Protein Plugs Research Articles

Su1239 A Prospective Trial of Secretin Infusion for Refractory Type B Pain in Chronic Pancreatitis

Background & Aims: Chronic pancreatitis (CP) is characterized by chronic inflammation and progressive pancreatic fibrosis leading eventually to the loss of exocrine and endocrine pancreas functions. The loss-of-function mutations of serine protease inhibitor Kazal type 1 (SPINK1) gene are associated with various forms of human CP. We previously showed that deletion of Spink3, the mouse homologue of SPINK1, causes pancreatitis-like changes in the mouse. Spink3-/mice die within 2 weeks after birth, making it impossible to monitor long-term effects of Spink3 deficiency. The aim of this study was to rescue the Spink3-/phenotype by generating Spink3-/mice with knocked-in SPINK1, and to characterize timedependent changes in the pancreas in this geneticmodel. Methods:We placedCAG promoterSPINK1 minigene (CAG-SP1) into diaphanous homolog 2 (Diap2) locus, which is located on X chromosome, using the Cre-Lox technology. X-inactivation is a process whereby one of the two copies of the X chromosome present in female mammals is inactivated. By utilizing X-inactivation, we were able to create mice in which SPINK level was partially, but not completely, reduced compared with the wild type. The CAG-SP1 knock-in mice were crossed to Spink3+/mice, thus generating Spink3-/-; CAG-SP1 knock-in mice. Mice were followed up for up to 6 months. Time-dependent changes in pancreatic histology, autophagy, inflammatory infiltration, acinar cell death, stellate cell activation, fibrosis, as well as trypsinogen activation and serum amylase were measured. Results: Spink3-/-;YXCAG-SP1, as well as Spink3-/-;XCAG-SP1/CAG-SP1 mice in which CAG-SP1 was present on both X chromosomes, showed no abnormalities in pancreas or any other organ during the 6 months of observation, indicating that human Spink1 rescues Spink3 deficiency in mice. Spink3-/-; XCAG-SP1/wild mice in which CAG-SP1 is present on only one of the two X chromosomes, showed slight growth retardation but were healthy and fertile. Pancreas of Spink3-/-; XCAGSP1/wildmice at birth contained both normal and degenerated acinar cells, with accumulation of autophagic vacuoles. The Spink3-/-;XCAG-SP1/wild mice time-dependently developed pathologic features of CP, including loss of acinar cells, intralobular fibrosis with activated stellate cells, and neutrophilic infiltration. In the interlobular areas, fibrosis was not evident, but instead prominent lipomatosis was observed. Interlobular ducts were dilated and contained protein plugs, which resembled CP in human. Older mice displayed acinar-ductal metaplasia and prominent expression of proto-oncogenes Egfr, Her2, and Ras, but did not develop pancreatic intraepithelial neoplasia. Conclusions: The results re-inforce the role of SPINK1/Spink3 deficiency in the development of CP and indicate that CP conditions trigger factors promoting pancreatic cancer development.

Physiology and pathophysiology of bicarbonate secretion by pancreatic duct epithelium.

HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl- -rich fluid. Ductal HCO3- secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3- concentration of the juice under secretin stimulation reaches 140-150 mM. Thus pancreatic duct cells secrete HCO3- against a approximately 7-fold concentration gradient. HCO3- secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3 secretion across the apical membrane is largely mediated by SLC26A6 CI- -HCO3- exchanger. In distal ducts where the luminal HCO3- concentration is already high, most of the HCO3- secretion is mediated by HCO3- conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral-acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.

Molecular Mechanisms of Pancreatic Stone Formation in Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s) is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in secretion. In previous studies, we have found that CFTR is largely mislocalized to the cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids normalizes the localization of CFTR to the proper apical membrane at least in autoimmune pancreatitis. From these observations, we could conclude that the mislocalization of CFTR is a cause of protein plug formation in CP, subsequently resulting in pancreatic stone formation. Considering our observation that the mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very likely that these pathological conditions can also be treated by corticosteroids, thereby preventing pancreatic stone formation in these patients. Further studies are definitely required to clarify these fundamental issues.

Congenital biliary dilatation may consist of 2 disease entities

Background/Purpose This study aims to establish the possible mechanisms of pathogenesis of congenital biliary dilatation and to classify the disease accordingly. Methods Radiologic features of congenital biliary dilatation and pancreaticobiliary malunion in 107 affected children were examined and correlated with laboratory results. Relative lengths/diameters were calculated to provide comparison between children of different ages. Intraluminal pressures of common bile duct (CBD) were measured intraoperatively. Results The minimal relative diameters of distal CBD negatively correlated with the maximal relative diameters/lengths of dilated CBD, the maximal relative diameters of common hepatic duct, and left/right hepatic ducts. The intraluminal pressure in patients with a stenotic distal CBD (stenotic group) was significantly higher than that in patients with a nonstenotic distal CBD (nonstenotic group). The narrower the distal CBD, the more deranged the liver function. Conversely, serum/bile amylase levels were more elevated in the nonstenotic group. Common channel protein plugs were only found in the nonstenotic group, whereas common hepatic duct strictures, intrahepatic duct dilatations, and calculi were detected more frequently in the stenotic group. Conclusion We propose to categorize congenital biliary dilatation into 2 subgroups: (1) cystic type with stenotic distal CBD associated with deranged liver function and common hepatic duct stricture and (2) fusiform type with nonstenotic distal CBD associated with pancreatitis and common channel protein plugs. Different underlying pathologies of each group require different operative strategies.

Intralaparoscopic endoscopy: its value during laparoscopic repair of choledochal cyst

We report our experience of laparoscopic repair of choledochal cyst (CC). We reviewed 10 CC patients (mean age 3.3 years) who had lap CC repair. Eight patients had minimally dilated/fusiform type CC (fusiform CC) and presented with pancreatitis, and two had cystic type CC (cystic CC). Using conventional trocar placement (right upper quadrant, left paraumbilical, left upper quadrant; laparoscope in the umbilicus), the CC was isolated and transected at mid level. An additional 3.9 mm trocar in the left epigastrium was used to introduce a fine ureteroscope. Its tip was inserted into the common channel through the distal CC to remove protein plugs (PP) under laparoscopic guidance. To perform intralaparoscopic endoscopy of the intrahepatic ducts, a trocar placed in the left lower quadrant was used. Two extra trocars (3 and 5 mm) were added for hepatico-jejunostomy anastomosis (HJA); one lateral right subcostal, and one between the right subcostal and right upper quadrant trocars, respectively. HJA was performed using interrupted 5/0 absorbable sutures with the right upper quadrant trocar as a needle holder in the right hand, 5 mm for the laparoscope, and 3 mm subcostal trocar as a needle receiver in the left hand. Both the right and left edge sutures were exteriorized and used as traction sutures during anastomosis of the anterior wall. Seven of eight fusiform CC patients had PP (massive in 3, moderate in 3, little in 1) in the common channel successfully removed with normal saline washouts through the side channel of the ureteroscope. Eight of ten CC patients had debris (moderate in 4, little in 4) in the intrahepatic ducts. Two complications were encountered; pancreatitis that resolved with conservative management and duodenal obstruction due to inadequate Roux-en-Y limb fixation that was treated by laparoscopic intervention. All are well after a mean follow-up of 12 months with cosmetically attractive wounds. Although three additional trocars are required, we recommend our HJA technique and intraoperative common channel endoscopy during laparoscopic repair of CC.

The Anti-Inflammatory Cytokine Interleukin 19 Is Expressed By and Angiogenic for Human Endothelial Cells

To characterize the expression and function of interleukin (IL) 19, a recently described T-helper 2 anti-inflammatory IL, on endothelial cell (EC) pathophysiological features. The expression and effects of anti-inflammatory ILs on EC activation and development of angiogenesis are uncharacterized. We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal, human coronary endothelium and can be induced in cultured human ECs by serum and basic fibroblast growth factor. IL-19 is mitogenic and chemotactic, and it promotes EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cordlike structure formation of cultured ECs and enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in gelatinous protein (Matrigel) plugs in vivo. To our knowledge, these data are the first to report expression of the anti-inflammatory agent, IL-19, in ECs; and the first to indicate that IL-19 is mitogenic and chemotactic for ECs and can induce the angiogenic potential of ECs.

Laparoscopic-assisted clearance of protein plugs in the common channel in children with choledochal cysts

BackgroundThe purpose of the study was to assess the efficacy of laparoscopic-assisted removal of protein plugs from the common channel in choledochal cysts. MethodsBetween 2001 and 2009, 34 patients with choledochal cysts (mean age, 4.98 years) with protein plugs in the common channel successfully underwent laparoscopic cyst excision and Roux-en-Y hepatojejunostomy. Under direct vision during laparoscopy, urethroscopes or catheters were inserted into the common channel to irrigate and remove the protein plugs. Complete clearance was confirmed by either direct urethroscopic visualization or cholangiogram that demonstrated (1) no filling defects in the common channel, (2) significant reduction of common channel diameter, (3) free passage of contrast agent into the duodenum, and (4) no pancreatic duct reflux. Operative time and blood loss, postoperative hospital stay, duration of drainage, postoperative complications, perioperative ultrasonographic findings, and laboratory results were reviewed. ResultsProtein plugs were completely removed in all the patients. The mean operative time, postoperative hospital stay, and drainage duration were 3.51 hours, 7.08 days, and 3.41 days, respectively. The median follow-up period was 32 months. Neither mortality nor complications of pancreatic juice leak, pancreatitis, or stone formation were observed. Liver function parameters and serum amylase levels returned to normal postoperatively. ConclusionsLaparoscopic-assisted clearance of the protein plugs in the common channel in choledochal cyst is effective, with good medium-term results observed.

Relapsing acute pancreatitis caused by protein plugs in a remnant choledochal cyst

Relapsing acute pancreatitis caused by protein plugs in a remnant choledochal cyst

Role of multislice computed tomography in the diagnosis of gene-mutation-associated pancreatitis (GMAP)

The aim of this study was to review the computed tomography (CT) features of the pancreatic parenchyma and ducts in patients with gene-mutation-associated pancreatitis (GMAP). Twenty-five patients with GMAP were included in this retrospective study. Patients were divided into two groups according to the time interval between the onset of symptoms and the first CT examination (group A ≤24 months and group B >25 months). On qualitative image assessment, in group A patients, pancreatic duct stones were detected in 2/13 with GMAP. All stones were calcified and homogenous. Enhancement of the pancreatic parenchyma was hypovascular in 7/13 patients. In group B patients, pancreatic duct stones were detected in 12/12 with GMAP. Stones were calcified in 10/12 cases and noncalcified (protein plugs) in 2/12; in 5/10 cases, the calcified stones were heterogeneous with noncalcified central core (bull's-eye appearance). Enhancement of the pancreatic parenchyma was hypovascular in 12/12 patients. On quantitative image assessment, in group A patients, the mean diameter of duct stones was 0.6 mm (range 0-5 mm). Mean diameter of the main duct in the pancreatic head and body/tail was 4.8 mm and 4.9 mm, respectively. In group B patients, the mean diameter of duct stones was 21.9 mm (range 2-50 mm). Mean diameter of the main duct in the pancreatic head and body/tail was 18.8 mm and 13.9 mm, respectively. CONCLUSIONS|: In patients with GMAP and time interval between symptom onset and first CT scan ≤24 months (group A), CT identified normal or slightly increased parenchymal thickness and a main pancreatic duct of normal calibre and without duct stones. In contrast, in patients with GMAP and time interval between symptom onset and first CT scan >25 months (group B), it identified large-calibre duct stones with bull's-eye appearance.

Intraoperative endoscopy during choledochal cyst excision: extended long-term follow-up compared with recent cases

Introduction We routinely perform intraoperative endoscopy (IOE) of the intrahepatic bile duct (IHBD) and intrapancreatic bile duct (IPBD) with a pediatric cystoscope during excision of choledochal cyst (CC). Here we compare extended long-term follow-up patients with a series of recent cases. Methods We compared 25 CC patients treated over the past 5 years (group 1) with 69 CC patients treated between 1986 and 1998 and followed up for more than 10 years (group 2), focusing on stone formation. Results In group 1 (mean follow-up, 2.6 years) IOE identified IHBD debris in 7 (28%) of 25 and IPBD protein plugs in 9 (36%) of 25. In group 2 (mean follow-up, 14.6 years) IOE identified IHBD debris in 11 (16%) of 69 and IPBD protein plugs in 17 (25%) of 69. There was no relation between type of CC and incidence of IHBD debris or IPBD protein plugs. The incidence of postoperative stones to date is 0% in group 1 and 2.9% in group 2, rates far lower than those reported in the literature. Conclusions We attribute our lower incidence of stones directly to IOE and recommend that it be performed routinely during cyst excision. It is simple, is effective, and improves outcome.

Lactoferrin in Gastrointestinal Disease

Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The presence of lactoferrin in body fluids is proportional to the flux of neutrophils and its assessment can provide a reliable biomarker for inflammation. In gastrointestinal diseases increased fecal lactoferrin is a sensitive and specific surrogate marker for inflammatory bowel diseases in patients with chronic diarrhea and pain, and ascites lactoferrin can also provide a promising and reliable biomarker for bacterial peritonitis. Lactoferrin in pancreatic juice and stone could provide pathophysiological information of protein plug and stone formation in the pancreatic duct. Serum anti-lactoferrin autoantibody might contribute to the clarification of the pathogenetic mechanisms of autoimmune pancreatitis and liver diseases, although its diagnostic and prognostic value appears to be limited. Further studies will be necessary to elucidate the exact details.

Acidic and Basic Solutions Dissolve Protein Plugs Made of Lithostathine Complicating Choledochal Cyst/Pancreaticobiliary Maljunction

Symptoms of choledochal cysts are caused by protein plugs made of lithostathine, which block the long common channel and increase pancreaticobiliary ductal pressure. Agents that dissolve protein plugs can provide relief from or prevent symptoms. In the present study, drugs reportedly effective for pancreatic and biliary stones were used in dissolution tests. Protein plugs were obtained from choledochal cysts during surgery in two children (5- and 6-year-old girls). Plugs approximately 2 mm in diameter were immersed in citric acid, tartaric acid, dimethadione, bromhexine, dehydrocholic acid, sodium citrate, hydrochloric acid, and sodium hydroxide solutions under observation with a digital microscope. The pH of each solution was measured using a pH meter. Plugs dissolved in citric acid (5.2 mM; pH 2.64), tartaric acid (6.7 mM; pH 2.51), dimethadione (75 mM; pH 3.70), hydrochloric acid (0.5 mM; pH 3.13), and sodium hydroxide (75 mM; pH 12.75) solutions. Plugs did not dissolve in dimethadione (7.5 mM; pH 4.31), bromhexine (0.1%; pH 4.68), dehydrocholic acid (5%; pH 7.45), and sodium citrate (75 mM; pH 7.23) solutions. Protein plugs in choledochal cysts are dissolved in acidic and basic solutions, which may eliminate longitudinal electrostatic interactions of the lithostathine protofibrils.

ALCOHOLIC ACUTE PANCREATITIS OR IDIOPATHIC PANCREATITIS

Purpose: Unlike gallstones, acute intake of alcohol is believed not to be a cause of acute pancreatitis. Based on the current accepted mechanism in which alcohol causes acute pancreatitis, chronic intake daily of over 50 grams per day over many years is expected to cause chronic damage, protein plugs, fibrosis, and/or ductal changes prior to any attack of acute pancreatitis. While many patients with acute pancreatitis attributed to alcohol have evidence of chronic pancreatitis at admission, such as exocrine insufficiency, ductal changes in the pancreas and/or calcifications, the diagnosis is often made in patients with no evidence of chronic disease. In these patients, with alcoholic acute pancreatitis, the diagnosis is made based on the absence of gallstones, a normal triglyceride level and a strong history of alcohol intake despite an otherwise normal appearing pancreas. Methods: In order to better establish whether patients with acute pancreatitis attributed to alcohol, in the absence of imaging evidence of chronic disease, are indeed due to alcohol, we performed the following study. A consecutive series of patients seen in 1998 for acute pancreatitis were studied. Results: During the study period, 165 patients were admitted with acute pancreatitis. Of these, 58 were diagnosed as having alcohol as the etiology. 38/58 patients were found to have no evidence of chronic pancreatic disease on imaging, CT and/or MRI. Nine of these 38 patients were identified on follow-up, mean 9.6 years. Of these nine patients with acute pancreatitis attributed to alcohol based on history almost 10 years prior, 7/9 had no further episodes of acute pancreatitis. 5/9 patients described themselves as abstinent from alcohol use. 4/5 continued using alcohol in moderation 3/5, or heavily 1/5. Imaging had been performed within the past year in 6/9. There was no evidence of chronic pancreatitis in any of these patients defined by ductal abnormalities and/or calcifications. 3/9 of these patients had evidence of gallstones on imaging. None of the patients had any evidence of pancreatic exocrine insufficiency. Conclusion: Although there was limited follow-up, this study suggests that many patients, perhaps most patients with alcoholic acute pancreatitis may have another etiology such as gallstones. Despite a history of alcohol consumption, it remains unclear whether alcohol causes acute pancreatitis in the absence of evidence of chronic pancreatic disease at admission.

Plant- and stimulus-specific variations in remote-controlled sieve-tube occlusion

Phloem injury triggers local sieve-plate occlusion including callose-mediated constriction and protein plugging of sieve pores. In intact plants, reversible sieve-plate occlusion is induced by electric potential waves (EPWs)—accompanied by Ca2+-influx—as result of distant burning. Here, we present additional results which pertain to (a) the variability of EPW-profiles in relation to forisome conformation in intact Vicia faba plants and (b) the differential occlusion reactions to burning and cutting in various plant species. A correlation between stimulus perception and mode of phloem loading is discussed.Addendum to: Furch ACU, Hafke JB, Schulz A, van Bel AJE. Ca2+-mediated remote control of reversible sieve-tube occlusion in Vicia faba. J Exp Bot 2007; 58:2827-38.

Recent Developments in the Treatment of Alcoholic Chronic Pancreatitis

Chronic pancreatitis is a progressive inflammatory condition characterized by repeated attacks of abdominal pain, and the destruction and fibrosis of the pancreatic parenchyma which causes to reduced exocrine and endocrine functions. Alcohol is the most common cause of chronic pancreatitis. Although abstinence is usually considered a prerequisite for successful treatment of alcoholic chronic pancreatitis, we often encounter patients who have repeated attacks from the compensated stage through the transitional stage. In alcoholic chronic pancreatitis, continued alcohol consumption causes changes in the digestive hormones and vagal nerve function that induce the pancreatic acinar cells to oversecrete protein, increasing the protein concentration and viscosity of the pancreatic juice. This induces protein sedimentation from the pancreatic juice and formation of protein plugs within the pancreatic duct, triggering repeated attacks of acute pancreatitis. The treatment of alcoholic chronic pancreatitis includes alleviation of symptoms, particularly abdominal pain, elimination of trigger factors, prevention of recurrence and disease progression, adjuvant therapies for pancreatic exocrine and endocrine failure. Recently, the main constituent proteins in these protein plugs have been identified, enabling trials of several therapies, such as the administration of secretin formulations and endoscopic removal. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for the pancreatic acinar cells, inducing them to secrete pancreatic juice of low viscosity. In this review, we summarize the most recent thoughts about alcoholic chronic pancreatitis, and the new treatments, and in particular, we present our findings concerning the efficacy of bromhexine hydrochloride in the treatment of this disease.

Fatty acid calcium stones in patients with pancreaticobiliary maljunction/choledochal cyst as another cause of obstructive symptoms besides protein plugs

Symptoms of choledochal cysts are caused by protein plugs, which clog up in the long common channel and increase pancreaticobiliary ductal pressure. We report that fatty calcium acid stones/debris are another previously unreported cause of obstructive symptoms in 2 cases with choledochal cyst.

Endoscopic sphincterotomy is a useful preoperative management for refractory pancreatitis associated with pancreaticobiliary maljunction

Background Pancreatitis associated with pancreaticobiliary maljunction (PBM) is commonly treated nonoperatively before surgery. It is, however, sometimes uncontrollable, and little has been reported about the management. Methods Focusing on the preoperative management, we reviewed clinical courses of 4 PBM cases (ages 1 to 7 years old). Each had pancreatitis that was totally resistant to medical treatment and was applied endoscopic sphincterotomy (ES). Results The first case underwent percutaneous transhepatic catheter drainage (PTCD) primarily. In spite of daily lavage using the drainage tube for a week, plugs located in the common channel were not removed, and clinical findings were not improved. Therefore, ES followed by removal of protein plugs was performed to improve pancreatitis dramatically. Through this experience, 3 subsequent cases with refractory pancreatitis all underwent successful ES primarily soon after the medical treatments turned out to be ineffective. In all 4 cases, protein plugs were impacted in common channels, and ES could successfully remove the plugs that were impossible to remove by using PTCD. Improved preoperative pancreaticobiliary decompression by ES shortens the duration of recalcitrant acute pancreatitis associated with PBM allowing for a subsequent safe operation. Conclusions Endoscopic sphincterotomy is one of the useful preoperative managements for refractory pancreatitis associated with PBM.

Lymphoplasmacytic sclerosing pancreatitis forming a localized mass: a variant form of autoimmune pancreatitis

To elucidate the correlation of autoimmune pancreatitis (AIP) and mass-forming pancreatitis, in which a localized mass is formed in the pancreas. Nine cases of mass-forming pancreatitis were divided into two groups, one consisting of cases that met the histological diagnostic criteria for AIP by the Japan Pancreas Society (JPS) and the other consisting of cases which did not. Histological findings, immunohistological findings, and pancreatograms were compared between these groups. Six cases met the histological criteria of JPS (group A) and the other three did not (group B). In the mass-forming portion in group A, the wall of the pancreatic duct showed marked thickening. However, the epithelium was well preserved, and dilatation of the branch ducts or protein plugs were rarely observed. All cases showed marked obliterative phlebitis. The IgG4 labeling index (LI) was 25% or more in all but one case. In the portion other than the mass, the lobular structure was well preserved and the IgG4 LI was less than 10%. The pancreatogram showed localized stenosis or obstruction at the site of the mass associated with a normal-appearing main pancreatic duct in the remaining portion. In group B, histological findings typical of chronic pancreatitis with dilated branch ducts and protein plugs were observed. Obliterative phlebitis was not confirmed. The IgG4 LI in the mass-forming portion was low (2.3%-11.1%). There exists a subgroup of AIP showing localized mass formation and stenosis or obstruction of the main pancreatic duct with prominent obliterative phlebitis associated with a normal ductal segment.

Groove pancreatitis associated with true pancreatic cyst

We report a case of groove pancreatitis (GP) associated with a true pancreatic cyst. An 81-year-old man who had suffered epigastric pain for 4 months was referred to Saisekai Kure Hospital. Computed tomography and endoscopic retrograde pancreatography showed a cystic lesion in the groove area of the pancreas. Serum amylase elevation and imaging findings suggested GP due to the cyst. Six weeks of medical treatment did not improve the clinical symptoms. Therefore, pancreatoduodenectomy was performed. Histologic examination revealed a true cyst with intraluminal necrosis, which produced a protein plug that obstructed the Santorini duct. The parenchyma surrounding the groove area showed marked fibrosis and inflammatory cell infiltration. GP due to true pancreatic cyst was diagnosed. Although GP is usually caused by overconsumption of alcohol, which leads to changes in the pancreatic juice and the ultimate blockage of pancreatic outflow, the histologic features in our patient suggest that true pancreatic cyst stands as a secondary cause of GP.

Ca2+-mediated remote control of reversible sieve tube occlusion in Vicia faba

According to an established concept, injury of the phloem triggers local sieve plate occlusion including callose-mediated constriction and, possibly, protein plugging of the sieve pores. Sieve plate occlusion can also be achieved by distant stimuli, depends on the passage of electropotential waves (EPWs), and is reversible in intact plants. The time-course of the wound response was studied in sieve elements of main veins of intact Vicia faba plants using confocal and multiphoton microscopy. Only 15-45 s after burning a leaf tip, forisomes (giant protein bodies specific for legume sieve tubes) suddenly dispersed, as observed at 3-4 cm from the stimulus site. The dispersion was reversible; the forisomes had fully re-contracted 7-15 min after burning. Meanwhile, callose appeared at the sieve pores in response to the heat shock. Callose production reached a maximum after approximately 20 min and was also reversible; callose degraded over the subsequent 1-2 h. The heat induction of both modes of occlusion coincided with the passage of an EPW visualized by electrophysiology or the potential-sensitive dye RH-414. In contrast to burning, cutting of the leaf tip induced neither an EPW nor callose deposition. The data are consistent with a remote-controlled occlusion of sieve plates depending on the longitudinal propagation of an EPW releasing Ca(2+) into the sieve element lumen. It is hypothesized that forisome plugs and callose constriction are removed once the cytosolic calcium level has returned to the initial level in those sieve tubes.