[IMPACT OF RONCOLEUKIN ON BALANCE OF CYTOKINS IN COMPLEX TREATMENT OF OBTURATION JAUNDICE OF NONTUMORAL GENESIS].

The results of surgical treatment of 137 patients, suffering obturation jaundice of non-tumoral etiology, were analyzed. In all the patients the cause of obturation jaundice was choledocholithiasis. Roncoleukin was infused intravenously additionally in a complex of therapy. A degree of hepatic dysfunction was determined, taking into account the cholestasis markers. In 23 patients purulent cholangitis have occurred on background of obturation jaundice. Concentration of cytokins TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10 in sera were determined, using immunoassay analysis. The cytokins dysbalance severity preoperatively and dynamics of its changes have depended upon the hepatic dysbalance degree and presence of purulent cholangitis; a dysbalance is deeper, when the hepatic dysfunction is higher. Application of pathogenetically substantiated purposeful cytokinotherapy, including roncoleukin, have promoted the cytokins dysbalance elimination and improvement of the patients treatment results.

Immunoglobulin G4-related sclerosing cholangitis mimicking hilar cholangiocarcinoma diagnosed with following bile duct resection: report of a case.

We report a rare case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis without other organ involvement. A 69-year-old-man was referred for the evaluation of jaundice. Computed tomography revealed thickening of the bile duct wall, compressing the right portal vein. Endoscopic retrograde cholangiopancreatography showed a lesion extending from the proximal confluence of the common bile duct to the left and right hepatic ducts. Intraductal ultrasonography showed a bile duct mass invading the portal vein. Hilar bile duct cancer was initially diagnosed and percutaneous transhepatic portal vein embolization was performed, preceding a planned right hepatectomy. Strictures persisted despite steroid therapy. Therefore, partial resection of the common bile duct following choledochojejunostomy was performed. Histologic examination showed diffuse and severe lymphoplasmacytic infiltration, and abundant plasma cells, which stained positive for anti-IgG4 antibody. The final diagnosis was IgG4 sclerosing cholangitis. Types 3 and 4 IgG4 sclerosing cholangitis remains a challenge to differentiate from cholangiocarcinoma. A histopathologic diagnosis obtained with a less invasive approach avoided unnecessary hepatectomy.

Increased levels of sperm protein 17 mRNA and circulating antibodies in periampullary carcinoma patients.

BACKGROUND: Present-day diagnostic modalities for detecting periampullary carcinoma are suboptimal, and currently used proven markers lack specificity and sensitivity. METHODS: In order to assess the diagnostic potential of sperm protein 17, a cancer testis antigen, quantitative real-time PCR was performed to evaluate the expression of sperm protein 17 in tissue and sera specimens collected from periampullary carcinoma patients and normal subjects. Additionally, circulating levels of anti-sperm protein 17 antibodies were determined in sera of periampullary carcinoma patients and normal subjects using ELISA. RESULTS: Aberrant expression of sperm protein 17 was found in 14/15 (93 %) periampullary cancer tissues when compared with distant matched nonmalignant tissues (P = 0.006, Mann-Whitney U test). None of the distant matched nonmalignant tissues showed increased expression of sperm protein 17 mRNA. Area under the curve, sensitivity, and specificity were 0.791, 87, and 73 %, respectively. Increased levels of sperm protein 17 mRNA were demonstrated in sera of periampullary carcinoma patients (P = 0.020, Student's t test). Circulating levels of anti-sperm protein 17 antibody were found to be significantly elevated in 27/30 (90 %) periampullary carcinoma patients (P < 0.001, Student's t test). Area under the curve, sensitivity, and specificity were 0.954, 86.7, and 96.3 %, respectively. Only two of the normal subjects (7 %) showed elevated levels of anti-sperm protein 17 antibody. CONCLUSION: For the first time, our findings suggest that high levels of sperm protein 17 mRNA as well as increased circulating anti-sperm protein 17 antibodies can be used to distinguish periampullary cancer patients from healthy individuals, highlighting the diagnostic potential of sperm protein 17.

Clonal identity and histologic difference in peripheral T-cell lymphoma with follicular helper T-cell phenotype simultaneously occurring at common bile duct and lymph nodes.

We present the first case of peripheral T-cell lymphoma, not otherwise specified expressing follicular helper T-cell markers with different histologic features simultaneously involving the common bile duct and pericholedochal lymph nodes in a 72-year-old woman patient. Abdominal computed tomography revealed a localized wall thickening in the common bile duct. With the impression of cholangiocarcinoma, pancreaticoduodenectomy was done. Microscopically, dense small lymphoid cells with only minimal cytologic atypia were observed with occasional lymphoepithelial-like lesions, whereas many atypical large cells infiltrated the pericholedochal lymph nodes. Immunohistochemically, most small cells in the bile duct and the large atypical cells in the lymph nodes were all reactive for follicular helper T-cell markers including CD4, PD-1, and CXCL-13. BIOMED-2 based polymerase chain reaction using the DNA template from either the bile duct lesion or the lymph node revealed identical but different dominant clonal peaks, indicating these 2 lesions represent a spectrum of the same disease.

Biliary tract involvement in autoimmune pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a unique clinical entity that has been recently proposed, and it is frequently associated with bile duct stricture. The aim of this study was to investigate the pathophysiology of the biliary tract involvement in patients with AIP. METHODS: We evaluated the clinicopathologic findings in 16 patients with AIP. Surgical resection was performed in 7 of the patients because of suspicion of a pancreatic tumor; 8 of the other patients were treated with oral prednisolone (PSL) therapy, and the remaining patient was observed clinically and not treated. The pancreas, bile duct, and gallbladder in the surgical cases were examined histologically and immunohistochemically. We also assessed the clinical manifestations and diagnostic imaging findings before and after oral PSL therapy in the 8 patients treated with PSL. RESULTS: Stricture of the extrahepatic bile duct was detected in 88% (14/16) of the patients. Thickening of the bile duct wall was detected in 94% (15/16), and thickening of the gallbladder wall was observed in 56% (9/16). Histologically, the bile duct and gallbladder wall were characterized by diffuse lymphoplasmacytic infiltration and marked interstitial fibrosis. Immunohistochemically, the diffusely infiltrating cells consisted of predominantly CD8- or CD4-positive T lymphocytes and IgG4-positive plasma cells. These findings were the same as in the inflammatory process that was observed in the pancreas. After oral PSL therapy, the pancreatic enlargement and irregular narrowing of the main pancreatic duct improved to almost their normal size in all 8 patients; however, stricture of the extrahepatic bile duct persisted in 4 of the patients (57%, 4/7) in whom it was detected before PSL therapy. CONCLUSIONS: Based on the pathophysiologic and histologic findings and the response to PSL therapy, the biliary involvement in AIP developed by the same mechanism as the pancreatitis. CD8- and CD4-positive lymphocytes and IgG4-positive plasma cells may play an important role in the pathogenesis of AIP.

Analysis of human common bile duct-associated T cells: evidence for oligoclonality, T cell clonal persistence, and epithelial cell recognition.

The phenotype of T cells associated with the common bile duct (CBD) is unknown. We investigated the hypothesis that they behave like other intraepithelial lymphocytes (IEL). Thus, we sought to determine the phenotype, TCR repertoire, and epithelial recognition of T cells obtained during endoscopic retrograde cholangiopancreatography. Three subjects were studied: two with primary sclerosing cholangitis and one normal control. After establishing a short-term T cell line, cells were 1) stained with mAbs for flow cytometric analysis, 2) analyzed for TCRB chain transcript expression, and 3) used as effector cells for cytotoxicity and proliferation. Flow cytometry revealed that for all the subjects 98% of the T cells were TCR-alpha beta-positive. Immunohistology of the CBD showed that the epithelium and lamina propria contained significant numbers of CD3+ CD43+ CD45RO+ lymphocytes. Complementarity-determining region 3 length displays suggested that the CBD-derived lines were oligoclonal. This was confirmed by cloning and random sequencing of PCR amplification products using TCRBV region family-specific primers; TCRB chain sequences were reiterated in all transcripts analyzed. In one case, two expanded TCRB clones could be identified that were persistent in the bile duct over a 1-yr period. The CBD-derived lines were cytolytic in a redirected lysis assay and caused cytolysis of an intestinal epithelial cell line (Caco-2). This recognition was likely preferential for intestinal epithelial cells, since a CBD-derived line exhibited proliferation to two intestinal epithelial cell lines (HT-29 and Caco-2) but not three other lines (HepG2, human foreskin fibroblast, and KD). We conclude that the CBD contains IELs that share several characteristics with intestinal IELs.

Experimental foreign-body infection in the biliary tract in rats.

BACKGROUND: Biomaterials used for biliary drainage may potentially result in biomaterial-associated infections. METHODS: Foreign-body infection in the biliary tract was investigated in rats. Rubber drain pieces were implanted in the biliary tract in rats for 1-4 weeks, followed by challenges with 10(2) to 10(4) colony-forming units (cfu) Escherichia coli injected into the common bile duct. The rate of infection was calculated, the bacterial growth in the biliary tract was observed over 72 h after challenges, and the opsonic activity in bile and in sera was assessed. RESULTS: In the group with drain material, inocula as small as 10(2) cfu produced persisting infection in the common bile duct in 90% of animals, whereas the same number of E. coli infected only 30% of rats in the control and sham implantation groups (p < 0.01, chi-square test). Complement-mediated opsonic activity in bile of animals with implanted drain pieces gradually decreased with time, whereas opsonic activity in sera from the same animals remained unchanged. CONCLUSIONS: Implants in the biliary tract impair local host defense, resulting in an increased susceptibility to microbial infection.

In vitro duct-like structure formation after isolation of bile ductular cells from a murine model.

The epithelium of the biliary tree is involved in the response to numerous liver disease processes including immunologic destruction during liver transplant rejection and liver graft-versus-host disease after bone marrow transplantation. Furthermore, very little is known concerning the function of this previously inaccessible epithelium, because attempts to isolate and culture biliary cells have been unsuccessful until recently. We present a method for the isolation and culture of bile ductular cells from mice with external bile duct obstruction. Over 85% of the isolated cells stain positive for cytokeratin 19, which is characteristic of murine biliary epithelium. Incubation with recombinant murine gamma-interferon resulted in increased class II antigen expression on the isolated cell surface. When these cells were placed, on a basement membrane matrix, they formed duct-like structures composed of cells that had the morphologic characteristics of bile ductular epithelium when examined by transmission electron microscopy. The ability to isolate murine biliary epithelium that forms duct-like structures will be useful for the in vitro study of biliary epithelial characteristics and injury.

Experimental chronic non-suppurative destructive cholangitis in rabbits following immunization with bile duct antigen.

Experimental chronic non-suppurative destructive cholangitis induced in rabbits following immunization with bile duct antigen. Histological changes similar to chronic non-suppurative destructive cholangitis were induced in rabbits by sensitization with antigen prepared from bovine gallbladder mucous membrane. The occurrence of these pathological changes was significantly higher in female animals than in males: 11 out of 14 female rabbits and 4 among 11 male rabbits exhibited histological changes. Immunoprecipitation using gel-diffusion and histological analysis by an immunofluorescence technique showed that this antigen was localized exclusively in the bile duct but not in either hepatocytes or other tissues. It is suggested that histological changes induced following immunization with bile duct antigen are specific immunological phenomena. This interesting experimental model may be helpful in explaining the pathogenesis of primary biliary cirrhosis.

[Hepatitis B surface antigen in the liver and pericholedochal lymph nodes in chronic hepatitis and cirrhosis of the liver]. / Poverkhnostnyi antigen gepatita B v pecheni i perikholedokheal'nykh limfaticheskikh uzlakh pri khronicheskom gepatite i tsirroze pecheni.

Morphological characteristics of the liver and the presence of HBsAg in the blood serum, liver tissue, and pericholedocheal lymph nodes were examined in 25 patients with chronic liver diseases and 2 asymptomatic carriers of HBsAg. The antigen in tissues was demonstrated by indirect immunofluorescence and histochemically by staining with alcohol-arsein and aldehyde-fuxin. The antigen was found in the blood, liver tissue, and hepatocyte cytoplasm in both carriers and 10 patients. In 5 patients with liver cirrhosis and HBsAg antigenemia the antigen was also found in the liver tissue, in 1 patient it was absent in the blood but found in the liver, and in 2 patients it was absent in the blood and in the liver. In 5 patients with chronic hepatitis the antigen was demonstrated in the blood serum and the liver, in 12 patients it was not detected either in the blood or in the liver. In 8 patients enlarged pericholedocheal lymph nodes were examined, and in 6 of them HBsAg was detected in macrophages of the lymph nodes.

Distribution of immunoglobulin and secretory component containing cells in chickens.

Distribution of immunoglobulin (Ig)-containing cells and secretory component in internal organs of two 15-day-old embryos and 17 chickens, 1 to 480 days old, were examined by fluorescent antibody technique. In 15-day-old embryos, Ig-containing cells were not found in gut, bursa, spleen, or thymus. The bursa of Fabricius synthesized IgM, IgG, and IgA in as young as 1-day-old chicks. In extrabursal organs, IgM-containing cells were already present in intestine of 1-day-old chicks, but IgA-containing cells appeared in intestine, thymus, and spleen between the 3rd and 7th day after hatching. Very few IgG-containing cells were in intestine on the 3rd and 7th day after hatching. Secretory component was found in epithelial surfaces of intestine and ductus choledochus of most chickens examined. The presence of secretory component and IgA-containing cells in intestine supported the existence of secretory-immunologic system in chickens.

[Application of the immunofluorescente (fluorescent antibody technique) in clinical immunology.--II. Application and significance (author's transl)]. / Die Anwendung der Immunfluoreszenz (fluoreszierende Antikörpertechnik) in der klinischen Immunologie II. Befunde und ihre Bedeutung

The fluorescent antibody technique is nowadays mainly a technique, which is routinely carried out in all clinical-immunological laboratories. The main fields of application in clinical immunology are the determination of autoantibodies (e.g. ANA, AMA, smooth muscle antibodies, parietal cell antibodies), detection of B-lymphocytes as well as bacterial antigens (e.g. Treponema pallidum). Furthermore the demonstration of deposits of immune complexes in tissues (e.g. glomerulonephritis, periarteriitis nodosa). The presented paper shows the different fields of application of the fluorescent antibody technique. It is pointed out that the FAT could be only one out of the variety of methods in clinical-immunological investigations.