required for the upregulation of PAP gene expression by cycloheximide.

Overexpression of the PC3/TIS21/BTG2 mRNA is part of the stress response induced by acute pancreatitis in rats.

We have previously shown that the acute phase reaction of the pancreas is a powerful emergency mechanism which protects the organism against further pancreatic aggression. In an attempt to understand the mechanisms involved in this protective effect we tried to characterize at the molecular level the phenotypic changes of the pancreatic cell during acute stress. Using a systematic approach, we identified the PC3/TIS21/BTG2 mRNA as strongly overexpressed in pancreas during the acute phase of pancreatitis. PC3/TIS21/BTG2 mRNA is also overexpressed in liver and kidney during acute pancreatitis but not in the other tissues analyzed. In addition, PC3/TIS21/BTG2 mRNA is overexpressed in kidney after a 30-min ischemia. Since acute pancreatitis and kidney ischemia-reperfusion-induced injury were associated with apoptosis, and PC3/TIS21/BTG2 has an antiapoptotic activity, we speculate that this protein may play a role in the control of apoptosis progression in these tissues.

Pancreatitis-associated protein is upregulated in mouse pancreas during acute pancreatitis.

Pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein strongly expressed during acute pancreatitis in the rat and human. We hypothesized that its expression was part of a general and coordinated response of the organ against aggression. An opposite pattern of PAP I mRNA expression has recently been described in the mouse. The murine PAP I mRNA was described to be highly expressed in normal pancreas and down-regulated during pancreatitis. The important implications of these unexpected findings led us to investigate the expression of murine PAP I in cerulein-induced pancreatitis. Northern blot analysis demonstrated a very low level of PAP I mRNA in the healthy mouse pancreas and strong overexpression during acute pancreatitis. Western blot analysis confirmed that changes in pancreatic PAP I levels were parallel to those of the mRNA and the protein was localized by immunohistochemistry to the acinar cells. It was concluded that, during the course of acute pancreatitis, the pattern of PAP I expression in the mouse pancreas was comparable to that already observed in the rat and human. Although we have no explanation for the discrepancy between our results and those recently reported, the expression pattern of PAP I in the mouse exocrine pancreas described in the present study suggests that the pancreatic response to aggression might be conserved in mammals.

The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis.

BACKGROUND & AIMS: Free radicals are involved in the pathogenesis of acute pancreatitis, during which pancreatitis-associated protein (PAP)-I is overexpressed. We explored whether PAP-I expression could be induced by oxidative stress and whether it could affect apoptosis. METHODS: AR4-2J cells were exposed to H2O2 or menadione, and PAP-I messenger RNA (mRNA) expression was analyzed by Northern blotting. RESULTS: Maximal expression was observed with 0.1 mmol/L H2O2 or with 0.05 mmol/L menadione. Induction was detectable after 12 hours, reached a climax at 18 hours, and then decreased. Pretreatment of the cells with pyrrolidine dithiocarbamate completely abolished PAP-I mRNA induction, suggesting involvement of NFkappaB in the signaling pathway. These findings were confirmed in transient transfection assays using a plasmid containing the PAP-I promoter linked to the chloramphenicol acetyltransferase reporter gene. Then the relationship between PAP-I induction and protection against cell damage during oxidative stress was considered. Constitutive PAP-I expression in AR4-2J cells after transfection with PAP-I complementary DNA conferred significant resistance to apoptosis induced by low doses of H2O2 but not to necrosis induced by high doses of H2O2. CONCLUSIONS: These results suggest that during oxidative stress, PAP-I might be part of a mechanism of pancreatic cell protection against apoptosis.

[Distal stenosis of the choledochus in chronic pancreatitis: endoscopic drainage or operation?]. / Die distale Choledochusstenose bei der chronischen Pankreatitis: Endoskopische Drainage oder Operation?

With the less invasive techniques for complications regarding chronic pancreatitis, such as tubular choledochostenosis, the endoscopic transpapillary bile drainage therapy by means of endoprosthesis has undergone an enlargement of its indications range. Blocked and dislocated prostheses, however, further raise the already existing possibility of septic complications. With 15 out of 43 patients undergoing medium-term endodrainage treatment, we observed different resulting conditions of chronic cholestasis, such as abscess-forming cholangitis, hepatic abscesses, retroperitoneal phlegmon and sepsis up to biliary cirrhosis. Thus, in the case of chronic pancreatitis we still regard choledochostenosis- which, due to scarring, is mostly fixed-as a primary indication for operation.

[Asymptomatic choledochal cyst]. / Asymptomatische grosse Choledochuszyste im Erwachsenenalter.

HISTORY AND FINDINGS: A 45-year-old woman sustained an ankle fracture in an accident. At examination she was found to have marked pallor of skin and mucosae. There was no hint for melaena or haematemesis. INVESTIGATIONS: Biochemical tests showed marked iron deficiency anaemia (haemoglobin 7.5 g/dl) and raised serum bilirubin and C-reactive protein levels (1.94 mg/dl and 85.2 mg/l, respectively). Abdominal sonography revealed a cystic space-occupying mass (8 x 4.5 cm) projecting onto the gallbladder, interpreted as a choledochal cyst of unknown origins without bleeding. After treatment of the ankle fracture an endoscopic retrograde cholangiopancreatography was performed. This showed a large cyst of the choledochal duct into which the cystic and choledochal ducts entered, without evidence of tumour or haematoma. There was also a 1 cm prepapillary common choledochal and Wirsung duct. TREATMENT AND COURSE: With these findings, the diagnosis of a congenital choledochal cyst (type Ia of Todani) could be made. After healing of the ankle fracture the cyst was removed and a Roux Y-anastomosis created. The cystic tissue was benign. At follow-up 6 months later the patient was symptom-free and no longer anaemic. CONCLUSIONS: Congenital choledochal cysts are very rare in Europeans. The symptom-free course with anaemia and no manifestation until adulthood is also very unusual.

[Repeat liver resection in colorectal liver metastases]. / Wiederholte Leberresketion bei kolorektalen Lebermetastasen.

For patients with recurrent operable liver metastases from colorectal cancer operative resection is the only chance of getting rid of their tumorous disease for a longer time. As there are not therapeutic alternatives more and more authors are reporting on repeated resections of liver metastases. From 1986 to 1994 we performed 12 recurrent liver resections with curative intent in 8 patients suffering from liver metastases of colorectal cancer: 4 synchronous and 4 metachronous metastases were removed, the primary procedure being anatomic hemihepatectomy in 5 cases and segmentectomy or bisegmentectomy in 3 cases. The mean time interval between the first and the second resections was 14 (4-23) months. Two patients underwent 4 consecutive liver resections because of recurrent metastases. In these cases the interval between the second, third and fourth procedures was 10 months. The postoperative complication rate was 16% and not a single patient died in hospital. Three patients died an average of 28 (9-54) months after the last liver resection, and the other 5 patients are still alive after an average of 14 (4-28) months: 3 are free of tumor and 2 have recurrent metastases in the liver. Compared with untreated or only locally treated cases, patients in whom operative risk is low can achieve prolonged survival times after resections of colorectal metastases to the liver.

[Changes in therapy of severe acute pancreatitis]. / Wandel in der Therapie der schweren akuten Pankreatitis.

Report about the treatment of necrotizing pancreatitis in the years 1988 until 1991. A rigorous conservative therapy was preferred, so that only 8.6% of the 140 patients underwent surgery. In 11 cases a continuous venous-venous hemofiltration (CVVH) was applied to patients with most serious clinical course and multi-system failure. The overall lethality rate of all treated patients was 7.9%. The present results show, that, eliminating mediators by hemofiltration, system failure in connection with sterile necrosis can be treated with a good success rate. Therefore toxic organ failure should no longer be regarded as an imperative indication for operation. We recommend strict intensive care including CVVH and antibiotical prophylaxis for treatment of sterile necrosis, while surgical therapy should only be applied to patients with bacterial contamination of pancreatic necrosis.

Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.