Biomedical subjects

K Tsuneyama

Publications and source records attributed to K Tsuneyama.

At least 19 recordsLinked to original sources

PubMed2006

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

Adenocarcinoma↗

PubMed2006

Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.

Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional protein. Previous studies have suggested that galectin-3 may play an important role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a liver condition that may progress to end-stage liver disease and based on the known functions of galectin-3, it was hypothesized that galectin-3 might play a role in the development of NAFLD. Thus, this study investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male mice at 6 months of age histologically displayed mild to severe fatty change. The liver weight per body weight ratio, serum alanine aminotransferase levels, liver triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were significantly increased compared with those in gal3(+/+) mice. Furthermore, the hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE (RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study suggests that the absence of gal3 can cause clinico-pathological features in male mice similar to those of NAFLD.

Alanine Transaminase↗

PubMed2003

A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis.

AIM: To examine the pathological changes of hepatic arteries in idiopathic portal hypertension (IPH) which is characterized by the obliteration of the intrahepatic portal vein branches and presinusoidal portal hypertension. METHODS AND RESULTS: Liver specimens (biopsied or surgically resected) from 20 patients with IPH, 20 patients with alcoholic fibrosis/cirrhosis (AF/C) and 20 histologically normal livers were used. The vascular lumina of arterial and venous vessels in portal tracts were morphometrically evaluated by an image analysis system. The ratio of portal venous luminal area to portal tract area (portal venous index) of IPH and that of AF/C were significantly reduced compared with normal liver. The portal venous index for IPH was significantly lower than that for AF/C. The ratio of hepatic arterial luminal area to portal tract area for AF/C was significantly higher than that in normal liver; however, that for IPH was similar to normal. The peribiliary vascular plexus was increased in AF/C but not in IPH. In AF/C, the number of mast cells and macrophages known to be the source of angiogenic substances was significantly increased in the portal tract compared with normal liver, while in IPH it was not increased. CONCLUSIONS: In AF/C, a reduction in portal venous lumen was associated with an increase of hepatic arterial lumen and of angiogenesis-related cells in portal tracts. However, such compensatory arterial changes were not evident in IPH, and this compensatory failure may be a feature of IPH.

Biopsy↗

PubMed2003

Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma.

AIMS: To investigate the participation of DMBT-1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN-L) arising in hepatolithiasis. DMBT-1 plays a role in mucosal immune defence. METHODS AND RESULTS: The expression of DMBT-1 was examined immunohistochemically in biliary epithelial cells in hepatolithiasis (n = 25), invasive and non-invasive cholangiocarcinoma associated with hepatolithiasis (n = 52), IPN-L with hepatolithiasis (n = 49), cholangiocarcinoma without hepatolithiasis (n = 32), and 10 normal control livers. DMBT-1 was expressed more frequently in the biliary epithelia of hepatolithiasis when compared with normal livers (P < 0.05). DMBT-1 expression was also frequent in IPN-L (57%) and non-invasive cholangiocarcinoma (79%). By contrast, DMBT-1 was decreased in invasive cholangiocarcinoma with and without hepatolithiasis (50% and 30%, respectively) (P < 0.05). The homozygous deletion of the DMBT-1 gene was recognized in four (20%) of 20 cholangiocarcinoma tissues and two (50%) of four cholangiocarcinoma cell lines, corresponding to the reduction of DMBT-1 expression. No deletion was detected in hepatolithiasis tissues. CONCLUSION: DMBT-1 expression is increased in IPN-L and non-invasive cholangiocarcinoma as well as in biliary epithelia in hepatolithiasis. Decreased expression of DMBT-1 and homozygous deletion of the DMBT-1 gene in invasive cholangiocarcinoma suggest that they occur in the late stage of cholangiocarcinogenesis.

Agglutinins↗

PubMed2001

Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis.

The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

Adult↗

PubMed2001

Frequent molecular identification of Campylobacter but not Helicobacter genus in bile and biliary epithelium in hepatolithiasis.

Bacterial infection of the biliary tree and bile stasis may be causally related to hepatolithiasis, but which bacterial species are involved and their roles in the pathogenesis of hepatolithiasis have not been ascertained. Recently, the Helicobacter genus was detected in human bile and biliary mucosal samples by molecular techniques, and its association with several biliary diseases has been suggested. The Campylobacter genus, which is closely related to the Helicobacter genus, has also recently been identified as causative of human gastrointestinal diseases. This study attempted to elucidate whether Helicobacter and/or Campylobacter bacteria are present in bile samples and biliary mucosal specimens from hepatolithiasis patients and whether they are involved in the pathogenesis of hepatolithiasis. The 16S rRNA gene of the Helicobacter and of the Campylobacter genus was examined by polymerase chain reaction in DNA samples extracted from bile and/or microdissected biliary epithelium from 69 patients with hepatolithiasis and control patients with choledocholithiasis, cholecystolithiasis, and normal gall bladders. The Helicobacter genus was detected in 1 of 8 (13%) biliary epithelial samples in hepatolithiasis and 1 of 10 (10%) bile samples in choledocholithiasis. The Campylobacter genus was detected in 3 of 14 (21%) bile samples and 5 of 8 (63%) epithelial samples in hepatolithiasis, and in 2 of 15 (13%) bile samples and 1 of 8 (13%) epithelial samples in cholecystolithiasis. The detection rate for Campylobacter in biliary epithelium of hepatolithiasis was significantly higher than in the bile or biliary epithelium of control groups (p<0.05). By a phylogenetic analysis based on nucleotide sequences, the Campylobacter genuses detected in hepatolithiasis were clustered with C. rectus or C. showae. The frequent detection of the Campylobacter 16S rRNA gene in bile, and especially in biliary epithelium of hepatolithiasis, suggests a pathogenetic relationship with Campylobacter infection.

Aged↗

PubMed2001

Pathology and pathogenesis of intrahepatic bile duct loss.

In recent years, the pathology and pathogenesis of bile duct loss have been extensively studied, and a number of hepatobiliary diseases have been added to the list of ductopenic diseases. In addition, the biology of biliary epithelial cells is now being studied with respect to bile duct loss, as well as biliary epithelial neoplasia. In this review, recent advances in pathogenetic and pathological studies of intrahepatic bile duct loss are described, with an emphasis on immune-mediated cholangiopathies. The bile duct loss, an acquired and pathologic process that occurs in the biliary tree, is recognizable as an absence of bile duct in an individual portad tract, and also as such absence in the vicinity of parallel running hepatic arterial branches that constitute the portal triad. Immunostaining with biliary cytokeratin and other carbohydrate materials is useful for the identification of biliary elements in the inflamed portal tracts or fibrous septa. The underlying processes responsible for bile duct loss include immunological, ischemic, infectious, metabolic, and toxic processes. Bile duct loss in primary biliary cirrhosis and primary sclerosing cholangitis is immune-mediated, that in interventional radiology using hepatic arterial branches is related to biliary ischemia, while that in hepatic allograft rejection is related to both immunological and ischemic insults. Bacterial and viral cholangitis with bile duct loss is an example of infectious cholangitis. The biliary tree maintains its homeostasis by renewal and dropout, and bile duct loss occurs mainly via biliary apoptosis. In some patients with bile duct loss, such as occurs in drug-induced injuries, the bile ducts regenerate and finally redistribute in the liver, while in other types of bile duct loss, the loss is progressive and is followed by vanishing bile duct syndrome, leading to biliary cirrhosis or liver transplantation. More analysis of the biology of biliary epithelial cells is mandatory for the evaluation of the pathobiology of bile duct loss, as well as for the effective restoration of biliary epithelial cells, in ductopenic liver diseases.

Bile Duct Diseases↗

PubMed2001

Scavenger cells with gram-positive bacterial lipoteichoic acid infiltrate around the damaged interlobular bile ducts of primary biliary cirrhosis.

BACKGROUND/AIMS: Gram-positive bacterial DNA is frequently detectable in gallbladder bile of primary biliary cirrhosis (PBC) patients. To advance these findings, lipoteichoic acid (LTA) of gram-positive bacteria with high antigenicity was examined in liver specimens and bile from PBC patients and controls. METHODS: LTA was examined by Western blotting in the gallbladder bile from 15 PBC, 11 cholecystolithiasis and six normal subjects, and by immunohistochemistry in liver specimens from 16 PBC, six primary sclerosing cholangitis (PSC), eight chronic viral hepatitis C (CVH-C) and five normal subjects. RESULTS: In the gallbladder bile, there was no significant difference in the positive rate of LTA between PBC and controls. LTA-containing mononuclear cells were frequently detected in the portal tracts, particularly around the bile ducts and in hepatic sinusoids in PBC, while they were infrequent or occasional in control livers. These LTA-containing cells were sinusoidal endothelial cells and Kupffer cells, and portal monocytes, which frequently expressed scavenger receptor class B type 1. CONCLUSIONS: LTA derived from bacterial fragments may reach the bile, not only in the diseased state but also under normal conditions. Such LTA may be involved in the development and progression of portal tract lesions, particularly bile duct lesions, in PBC.

Adult↗

PubMed2001

Oncocytic biliary cystadenocarcinoma is a form of intraductal oncocytic papillary neoplasm of the liver.

Biliary cystadenocarcinoma with oncocytic differentiation was first reported in 1992. This is a report of a second case. The patient (a 71-year-old man) was admitted to our hospital complaining of abdominal fullness. Multicystic lesions were identified in the left hepatic lobe radiologically. The patient died of peritoneal dissemination of carcinoma 20 months later. At autopsy, the tumor of the left hepatic lobe was found to be composed of adjoining multiple cystic lesions and a solid lesion with infiltration of the hepatic hilus and peritoneal dissemination. Histologically, the multicystic lesions were covered by papillary neoplastic epithelial cells with an eosinophilic granular cytoplasm resembling that of oncocytes and a fine fibrovascular core. The cyst wall was fibrous, but there was no mesenchymal stroma. In the solid lesion and infiltrated areas, acidophilic and granular carcinoma cells formed small glandular or solid cord patterns with much mucin secretion (mucinous carcinoma). Immunohistochemically, carcinoma cells of both components were found to contain many mitochondria and showed the phenotypes of hepatocytes and cholangiocytes. Interestingly, the intrahepatic biliary tree also was invaded by carcinoma cells. This may be a case of intraductal oncocytic papillary neoplasm of the left hepatic lobe followed by secondary cystic dilatation of the affected bile duct.

Adenoma, Oxyphilic↗

PubMed2001

Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis.

AIM: Biliary papillomatosis is characterized by papillary proliferations of biliary lining cells without invasion or metastasis. The neoplastic character and biological behaviour of this disease remain still speculative. These issues were examined in this study. METHODS AND RESULTS: Mucin core protein MUC1, MUC2, MUC3, MUC5AC and carbohydrate antigens (T, Tn and sialosyl Tn) were immunohistochemically examined, using 11 lesions of biliary papillomatosis from seven patients, and five lesions of biliary papillomatosis with foci of carcinoma from four patients. Five cases of papillary intrahepatic cholangiocarcinoma and 12 histologically normal livers were used as a control. Patients with biliary papillomatosis alone or with carcinoma were middle-aged or elderly (five men and six women). Microscopically, biliary papillomatosis showed a villous, papillo-tubular, papillary, or papillo-villous pattern with a thin fibrovascular core. Cytologically, they were classifiable into biliary epithelial or pyloric gland-like type. The former was frequent in the cases associated with carcinoma. Expression of MUC1, Tn antigen and sialosyl Tn antigen was frequent and marked in biliary papillomatosis alone and with carcinoma and also intrahepatic papillary carcinoma. In addition, marked expression of MUC1 and Tn antigen were rather frequent in biliary papillomatosis with carcinoma and intrahepatic biliary papillary carcinoma compared with biliary papillomatosis. MUC2 was rather frequent and marked in biliary papillomatosis alone compared to other two disease groups. Focal expression of MUC5AC and MUC2 was rather frequent and infrequent irrespective of disease group, respectively. Focal expression of T antigen was frequent in papillary ICC. CONCLUSION: Biliary papillomatosis could undergo overt malignant transformation along with altered phenotypic expression of MUC proteins and mucin carbohydrate antigens.

Aged↗

PubMed2001

Hepatocellular carcinoma arising in non-alcoholic steatohepatitis.

The incidence and significance of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH) has not been previously evaluated in detail. We recently experienced a case of NASH with multicentric HCC in a female patient. At the age of 58 years, the patient was diagnosed with non-insulin-dependent diabetes mellitus, treated by insulin therapy. The patient did not drink alcohol. She was negative for all serological markers of hepatitis B and C virus infection. Because of liver dysfunction, a needle biopsy was performed at the age of 62 years, and pathological findings, such as fatty change, Mallory's body, nuclear glycogen and pericellular fibrosis, suggested a diagnosis of NASH. Subsequently, four nodules were detected in the liver by imaging. Liver biopsies were performed from each nodule. One nodule was pathologically diagnosed as a pseudolymphoma, while three other nodules were moderately differentiated HCC (10 years after the diagnosis of non-alcoholic steatohepatitis), well-differentiated HCC (11 years later) and dysplastic nodule (11 years later), suggesting multicentric occurrence of HCC. This case suggests that HCC could be a late complication of NASH.

Biopsy, Needle↗

PubMed2001

Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma.

To investigate the molecular mechanism for enhanced fibrous stroma formation in intrahepatic cholangiocarcinoma (ICC), we surveyed the expression pattern of basement-membrane-type heparan sulfate proteoglycan (HSPG; also known as perlecan) at the core protein and the mRNA level in ICC as well as in other liver neoplasms and reactive hepatic diseases. Immunohistochemistry of paraffin-embedded liver sections with hyaluronidase pretreatment showed that HSPG was present in small amounts in normal liver around the bile ducts and the blood vessels within the portal area. There was no evident expression within the hepatic lobules. Intense immunoexpression of HSPG was seen in the tumor-specific fibro-myxoid stroma of ICC and metastatic liver cancer originating from the colon. However, tumor-specific stroma of hepatocellular carcinomas showed little or no expression of HSPG. At the mRNA level, signals for HSPG were found in tumor cells of cholangiocarcinoma and metastatic colonic carcinomas, and in myofibroblasts in the tumor fibro-myxoid-specific stroma. From immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analyses, a cultured human intrahepatic cholangiocarcinoma cell line (CCKS1), was found to express high levels of HSPG core protein and mRNA. These findings suggest that biliary and metastatic colon carcinoma cells as well as stromal myofibroblasts have a potential for HSPG production. In order to investigate the growth, invasion and metastatic ability of ICC, further study of the 'self-made' stromal component of ICC may provide a new approach.

Adult↗

PubMed2001

Spontaneous occurrence of chronic non-suppurative destructive cholangitis and antimitochondrial autoantibodies in MRL/lpr mice: possible animal model for primary biliary cirrhosis.

MRL/MP mice bearing the lymphoproliferative gene lpr (known as MRL/MP-lpr/lpr or MRL/Ipr mice) are known to spontaneously develop severe autoimmune diseases such as glomerulonephritis, arteritis and arthritis at an early stage of their life. They have also been reported to develop severe sialadenitis, suggesting that this mouse could be a model for Sjögren's syndrome. Primary biliary cirrhosis, an autoimmune disease characterized by chronic non-suppurative destructive cholangitis and the occurrence of antimitochondrial antibodies, is frequently associated with Sjögren's syndrome. In this study, we examined whether cholangitis and/or antimitochondrial antibodies occur in this mouse model, using more than 100 young and old MRL/Ipr mice. We frequently found portal inflammation associated with cholangitis of small intrahepatic bile ducts, especially in older mice. There was also infiltration of inflammatory cells (monocytes) as well as CD4-positive T cells. Epithelioid granuloma and bile-duct loss were also occasionally found. These histological features resemble primary biliary cirrhosis. In addition, antimitochondrial antibodies were shown by immunocytochemistry to be present in the sera of MRL/Ipr mice. There is currently no established animal model for primary biliary cirrhosis. Therefore, further studies on MRL/Ipr mice, with respect to pathogenesis of primary biliary cirrhosis, are warranted.

Animals↗

PubMed2001

Molecular identification of bacterial 16S ribosomal RNA gene in liver tissue of primary biliary cirrhosis: is Propionibacterium acnes involved in granuloma formation?

The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative. Epithelioid granulomas are often found in the vicinity of damaged interlobular bile ducts in PBC, raising the possibility of a reaction to microbial materials. In this study, we tried to detect and identify bacterial DNA within granulomatous lesions in PBC. Using liver sections from 9 patients with PBC and 13 control livers, granuloma in portal tracts, portal tracts without granuloma, and adjacent hepatic parenchyma were selectively microdissected from sections, and then DNA was extracted from them. First, part of the bacterial 16S ribosomal RNA (rRNA) gene was amplified from DNA samples extracted from 5 PBC and 6 control livers, and their amplicons were sequenced for the identification of bacterial species. Several indigenous bacteria were identified. Among them, Propionibacterium acnes (P. acnes) was detected as a major clone in 20% to 50% of sequenced clones from granuloma of PBC, but the detection rate of P. acnes was 0% to 20% in those cloned from adjacent hepatic parenchyma of PBC. Then, a P. acnes-specific PCR was performed using all microdissected samples. Distinct PCR products were identified in epithelioid granuloma in all 9 PBC cases. The result that P. acnes DNA is present as a major clone in granulomas of PBC, suggest that P. acnes is involved in the pathogenesis of granuloma in PBC.

DNA, Bacterial↗

PubMed2001

Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver.

Idiopathic portal hypertension (IPH) is characterized by a long-standing presinusoidal portal hypertension of unknown etiology in adults. Some unidentified agent(s) affect(s) the intrahepatic small portal veins or portal tracts. Immunological disturbance, thromboembolism, infectious etiology and/or increased fibrogenesis in portal tracts are suspected as being candidates for the primary agent(s). During the long clinical course of IPH, several pathological changes may occur, including subcapsular parenchymal atrophy, atrophy of the liver, portal and parenchymal fibrosis, and portal venous phlebosclerosis and thrombosis. The last-named of these lesions is mostly found in patients with a history of splenectomy. Subcapsular parenchymal and hepatic atrophy may result from a hepatocellular dropout via apoptosis or necrosis because of intrahepatic hemodynamic disturbances, particularly chronic portal venous blood insufficiency. Pericellular fibrosis and thin fibrous septa are also frequently found and associated with activated perisinusoidal cells positive for smooth muscle actin. At the same time, vague nodular hyperplasia of hepatocytes not surrounded by fibrous septa is not infrequently seen. It may resemble nodular regenerative hyperplasia, partial nodular transformation, or focal nodular hyperplasia. However, liver cirrhosis does not occur even at the terminal stage. Taking these findings into consideration, a new staging of IPH with a combination of hepatic parenchymal atrophy and portal venous thrombosis was proposed: non-atrophic liver without subcapsular parenchymal atrophy (stage I), non-atrophic liver with subcapsular parenchymal atrophy (stage II), atrophic liver with subcapsular parenchymal atrophy (stage III), and portal venous occlusive thrombosis (stage IV). IPH livers are likely to progress from stage I to stage III. Stage IV, which occurs relatively late, has a poor prognosis. This staging is applicable to clinical and autopsy cases without any histological data.

Adult↗

PubMed2000

Immunohistochemical analysis of cell-matrix adhesion molecules and their ligands in the portal tracts of primary biliary cirrhosis.

Intraepithelial migration of lymphoid cells (epitheliotropism) through the basement membrane of the bile duct is a key event in the development of chronic non-suppurative destructive cholangitis (CNSDC) and eventual immune-mediated bile duct loss in primary biliary cirrhosis (PBC). Cell-to-cell and cell-to-extracellular matrix proteins may play an important role in the development of CNSDC. To address the events of epitheliotropism in CNSDC, the expression of cell-matrix adhesion molecules such as integrins alpha1, alpha3, alpha4, alpha5, and alpha6 and the distribution of fibronectin, laminin, and collagen type IV were studied immunohistochemically, with emphasis on both infiltrating lymphocytes and the bile ducts, in frozen sections from 15 PBC cases and 34 controls (chronic viral hepatitis, extrahepatic biliary obstruction, and normal liver). In PBC and chronic viral hepatitis, most of the infiltrating lymphoid cells expressed integrin alpha4, while such expression was less common in extrahepatic biliary obstruction and normal liver. A biliary basement membrane-like structure was delineated by immunostaining of collagen type IV and laminin in PBC and controls. On the basement membrane of CNSDC, fibronectin, a ligand of integrin alpha4, was strongly and frequently expressed in PBC, while such expression on the biliary basement membrane was rare in other controls. These results suggest that increased fibronectin expression on the biliary basement membrane and integrin alpha4-fibronectin interaction facilitate adhesion and the penetration of infiltrating alpha4-expressing lymphocytes into the biliary epithelial layer in PBC.

Antigens, CD↗

PubMed2000

Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis.

BACKGROUND/AIMS: The etiopathogenesis of bile duct lesion in primary biliary cirrhosis is unknown, though the participation of bacteria and/or their components and products is suspected. In this study, we tried to detect and identify bacteria in the bile of patients with primary biliary cirrhosis by polymerase chain reaction using universal bacterial primers of the 16S ribosomal RNA gene. METHODS: Gallbladder bile samples from 15 patients with primary biliary cirrhosis, 5 with primary sclerosing cholangitis, 5 with hepatitis C virus-related liver cirrhosis, 11 with cholecystolithiasis, and from 12 normal adult gallbladders were used. In addition to the culture study, partial bacterial 16S ribosomal RNA gene was amplified by polymerase chain reaction (PCR) taking advantage of universal primers that can amplify the gene of almost all bacterial species, and the amplicons were cloned and sequenced. Sequence homology with specific bacterial species was analyzed by database research. Bacterial contamination at every step of the bile sampling, DNA extraction and PCR study was avoided. Furthermore, to confirm whether bacterial DNA is detectable in liver explants, the same analysis was performed using 10 liver explants of patients with primary biliary cirrhosis. RESULTS: In primary biliary cirrhosis, 75% (p<0.0001) of 100 clones were identified as so-called gram-positive cocci while these cocci were positive in only 5% in cholecystolithiasis (p<0.0001). In cholecystolithiasis gram-negative rods were predominant instead. One bacterial species detected in a normal adult was not related to those detected in primary biliary cirrhosis and cholecystolithiasis patients. No bacterial DNA was detected by PCR amplification in 10 liver explants of patients with primary biliary cirrhosis. CONCLUSIONS: The present results raise several possible roles of gram-positive bacteria in bile in the etiopathogenesis of primary biliary cirrhosis. However, these results could also reflect an epiphenomenon due to decreased bile flow in the patients with primary biliary cirrhosis at an advanced stage.

Adult↗

PubMed2000

Immunological similarities between primary sclerosing cholangitis and chronic sclerosing sialadenitis: report of the overlapping of these two autoimmune diseases.

Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC. In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen. We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.

Antibodies, Monoclonal↗