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PSC
Terms modified by PSC Selected AbstractsPrimary sclerosing cholangitis as a cause of false positive bile duct brushing cytology: Report of two cases.DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2005Lester J. Layfield M.D. Abstract Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by ongoing inflammation, destruction, and fibrosis of intrahepatic and extrahepatic bile ducts. Irregular narrowing and dilation of the biliary duct system produces the characteristic beaded pattern seen on cholangiogram. Malignant degeneration resulting in cholangiocarcinoma is a well-recognized sequela of PSC. Bile duct brushing cytology is the primary screening technique for cholangiocarcinoma. It is associated with a relatively low sensitivity but high specificity. Few false positive bile duct brushings have been reported in the literature, with the majority of these having occurred in a background of PSC. We report two patients with PSC in whom bile duct brush cytologies were falsely positive for carcinoma. Diagn. Cytopathol. 2005;32:119,124. © 2005 Wiley-Liss, Inc. [source] Carcinoma of the gall-bladder associated with primary sclerosing cholangitis and ulcerative colitisDIGESTIVE ENDOSCOPY, Issue 1 2000Mitsuru Seo A 64-year-old Japanese male was admitted to Fukuoka University Hospital to undergo further examination for an elevated ,-glutamyltransferase (,-GTP) level. Endoscopic retrograde cholangiography (ERC) showed dilatation of the intrahepatic bile duct and stenosis of the proximal portion of the common bile duct. No abnormality was found in the gall-bladder. Since the fecal occult blood test was positive, sigmoidoscopy and a barium enema were performed. Sigmoidoscopy showed a hyperemic and hemorrhagic mucosa in the rectum, but a barium enema study did not show any abnormal findings in the entire colon. We diagnosed the patient to have primary sclerosing cholangitis (PSC) and ulcerative proctitis based on these radiological and endoscopic findings. Bloody stool and fever occurred 4 months after the first admission. The patient's colitis extended to the entire colon. Because of the failure of corticosteroid therapy, a subtotal colectomy was performed. Given that a mass was intraoperatively palpable in the gall-bladder, a cholecystectomy was simultaneously performed. In the whole resected colon, diffuse ulcerations and mucosal islands were found. Grossly, a flat polypoid lesion, measuring 2 cm in diameter, was found in the fundus of the resected gall-bladder. Sections of this lesion in the gall-bladder revealed cystic atypical glands and some atypical cell clusters invading the subserosa. The present case suggests that careful observations are needed for patients with ulcerative colitis who have an elevated ,-GTP level even if the colitis is limited to the distal colon and the serum alkaline phosphatase level is normal. [source] Estimation of the phosphorus sorption capacity of acidic soils in IrelandEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2001R. O. Maguire Summary The test for the degree of phosphorus (P) saturation (DPS) of soils is used in northwest Europe to estimate the potential of P loss from soil to water. It expresses the historic sorption of P by soil as a percentage of the soil's P sorption capacity (PSC), which is taken to be , (Alox + Feox), where Alox and Feox are the amounts of aluminium and iron extracted by a single extraction of oxalate. All quantities are measured as mmol kg soil,1, and a value of 0.5 is commonly used for the scaling factor , in this equation. Historic or previously sorbed P is taken to be the quantity of P extracted by oxalate (Pox) so that DPS = Pox/PSC. The relation between PSC and Alox, Feox and Pox was determined for 37 soil samples from Northern Ireland with relatively large clay and organic matter contents. Sorption of P, measured over 252 days, was strongly correlated with the amounts of Alox and Feox extracted, but there was also a negative correlation with Pox. When PSC was calculated as the sum of the measured sorption after 252 days and Pox, the multiple regression of PSC on Alox and Feox gave the equation PSC = 36.6 + 0.61 Alox+,0.31 Feox with a coefficient of determination (R2) of 0.92. The regression intercept of 36.6 was significantly greater than zero. The 95% confidence limits for the regression coefficients of Alox and Feox did not overlap, indicating a significantly larger regression coefficient of P sorption on Alox than on Feox. When loss on ignition was employed as an additional variable in the multiple regression of PSC on Alox and Feox, it was positively correlated with PSC. Although the regression coefficient for loss on ignition was statistically significant (P <,0.001), the impact of this variable was small as its inclusion in the multiple regression increased R2 by only 0.028. Values of P sorption measured over 252 days were on average 2.75 (range 2.0,3.8) times greater than an overnight index of P sorption. Measures of DPS were less well correlated with water-soluble P than either the Olsen or Morgan tests for P in soil. [source] High-Yield Synthesis and Electrochemical and Photovoltaic Properties of Indene-C70 BisadductADVANCED FUNCTIONAL MATERIALS, Issue 19 2010Youjun He Abstract [6, 6]-Phenyl-C61 -butyric acid methyl ester (PC60BM) is the widely used acceptor material in polymer solar cells (PSCs). Nevertheless, the low LUMO energy level and weak absorption in visible region are its two weak points. For enhancing the solar light harvest, the soluble C70 derivative PC70BM has been used as acceptor instead of PC60BM in high efficiency PSCs in recent years. But, the LUMO level of PC70BM is the same as that of PC60BM, which is too low for the PSCs based on the polymer donors with higher HOMO level, such as poly (3-hexylthiophene) (P3HT). Here, a new soluble C70 derivative, indene-C70 bisadduct (IC70BA), is synthesized with high yield of 58% by a one-pot reaction of indene and C70 at 180 °C for 72 h. The electrochemical properties and electronic energy levels of the fullerene derivatives are measured by cyclic voltammetry. The LUMO energy level of IC70BA is 0.19 eV higher than that of PC70BM. The PSC based on P3HT with IC70BA as acceptor shows a higher Voc of 0.84 V and higher power conversion efficiency (PCE) of 5.64%, while the PSC based on P3HT/PC60BM and P3HT/PC70BM displays Voc of 0.59 V and 0.58 V, and PCE of 3.55% and 3.96%, respectively, under the illumination of AM1.5G, 100 mW cm,2. The results indicate that IC70BA is an excellent acceptor for the P3HT-based PSCs and could be a promising new acceptor instead of PC70BM for the high performance PSCs based on narrow bandgap conjugated polymer donor. [source] P3HT/PCBM Bulk Heterojunction Solar Cells: Impact of Blend Composition and 3D Morphology on Device PerformanceADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Svetlana S. van Bavel Abstract The performance of polymer solar cells (PSC) strongly depends on the 3D morphological organization of the donor and acceptor compounds within the bulk heterojunction active layer. The technique of electron tomography is a powerful tool for studying 3D morphology of the layers composed of poly(3-hexylthiophene) (P3HT) and a fullerene derivative ([6,6]-phenyl-C61-butyric acid methyl ester; PCBM), especially to quantify the amount and distribution of fibrillar P3HT nanocrystals throughout the volume of the active layer. In this study, electron tomography is used to characterize P3HT/PCBM layers with different blend compositions, both before and after thermal annealing. The power conversion efficiency of the corresponding PSCs is strongly dependent on the overall crystallinity of P3HT and the way P3HT crystals are distributed throughout the thickness of the active layer. [source] Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis,HEPATOLOGY, Issue 1 2010Sanjay Y. Bangarulingam Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (HEPATOLOGY 2009.) [source] Cholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms,HEPATOLOGY, Issue 1 2008Espen Melum Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinoma (CCA). Genetic variation of natural killer cell receptor G2D (NKG2D) has been associated with cancer susceptibility. An important ligand for NKG2D, major histocompatibility complex class I chain-related molecule A (MICA), serves as a marker of cellular stress. The 5.1 allele of the gene encoding MICA has been associated with PSC. In this study, we aimed to investigate the influence of genetic variations in the NKG2D-MICA receptor-ligand pair on the risk of CCA in patients with PSC. Seven single nucleotide polymorphisms (SNPs) covering the NKG2D gene were genotyped in 365 Scandinavian PSC patients and 368 healthy controls with TaqMan technology. Genotype data on the MICA 5.1 variant were available from previous studies. Forty-nine of the PSC patients (13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs were associated with an increased risk of CCA: rs11053781 [odds ratio (OR) = 2.08, 95% confidence interval (CI) = 1.31-3.29, corrected P (Pc) = 0.011] and rs2617167 (OR = 2.32, 95% CI = 1.47-3.66, Pc = 0.0020). Carriership of the MICA 5.1 allele was associated with resistance against CCA (OR = 0.43, 95% CI = 0.20-0.95, not corrected P = 0.032). Conclusion: Our results show that genetic variants of the NKG2D receptor are associated with development of CCA in PSC patients. This suggests that interaction between NKG2D and MICA is involved in protection against CCA in PSC. Patients who are homozygous for the nonrisk alleles are unlikely to develop CCA; this finding could be helpful in identifying PSC patients with a low CCA risk. (HEPATOLOGY 2007.) [source] Fractures and avascular necrosis before and after orthotopic liver transplantation: Long-term follow-up and predictive factors,HEPATOLOGY, Issue 4 2007Maureen M. J. Guichelaar With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. Conclusion: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients. (HEPATOLOGY 2007.) [source] Peptide antibiotic human beta-defensin-1 and ,2 contribute to antimicrobial defense of the intrahepatic biliary treeHEPATOLOGY, Issue 4 2004Kenichi Harada Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD-1 and hBD-2 were assayed in specimens of bile. hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic biliary obstruction (EBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with normal hepatic histology. hBD-2 expression was evident in bile ducts exhibiting active inflammation. Serum C reactive protein levels correlated with biliary epithelial expression of hBD-2. Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis. Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined. Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1, or tumor necrosis factor-,. In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexisting component of the biliary antimicrobial defense system. Supplementary material for this article can be found on the Hepatology website (http:/interscience.wley.com/jpages/0270,9139/suppmat/index.html). (Hepatology 2004;40:925-932). [source] BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitisHEPATOLOGY, Issue 3 2004Christiane Pauli-Magnus Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are characterized by a cholestatic pattern of liver damage, also observed in hereditary or acquired dysfunction of the canalicular membrane transporters bile salt export pump (BSEP, ABCB11) and multidrug resistance protein type 3 (MDR3, ABCB4). Controversy exists whether a genetically determined dysfunction of BSEP and MDR3 plays a pathogenic role in PBC and PSC. Therefore, 149 healthy Caucasian control individuals (control group) were compared to 76 PBC and 46 PSC patients with respect to genetic variations in BSEP and MDR3. Sequencing spanned ,10,000 bp including promoter and coding regions as well as 50,350 bp of flanking intronic regions. In all, 46 and 45 variants were identified in BSEP and MDR3, respectively. No differences between the groups were detected either in the total number of variants (BSEP: control group: 37, PBC: 37, PSC: 31; and MDR3: control group: 35; PBC: 32, PSC: 30), or in the allele frequency of the common variable sites. Furthermore, there were no significant differences in haplotype distribution and linkage disequilibrium. In conclusion, this study provides an analysis of BSEP and MDR3 variant segregation and haplotype structure in a Caucasian population. Although an impact of rare variants on BSEP and MDR3 function cannot be ruled out, our data do not support a strong role of BSEP and MDR3 genetic variations in the pathogenesis of PBC and PSC. (HEPATOLOGY 2004;39:779,791.) [source] Primary sclerosing cholangitis in children: A long-term follow-up studyHEPATOLOGY, Issue 1 2003Ariel E. Feldstein Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 ± 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated ,-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P < .001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P = .2) or medical therapy (P = .2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome. [source] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation in JapanHEPATOLOGY RESEARCH, Issue 2007Satoshi Yamagiwa Although there was some initial controversy, there is now a consensus that primary biliary cirrhosis (PBC) does indeed recur in both cadaveric and living donated allografts. Recurrence rate after deceased donor liver transplantation (LT) was reported to be 10.9,23% at 5 years. In the present study, we reviewed 221 PBC patients who underwent living-donor liver transplantation (LDLT) in Japan. The 5-year overall survival rate was 79%, and the rate of recurrence based on histological findings was 10% (7/70) after a median time of 36 months. Primary immunosuppression, withdrawal of corticosteroids and human leukocyte antigen matches were not associated with the recurrence. Recurrent PBC appears to have little impact on graft function and survival, but this may become a greater problem with longer follow up. It is noteworthy that the 10-year survival of primary sclerosing cholangitis (PSC) patients who underwent LDLT wasfound to be only 39.1% in Japan, whereas that of PBC was 72.9%. Factors associated with the poor prognosis include biliary strictures, hepatobiliary and colorectal malignancies, and recurrence of PSC. In our study, we reviewed 66 patients with PSC who underwent LDLT in Japan. The 5-year survival rate was 72%, and the rate of recurrence diagnosed on histological and cholangiographic findings was 25% (11/44). Well-defined diagnostic criteria and longer studies are required to characterize the nature of recurrent PSC and its impact on graft survival in more detail. [source] Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2010Udayakumar Navaneethan MD Abstract Abstract: Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated. (Inflamm Bowel Dis 2010) [source] Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 3 2010Ashwin N. Ananthakrishnan MD Abstract Background: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%,10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. Methods: This was a retrospective, case,control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey,Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (,1.33, 95% confidence interval [CI] 95% CI ,1.85 to ,0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010) [source] Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitisINFLAMMATORY BOWEL DISEASES, Issue 2 2010Brita Ardesjö PhD Abstract Background: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. Methods: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. Results: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. Conclusions: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen. Inflamm Bowel Dis 2009 [source] Two distinct groups of colorectal cancer in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2009Stephan Brackmann MD Abstract Background: The histological variability in colitis-associated colorectal cancer (CRC in inflammatory bowel disease [IBD]) and the association to clinical factors is unknown. Methods: In population-based material including 67 patients with CRC in IBD, histopathology of the cancers and tissue samples from different colorectal localizations were reevaluated, and relationships to clinical factors analyzed. Results: Forty-three of 60 patients (75%) showed dysplasia in the colorectum apart from the cancer, while 17 (25%) had no dysplasia at cancer diagnosis. Mean age at onset of IBD was 22 years in patients with and 34 years in patients without dysplasia (P = 0.01). The mean duration of colitis-CRC interval was 21 years in patients with and 16 years in patients without dysplasia (P = 0.02). The latter group included all patients with a colitis-CRC interval <10 years. Active inflammation was more likely to occur in patients with dysplasia (odds ratio [OR] 4.2). The 2 groups were not discriminated by gender, family history of CRC or IBD, diagnosis of PSC, medical treatment, active symptoms, or histological features like type of cancer and differentiation. In multiple logistic regression analysis the age at onset of IBD was the strongest predictive variable for dysplasia at cancer diagnosis (P = 0.025). Conclusions: Widespread neoplasia occurs in the majority of cases with CRC in IBD and is associated with early onset of IBD. Localized neoplasia occurs in about a quarter of the patients and shows an association with late-onset IBD. The 2 groups probably represent different pathogenetic entities of neoplasia in IBD. This might have consequences for surveillance strategies. (Inflamm Bowel Dis 2008) [source] Assessment of bioactive and bio-adhesive therapies to enhance stem cell attachment to root surface dentineINTERNATIONAL ENDODONTIC JOURNAL, Issue 7 2009M. A. Elseed Abstract Aim, To compare bioactive and bio-adhesive therapies to enhance stem cell attachment to the root dentine of human teeth. Methodology, Dentine slabs (n = 72) were cut from the lower 3 mm of the roots of extracted human permanent teeth. The root dentine slabs were untreated, or coated with bio-adhesive, or human recombinant transforming growth factor-beta1 (hrTGF-B1), or human recombinant bone morphogenic protein-2 (hrBMP-2). The dentine slabs were placed with the root surface in contact with confluent periodontal stem cell (PSC) cultures using aseptic techniques. The cells and dentine slabs were submerged in culture media for 4, 24 and 72 h. The specimens were fixed in formalin, dehydrated and processed for scanning electron microscopy (SEM). Results, SEM micrographs at ×2000 magnification revealed PSC extensive adherence to root dentine for all of the bio-adhesive and bioactive treatments. The addition of bioactive molecules did not improve PSC attachment. Few cells attached to the negative control treatments. Conclusions, Bio-adhesive and bioactive growth factors were not needed to promote PSC attachment to the root dentine of human teeth, because it already appears to have good natural properties to promote PSC attachment. This suggests PSC can be used for the clinical replantation of avulsed teeth without the need for bio-adhesive and bioactive treatments. [source] Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Atsushi Kanno Abstract Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 ,g/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer. © 2008 Wiley-Liss, Inc. [source] Synovial chondromatosis: the possible role of FGF 9 and FGF receptor 3 in its pathologyINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2000Dror Robinson Primary synovial chondromatosis (PSC) is a rare disorder of the synovium typified by cartilaginous nodule formation within the synovial membrane. Fibroblast growth factor receptor 3 (FGFR3) is a recently described specific marker of mesenchymal precartilaginous stem cells. Expression patterns of FGFR3 and its specific ligand, fibroblast growth factor 9 (FGF 9), were evaluated both in situ and in cell cultures. Histologically, cells at the periphery of the cartilage nodules express FGFR3 and PCNA ( proliferating cell nuclear antigen). Elevated levels of FGF 9, its specific ligand, have been found in synovial fluids of patients with synovial chondromatosis. Synoviocytes but not chondrocytes from affected patients express FGF9 in culture. This pattern is absent in normal synovium and cartilage. Downregulation of FGF9 may provide a possible nonoperative therapy for PSC. [source] Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2007Alicja Bauer Abstract Primary biliary cirrhosis (PBC) is an autoimmune liver disease with unknown etiology. Patients with PBC have antimitochondrial autoantibodies (AMA) and additionally 50% of them have antinuclear antibodies (ANA). A 15,amino acid fragment (DRKASPPSGLWSPAY) from the C-terminal part of the nuclear envelope glycoprotein gp210 has been proposed as one of the antigenic targets for ANA. The aim of this work was to develop an immunoenzymatic assay for determination of gp210 autoantibodies using for its binding a synthetic pentadecapeptide derived from the gp210 amino acid sequence and to determine level of these autoantibodies in sera of patients with PBC and other autoimmune liver diseases from Poland. Polystyrene microtitration plates coated with the synthetic peptide were consecutively incubated with diluted sera, anti-human immunoglobulin G (IgG) antibodies conjugated with horseradish peroxidase, and with tetramethylobenzidine. Optical density (OD) was read at 450 nm. The mean values of the intra- and interassay of variation coefficients of the test were 4.1 and 10.2%, respectively. Anti-gp210 was detected in 44% of PBC patients and in 6% of patients with PSC. The results were negative for healthy blood donors and other controls. The specificity of the test was 99%, so the anti-gp-210 autoantibodies estimated on DRKASPPSGLWSPAY can be a reliable marker of PBC. J. Clin. Lab. Anal. 21:227,231, 2007. © 2007 Wiley-Liss, Inc. [source] Synthesis and applications of low-bandgap conjugated polymers containing phenothiazine donor and various benzodiazole acceptors for polymer solar cellsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 21 2010Harihara Padhy Abstract A series of soluble donor-acceptor conjugated polymers comprising of phenothiazine donor and various benzodiazole acceptors (i.e., benzothiadiazole, benzoselenodiazole, and benzoxadiazole) sandwiched between hexyl-thiophene linkers were designed, synthesized, and used for the fabrication of polymer solar cells (PSC). The effects of the benzodiazole acceptors on the thermal, optical, electrochemical, and photovoltaic properties of these low-bandgap (LBG) polymers were investigated. These LBG polymers possessed large molecular weight (Mn) in the range of 3.85,5.13 × 104 with high thermal decomposition temperatures, which demonstrated broad absorption in the region of 300,750 nm with optical bandgaps of 1.80,1.93 eV. Both the HOMO energy level (,5.38 to ,5.47 eV) and LUMO energy level (,3.47 to ,3.60 eV) of the LBG polymers were within the desirable range of ideal energy level. Under 100 mW/cm2 of AM 1.5 white-light illumination, bulk heterojunction PSC devices containing an active layer of electron donor polymers mixed with electron acceptor [6,6]-phenyl-C61 -butyric acid methyl ester (PC61BM) or [6,6]-phenyl-C71 -butyric acid methyl ester (PC71BM) in different weight ratios were investigated. The best performance of the PSC device was obtained by using polymer PP6DHTBT as an electron donor and PC71BM as an acceptor in the weight ratio of 1:4, and a power conversion efficiency value of 1.20%, an open-circuit voltage (Voc) value of 0.75 V, a short-circuit current (Jsc) value of 4.60 mA/cm2, and a fill factor (FF) value of 35.0% were achieved. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010 [source] Identification and characterization of IgG4-associated autoimmune hepatitisLIVER INTERNATIONAL, Issue 2 2010Hobyung Chung Abstract Background: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. Aims: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. Methods: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. Results: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4-positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4-positive AIH as compared with those patients with IgG4-negative AIH. Patients with IgG4-positive AIH also showed a marked response to prednisolone therapy. Conclusions: AIH may be classified into either an IgG4-associated type or an IgG4 non-associated type with the former showing a marked response to prednisolone treatment. [source] Occult hepatitis B virus infection in patients with autoimmune liver diseasesLIVER INTERNATIONAL, Issue 3 2009Sarah P. Georgiadou Abstract Background: Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. Aims: To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. Methods: One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. Results: Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. Conclusion: Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up. [source] Liver transplantation for primary sclerosing cholangitisLIVER INTERNATIONAL, Issue 2 2000Paul J. Gow Abstract: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology that is progressive in most symptomatic patients, advancing toward cirrhosis and liver failure. Liver transplantation is the only therapeutic option for patients with end stage liver disease resulting from this disorder. The results of transplantation for PSC are excellent with one-year survival rates of 90,97% and five-year survival rates of 80,85%, but are closely related to pre-transplant Child-Pugh stage. Recurrence of PSC after liver transplantation is common, occurring in up to 20% of patients, but it appears to have little effect on patient survival, as survival of patients with recurrent PSC is similar to that of those without evidence of recurrence. Cholangiocarcinoma is a catastrophic complication of PSC and as yet no reliable screening method exists. The results of liver transplantation for patients with clinically apparent cholangiocarcinoma are extremely poor, however in patients in whom a microscopic tumour is detected in the explanted liver, survival is similar to those transplanted with PSC without cholangiocarcinoma. Activity of inflammatory bowel disease (IBD) appears to be more severe after transplantation, especially in units where steroid immunosuppression is withdrawn early. Colon cancer appears within the first few years after transplantation in approximately 7% of patients with IBD who are transplanted for PSC. Annual colonoscopy in this population seems prudent. [source] A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allograftsLIVER TRANSPLANTATION, Issue 3 2009Edward Alabraba Previously, we have found that the absence of the colon after liver transplantation (LT) protects the patient from recurrent primary sclerosing cholangitis (rPSC). As our previous observation has not been confirmed in other series, we have reviewed our cohort of patients grafted for primary sclerosing cholangitis (PSC) with greater numbers and longer follow-up to reassess the rate, consequences, and risk factors for rPSC. We collected data on patients who underwent LT for PSC between January 1986 and April 2006. Data were collected for cytomegalovirus status, inflammatory bowel disease status, time of colectomy, type of colectomy, donor-recipient gender mismatch, recipient sex, extended donor criteria (EDC), and donor risk index. Accepted criteria were used to diagnose rPSC. Of a total of 230 consecutive adult patients, 61 (27%) underwent colectomy pre-/peri-LT, and 54 (23.5%) developed rPSC at a median of 4.6 (range, 0.5,12.9) years post-LT. A total of 263 deceased donor grafts were used, and 73 were EDC grafts. A diagnosis of rPSC was made in 61 of the 263 grafts (23%). The recurrence-free patient survival was significantly better (P < 0.05) in patients who underwent pre-/peri-LT colectomy and in those with non-EDC grafts. In conclusion, in this larger cohort of 230 patients and with longer follow-up of 82.5 (range, 0.0,238.6) months [in comparison with the previous report of 152 recipients with a follow-up of 52.8 (range, 1,146) months], we have shown that colectomy remains a significant risk factor for rPSC and that colectomy before and during initial LT for PSC confers a protective effect against rPSC in subsequent graft(s). Moreover, we have shown that EDC grafts are also a significant risk factor for rPSC. Liver Transpl 15:330,340, 2009. © 2009 AASLD. [source] Current diagnosis and management of primary sclerosing cholangitisLIVER TRANSPLANTATION, Issue 6 2008Jens J. W. Tischendorf Primary sclerosing cholangitis (PSC) is an important liver disease with major morbidity and mortality. The diagnosis of PSC is confirmed by magnetic resonance cholangiopancreaticography, and endoscopic retrograde cholangiopancreaticography is performed in patients needing therapeutic endoscopy. As a result of the unknown cause of the disease, current medical therapies are unsatisfactory. Nevertheless, high-dose ursodeoxycholic acid should be recommended for treatment of PSC patients because there is a trend toward increased survival. Dominant bile duct stenoses should be treated endoscopically. However, liver transplantation continues to be the only therapeutic option for patients with advanced disease. Estimation of prognosis and timing of liver transplantation should be determined individually for each PSC patient on the basis of all results. The diagnosis and treatment of cholangiocarcinoma (CC) still remain a challenge in PSC patients. Early diagnosis of CC certainly is a prerequisite for successful treatment with surgical resection or innovative strategies such as neoadjuvant radiochemotherapy with subsequent orthotopic liver transplantation. Therefore, endoscopic techniques such as cholangioscopy and/or intraductal ultrasound may be useful diagnostic tools in patients with stenoses suspicious for malignancy. Liver Transpl 14:735,746, 2008. © 2008. [source] Recurrence of autoimmune liver disease after liver transplantation: A systematic reviewLIVER TRANSPLANTATION, Issue 12 2006Manjushree Gautam Recurrence of autoimmune liver disease in allografts has long been a topic of debate. We conducted a systematic review of the literature to examine the reported incidence of recurrence after liver transplantation of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH). The MEDLINE, EMBASE, and Cochrane electronic databases were used to identify articles. The inclusion criteria used were articles on patients with at least 90 days of posttransplantation follow-up, histologic criteria for diagnosis of PBC and AIH recurrence, radiologic or histologic criteria or both for diagnosis of PSC recurrence, and exclusion of other causes of liver disease causing similar histologic findings. Incidence in individual studies was combined to calculate the overall recurrence. Risk factors were analyzed whenever crude data were available. Funnel plots were used to assess publication bias. Out of 90 articles identified, 43 met criteria for systematic review (PBC, 16; PSC, 14; AIH, 13). The calculated weighted recurrence rate was 18% for PBC, 11% for PSC, and 22% for AIH. No difference was found in PBC and AIH recurrence by type of primary immunosuppression. There were not enough data to assess this issue in PSC studies. There was evidence of publication bias among PSC and AIH studies but not among PBC studies. In conclusion, recurrence of autoimmune liver disease after liver transplantation appears to be a real concern. As these patients are followed long-term, recurrence of disease may become the primary cause of morbidity. Liver Transpl 12:1813-1824, 2006. © 2006 AASLD. [source] The association of HLA-DR13 with lower graft survival rates in hepatitis B and primary sclerosing cholangitis caucasian patients receiving a liver transplantLIVER TRANSPLANTATION, Issue 4 2006Yasuro Futagawa We investigated an association of human leukocyte antigen (HLA)-DR13 to graft survival in liver transplantation among Caucasian recipients. 28,708 deceased liver transplants performed between January 1990 and December 2002 in the United States as reported to the United Network for Organ Sharing registry were utilized to compare survival rates. We utilized Caucasian adult patients (>20 years) by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard analyses. HLA-DR13-negative hepatitis B virus (HBV) and primary sclerosing cholangitis (PSC) recipients yielded significantly lower graft survival rates than those of DR13-negative patients (P = 0.002, P = 0.015, respectively). This negative association was still significant after adjusting potential confounding factors. The Cox test demonstrated that HLA-DR13-positive groups have a significantly higher hazard ratio in PSC (1.40; P = 0.029; 95% confidence interval, 1.04-1.90) and HBV patients (1.78; P = 0.032; 95% confidence interval, 1.05-3.02). In conclusion, our data suggest that HLA-DR13 is a strong, positive predictor of increased risk for graft loss in HBV and PSC liver transplant recipients. Further study is needed to test the hypothesis that DR13-related immune responses may play a role in mediating graft loss in HBV and PSC liver transplantations. Liver Transpl 12:600,604, 2006. © 2006 AASLD. [source] Liver transplantation for incidental cholangiocarcinoma: Analysis of the Canadian experienceLIVER TRANSPLANTATION, Issue 11 2005Peter Ghali Cholangiocarcinoma is a biliary tumor, which not infrequently complicates primary sclerosing cholangitis. It carries a poor prognosis and, with the exception of carefully selected individuals in research protocols, contraindicates orthotopic liver transplantation. There has been some suggestion that cholangiocarcinomas incidentally discovered at the time of transplantation carry a better prognosis. The goal of this retrospective study was to perform a national review of outcomes after liver transplantation in Canadian recipients found to have incidental cholangiocarcinoma in their explanted native liver. Six of the seven liver transplant centers in Canada provided clinical and follow-up information on all liver transplant recipients found to have incidental cholangiocarcinoma in their explants. The diagnosis or suspicion of cholangiocarcinoma prior to transplantation were exclusion criteria for this study. Ten individuals with cholangiocarcinoma were transplanted between 1996 and 2003. The median duration of follow-up was 28 months. Eight of the 10 had PSC. All of the tumors were stage I or II. The 3-year survival for these patients was 30%. The median time to recurrence was 26 months (95% confidence interval 13uu-uu37), and the median time to death was 30 months (95% confidence interval 28uu-uu53). In conclusion, although early survival of patients transplanted for incidental cholangiocarcinoma appears good, intermediate- and long-term survival rates are not better than for individuals historically transplanted with known cholangiocarcinoma. Aggressive investigation for cholangiocarcinoma is mandated. Incidentally found tumours remain a difficult treatment problem, and prospective adjuvant chemo-, radio-, and immunotherapies should be investigated. (Liver Transpl 2005;11:1412,1416.) [source] Transplantation for hilar cholangiocarcinomaLIVER TRANSPLANTATION, Issue S10 2004Julie K. Heimbach Key Points 1Patients with primary sclerosing cholangitis (PSC) have a 8 to 12% risk of developing cholangiocarcinoma (CCA). 2Cytologic techniques for aneuploidy such as digital image analysis and fluorescence in situ hybridization increase the detection rate for CCA. 3Survival following resection for CCA is 20% to 40% at 5 years. 4Survival following liver transplantation for unresectable, perihilar CCAs, mass lesion if present <3 cm, is greater than 80% at 5 years. 5Patients with intrahepatic CCAs are not eligible for liver transplantation. (Liver Transpl 2004;10:S65,S68.) [source] | ||||||||||||||||||||||||||||||||||