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Y Nakanuma

Publications and source records attributed to Y Nakanuma.

At least 91 records · Page 5Linked to original sources
PubMed1998

Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer.

BACKGROUND AND OBJECTIVES: The most reliable method for the diagnosis of peritoneal dissemination of gastric cancer at the present time is cytological examination of ascitic fluid, which is unavailable to patients without ascites or may be inadequate for those with ascites containing few cancer cells. It has been reported recently that human gastric cancer immunoreacted with a monoclonal antibody against pancreatic trypsinogen. We therefore examined the expression of trypsinogen as a new marker for the early diagnosis of peritoneal dissemination of gastric cancer. METHODS: Pancreatic trypsinogen protein was immunohistochemically stained with a three-step indirect immunoperoxidase method and cationic trypsinogen (trypsinogen-1) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in gastric cancer. Twenty-nine of 30 primary tumors (97%) and all 12 tumors (100%) of the peritoneal seedings immunohistochemically reacted with trypsinogen. Preliminary study for early diagnosis of peritoneal dissemination was carried out for eight more recent patients who showed positive immunoreactivity to trypsinogen protein and expressed trypsinogen- mRNA in the primary tumor. The expression of trypsinogen-1 mRNA was detected by using peritoneal lavage fluid preoperatively collected in these patients. RESULTS: All three patients in whom peritoneal dissemination was diagnosed at the time of their operation(s) expressed trypsinogen-1 mRNA. One patient, who did not show peritoneal dissemination at the operation but was positive for trypsinogen-1 mRNA detection, later died of the recurrence of peritoneal dissemination. CONCLUSIONS: These results indicated that trypsinogen protein and trypsinogen-1 mRNA frequently expressed in peritoneal dissemination as well as primary tumors in gastric cancer and detection of trypsinogen-1 mRNA expression was a useful method for early diagnosis in peritoneal dissemination of gastric cancer.

Adenocarcinoma↗
PubMed1998

Increased MUC6 apomucin expression is a characteristic of reactive biliary epithelium in chronic viral hepatitis.

The significance of bile ductular proliferation in the progression of various hepatobiliary diseases remains unclear. Increased expression of MUC6 apomucin, a major gastric mucin, has previously been noticed in proliferating bile ductules in chronic viral hepatitis. The purpose of the present study was to characterize MUC6 apomucin and mRNA expression in 35 histologically 'normal livers', 47 livers with chronic viral hepatitis, 28 with primary biliary cirrhosis, and seven with extrahepatic biliary obstruction. MUC6 protein was expressed focally in cytoplasm and/or on the luminal surface of septal and interlobular bile ducts in normal and diseased livers. Bile ductules in normal livers rarely expressed MUC6 protein. The MUC6 expression intensified and spread in proliferating bile ductules and small bile ducts in chronic viral hepatitis and to a lesser degree in other diseases. In the former, the extent and degree of MUC6 expression paralleled the degree of active necroinflammation. MUC6 mRNA expression resembled MUC6 protein expression in proliferating bile ductules and intralobular small biliary cells, suggesting increased transcription and synthesis of MUC6. In conclusion, proliferating bile ductular cells express MUC6 apomucin in diseased liver, especially in chronic viral hepatitis with active necroinflammation. This secreted mucin may act as a cytoprotective agent and represent a phenotype of reactive biliary epithelium in chronic viral hepatitis.

Bile Ducts, Intrahepatic↗
PubMed1998

Expression of co-stimulatory factor B7-2 on the intrahepatic bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis: an immunohistochemical study.

Co-stimulatory factors B7-1 (CD80) and B7-2 (CD86) and their ligands, including CD28, are important for the efficient presentation and persistence of an antigen-specific immune reaction. Hitherto, there has been a paucity of data on the roles of such co-stimulatory factors in immune-mediated biliary diseases. In this investigation, the hepatic immunohistochemical expression of B7-1 and B7-2 has been studied, with emphasis on intrahepatic biliary epithelia, using wedge biopsies from 22 patients with primary biliary cirrhosis (PBC), seven with primary sclerosing cholagitis (PSC), and, as controls, eight cases of extrahepatic biliary obstruction, eight of chronic viral hepatitis C, and three histologically normal livers. In 10/22 (45 per cent) patients with PBC and 3/7 (43 per cent) patients with PSC, B7-2, but not B7-1, was expressed on the epithelial cells of small intrahepatic bile ducts and bile ductules. This expression was manifest as diffuse but variable cytoplasmic staining. Such B7-2-positive bile ducts were not seen in controls. Positive staining was found only in the early stage of PBC and PSC. In PBC and PSC, almost all lymphocytes in the portal tracts, including those around the damaged bile ducts, were positive for CD28, a ligand of B7-2. These results suggest that B7-2 expression on biliary epithelial cells is involved in antigen presentation and perhaps in bile duct destruction in PSC and PBC.

Antigens, CD↗
PubMed1998

Expression of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from that in normal liver and extrahepatic biliary obstruction.

Mucin plays an important role in the development of hepatoliths, which are formed within the intrahepatic large bile ducts. To date, eight apomucins, components of mucin, have been identified. The purpose of this study is to characterize the expression of MUC1, MUC2, MUC3, MUC5, and MUC6 apomucins at both the protein and messenger RNA (mRNA) levels in the intrahepatic large bile ducts and peribiliary glands in 36 livers from patients with hepatolithiasis, in 25 livers from the patients with extrahepatic biliary obstruction, and in 23 histologically-normal livers. MUC3 and MUC6 were constantly and focally expressed, respectively, in the biliary epithelial cells in the intrahepatic large bile ducts in normal livers, extrahepatic biliary obstruction, and, also, hepatolithiasis. In hepatolithiasis, MUC1, MUC2, and MUC5 apomucins were also focally expressed in 33%, 64%, and 89%, respectively, of the large intrahepatic bile ducts examined, whereas such expression was infrequent in normal livers and in extrahepatic biliary obstruction. The markedly proliferated intramural and extramural peribiliary glands in hepatolithiasis frequently expressed MUC3 and MUC6 apomucins and focally expressed MUC2 and MUC5 apomucins. All of the apomucins mRNA expression, except that of MUC1, resembled each protein expression. In conclusion, the characteristics of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from those in normal livers and extrahepatic biliary obstructrion. Increased expression of gel-forming mucins, such as MUC5 and MUC2, could be involved in the formation and development of hepatolithiasis.

Bile Ducts, Intrahepatic↗
PubMed1998

aly/aly mice: a unique model of biliary disease.

An autosomal recessive murine mutation, coined "aly/aly" or "alymphoplasia," was recently reported. Homozygotes for aly are defective in both humoral and cell-mediated immune function and have diffuse lymphoid cell infiltration of various tissues, particularly around the conduit ducts of the pancreas and salivary glands. In pilot studies in our laboratories, aly/aly mice were found to have peculiar biliary tract lesions, which were analyzed histologically and immunohistochemically in the present study. The livers of aly/aly mice older than 8 weeks consistently showed a variable lymphoid cell infiltration with lymph follicle formation in portal tracts; intrahepatic biliary epithelial cells showed various types of damage including pseudopyloric gland metaplasia and proliferative changes. In addition, the extrahepatic bile duct and intrahepatic large bile duct were found to contain an acidophilic substance in their epithelial cytoplasm. In the lumen and occasionally in the cytoplasm of these bile ducts, acidophilic crystals were also seen. Ultrastructurally, the intracytoplasmic acidophilic substances consisted of membrane-bound intracytoplasmic inclusions with homogeneous electron density, likely derived from rough endoplasmic reticulum (ER). Immunohistochemically, the cytoplasmic acidophilic substances were simultaneously positive for cystatin C, gastrin, serotonin, and somatostatin. In contrast, the acidophilic crystals did not react with any of these antibodies. These findings suggest that the intracytoplasmic acidophilic substances may contain a precursor of the peptide hormones, possibly because of defective secretion or intracellular transport. We believe that the aly/aly mouse is a useful model for the analysis of biliary metabolic events, and for studies of the interaction of the immune system and biliary destruction.

Animals↗
PubMed1998

Increased CD1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis.

Cluster of differentiation 1 (CD1) is a family of four distinct nonpolymorphic major histocompatibility complex class I-like molecules that can present microbial nonpeptide lipid antigens to T cells. Among the CD1 gene family, CD1d is found in a wide range of tissues including the intestine and liver, and has been proposed to play an important role in mucosal immunity. Primary biliary cirrhosis (PBC) is an immune-mediated liver disease involving the intrahepatic small bile ducts, which also belong to the mucosal immune system. In this study, we studied the expression of CD1d in patients with PBC and compared the data with those of patients with hepatic sarcoidosis, primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), and normal liver as controls. CD1d was found to be expressed in hepatocytes in all cases examined, and in epithelioid granuloma cells in 19 of 22 PBC livers and in 4 of 4 livers with hepatic sarcoidosis. In addition, CD1d was focally expressed on epithelial cells of the small bile ducts in approximately 50% of the PBC patients but in no controls. Such bile duct epithelial staining of CD1d was seen in early-stage PBC and virtually absent in late-stage PBC. Moreover, there was no evidence of expression of CD1d in large bile duct epithelial cells of PBC. The CD1d on biliary epithelial cells in PBC may be involved in the antigen presentation of microbial lipid antigen(s) to surrounding T cells. Alternatively, modified endogenous lipidic compounds may share analogy with bacterial lipid antigens and explain CD1d expression, a possible epiphenomenon rather than a proof of bacterial involvement.

Adult↗
PubMed1998

Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study.

There is evidence that mast cells are involved in a number of pathophysiological processes. The significance of mast cells in hepatic fibrosis was examined in 28 patients with histologically normal livers, 34 with acute liver diseases, 51 with chronic liver diseases, and 59 with cholestatic biliary diseases, using immunostaining of the mast cell-specific proteinase, tryptase. Mast cells that were positive for tryptase and for chymase were significantly increased in frequency in fibrotic portal tracts and fibrous septa, particularly in cholestatic/biliary diseases. Mast cells were also increased in frequency around the fibrotic septal and intrahepatic large bile ducts and peribiliary glands of biliary diseases. However, they were less common or even rare in the sclerotic bile ducts and in scarred portal or septal fibrosis. More than half of these more numerous mast cells were positive for histamine, and some were also positive for basic fibroblast growth factor. These two substances were detectable by immunoelectron microscopic in the cytoplasmic granules of mast cells. In contrast, mast cell numbers were not significantly increased in acute viral or drug-induced hepatitis, or in zones 2 and 3 of the hepatic acinus with respect to pericellular and perivenular fibrosis in chronic liver diseases. These findings suggest that mast cells increase in number in cholestatic/biliary diseases, and to a lesser degree in chronic liver diseases, and are involved in the active fibrous enlargement of portal tract and fibrous septa formation and also in the fibrosis of the intrahepatic bile ducts as they display fibrosis-promoting factors such as tryptase, fibroblast growth factor and histamine.

Acute Disease↗
PubMed1998

Histological features predicting malignant transformation of nonmalignant hepatocellular nodules: a prospective study.

BACKGROUND & AIMS: Recent advances in imaging modalities allow the identification of borderline hepatocellular nodules that have the potential for malignant transformation. The aim of this study was to elucidate histological predictive features of borderline nodules by needle biopsy for the evolution to hepatocellular carcinoma (HCC). METHODS: Thirty-four hepatocellular nodules diagnosed by needle biopsy were followed up for more than 6 months. Several histological parameters of these nodules that were related to malignant transformation were evaluated. RESULTS: During the follow-up periods (median, 35 months), 5 of 34 nodules evolved to HCC during a follow-up of 6-15 months. Significant prognostic features of malignant transformation were an increased ratio of nuclear density of >1.5, clear cell change, small cell dysplasia, and fatty change of the hepatocytes. In multivariate analysis, an increased ratio of nuclear density of >1.5 and clear cell change were independent. CONCLUSIONS: A nodule with an increased ratio of nuclear density, clear cell change, small cell dysplasia, and fatty change should be recognized to be a high risk for evolution to HCC. Particularly, the former two were independent prognostic factors for malignant transformation.

Biopsy, Needle↗
PubMed1998

Immunohistochemical demonstration of MET overexpression in human intrahepatic cholangiocarcinoma and in hepatolithiasis.

Expression of MET, the c-met-encoded receptor for hepatocyte growth factor, has not been investigated in proliferative biliary diseases of human liver, including hepatolithiasis and cholangiocarcinoma. Comparatively, we analyzed by immunohistochemistry the expression of MET in normal adult human livers (n = 20), normal postnatal preadult livers (n = 21), fetal livers (n = 36), hepatolithiatic livers (n = 32), and intrahepatic cholangiocarcinomas (n = 26). In normal adult livers, obvious MET immunoreactivity was not found in any cell types. In fetal liver, MET was weakly expressed in primitive biliary cells (ductal plate and immature bile ducts) and immature hepatocytes during 8 to 30 gestational weeks but was essentially negative thereafter. In hepatolithiasis, a condition of risk for cholangiocarcinoma development, MET was overexpressed in proliferated biliary cells in 26 of 32 cases (81%). In this nonneoplastic proliferative biliary condition, MET immunoreactivity was observed to be most prominent in the hyperplastic septal and large bile ducts of liver, and in the proliferated peribiliary glands associated with intrahepatic large bile ducts. In intrahepatic cholangiocarcinoma, MET overexpression in neoplastic biliary epithelium was observed in 15 of 26 cases (58%) and correlated with the degree of tumor differentiation, being highest in well-differentiated tumors and relatively low in poorly differentiated tumors. These data show for the first time that overexpression of MET is a common feature of hyperplastic and neoplastic biliary epithelial cells in human liver and suggest that MET/hepatocyte growth factor may be playing an important role in human biliary hyperplasia and in cholangiocarcinogenesis in vivo.

Adult↗
PubMed1998

Intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis: report of an autopsy case.

We report an autopsy case of a 60-year-old woman who had congenital hepatic fibrosis with intrahepatic cholangiocarcinoma. A white nodular lesion with a surrounding vague gray area was detected in the right lobe of the liver. Microscopically, most of the nodular lesion was a poorly-differentiated adenocarcinoma. In the surrounding gray area, small bile ducts and bile ductules showed prominent epithelial overgrowth, some of which was composed of dysplasia and well-differentiated adenocarcinoma. The background liver showed the characteristic features of congenital hepatic fibrosis. Immunohistochemically, biliary oncofetal markers (mucin core protein 1 and carcinoembryonic antigen) were more frequently and extensively expressed in poorly-differentiated than well-differentiated adenocarcinoma. This is the 4th reported case of intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis and suggests that malignant transformation via dysplasia occurs in the abnormal intrahepatic biliary tree of older congenital hepatic fibrosis patients.

Autopsy↗
PubMed1998

Relationship between interleukin-6 and proliferation and differentiation in cholangiocarcinoma.

AIMS: Interleukin-6 (IL-6) has been implicated as a mediator of growth control in several human neoplasms. The significance of IL-6 expression in human cholangiocarcinoma was examined in this study. METHODS AND RESULTS: IL-6 expression was examined in 43 surgically resected cholangiocarcinomas and a cholangiocarcinoma cell line CCKS1, derived from abdominal metastasis of moderately differentiated adenocarcinoma, by immunohistochemical and in-situ hybridization techniques. In non-neoplastic bile ducts, IL-6 was constitutively but weakly expressed. In surgical cases of cholangiocarcinoma, IL-6 was frequently and strongly expressed in the cytoplasm of well-differentiated cholangiocarcinoma, while its expression was decreased, and less intense or absent in moderately and poorly differentiated areas, respectively. IL-6 mRNA was detected in the cytoplasm of carcinoma cells of two cases of cholangiocarcinomas positive for IL-6. IL-6 was detected in hepatic bile from two cholangiocarcinoma cases studied. The proliferation antigen Ki67 was found to be more frequently expressed in IL-6 negative carcinoma cells than in IL-6 positive carcinoma cells (P < 0.01). In cultured carcinoma cells line CCKS1, IL-6, IL-6 mRNA and IL-6 receptor alpha chain were detected in the cytoplasm of carcinoma cells, suggesting an autocrine effect of IL-6 on carcinoma cells. CONCLUSION: IL-6 expression is inversely related to cell proliferation and positively related to differentiation in cholangiocarcinoma.

Aged↗
PubMed1998

Epithelioid cell granulomas in chronic hepatitis C: immunohistochemical character and histological marker of favourable response to interferon-alpha therapy.

AIMS: The clinicopathological significance of intrahepatic epithelioid cell granulomas in chronic hepatitis C was determined. METHOD AND RESULTS: Granulomatous lesions were surveyed in 542 liver biopsy specimens and were immunohistochemically examined. We also tested whether this lesion is a marker of response to interferon-alpha therapy in chronic hepatitis C. Granulomatous lesions in hepatic lobules and/or portal tracts were identified in 11/542 (2%) cases with chronic hepatitis C. Granulomas were positive for HLA-DR and beta 2-microglobulin, and were surrounded by T-cells. Among them, three chronic hepatitis C cases showed portal granulomas with mild biliary epithelial damage. Bile ducts showing mild epithelial damage in chronic hepatitis C were positive for beta 2-microglobulin, but negative for HLA-DR, while both antigens were frequently expressed in damaged bile ducts in primary biliary cirrhosis (PBC). All five cases of chronic hepatitis C with granulomas who had interferon-alpha therapy and were followed up and were found to have responded well. CONCLUSION: Granulomas showed the same immunohistochemical phenotypes, though the expression of HLA-DR on bile ducts in PBC but not in chronic hepatitis C suggests a different pathogenesis. Granulomas may predict a favourable response to interferon-alpha therapy in chronic hepatitis C.

Adult↗
PubMed1998

Cholangiocarcinomas arising in cirrhosis and combined hepatocellular-cholangiocellular carcinomas share apomucin profiles.

Cholangiocarcinomas occasionally arise in the nonbiliary cirrhotic liver, but their pathobiologic features remain unsettled. To characterize such cholangiocarcinomas, we examined immunohistochemically the expression of MUC3, MUC5AC, MUC6, and MUC7 apomucins in hepatic tissue specimens from 4 patients with cholangiocarcinoma and viral cirrhosis, 24 patients with cholangiocarcinoma without cirrhosis, and 16 patients with combined hepatocellular-cholangiocellular carcinoma. The cholangiocarcinomas associated with cirrhosis and the cholangiocarcinoma elements of combined hepatocellular-cholangiocellular carcinoma rarely expressed MUC3 and MUC5AC, but the cholangiocarcinomas not associated with cirrhosis frequently expressed these apomucins. MUC6 apomucin was widely expressed in cholangiocarcinomas, irrespective of the association with cirrhosis and also in the cholangiocarcinoma elements of the combined hepatocellular-cholangiocellular carcinomas. MUC7 apomucin was expressed frequently in cholangiocarcinomas associated with cirrhosis and combined hepatocellular-cholangiocellular carcinomas and infrequently in cholangiocarcinomas without cirrhosis, particularly those arising at the hepatic hilus. The similarity of the apomucin profiles between cholangiocarcinomas associated with cirrhosis and the cholangiocarcinoma elements of combined hepatocellular-cholangiocellular carcinoma suggests a similar or common histogenesis and that cholangiocarcinoma associated with cirrhosis might be derived from the combined type.

Antigens, Neoplasm↗
PubMed1998

Diffuse biliary tract involvement mimicking primary sclerosing cholangitis in an experimental model of chronic graft-versus-host disease in mice.

Experimental graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed by injecting spleen and bone marrow cells (9:1) of congenic B10.D2 mice into sublethally irradiated BALB/c mice, and the histologic features of the liver were studied for up to 14 months after transplantation. Both intrahepatic and extrahepatic bile ducts were severely involved in the GVHD process and showed features of non-suppurative cholangitis. Inflammatory cells, mainly lymphocytes, abutted the bile ducts and infiltrated into the duct epithelial layer together with a variety of degenerative changes in the epithelial cells. The peak inflammatory activity occurred about 2-3 weeks after transplantation. Thereafter, the inflammatory cell infiltration around the bile ducts and in the bile duct epithelial layer gradually became reduced in severity, although the infiltration persisted during the entire 14 month observation period. Periductal and duct wall fibroplasia began about 1 week after transplantation and gradually progressed. After 2-3 months post-transplantation, distinct ductal and periductal fibrosis of both intrahepatic and extrahepatic bile ducts was observed. This histologic feature resembled that of primary sclerosing cholangitis (PSC). These results suggest that PSC lesions might develop as a result of chronic cellular immunologic mechanisms in GVHD across minor histocompatibility barriers.

Animals↗
PubMed1998

Lipomatous pseudohypertrophy of the pancreas in a patient with cirrhosis due to chronic hepatitis B.

Lipomatous pseudohypertrophy of the pancreas was found at autopsy in a 52-year-old Japanese woman with cirrhosis due to chronic hepatitis B. Clinically, there were no clear symptoms of pancreatic insufficiency during the entire course. Marked atrophy and fat deposition of the pancreas had already been detected by computed tomography (CT) at least 6 years before her death. She died of hepatic failure due to decompensated cirrhosis. Autopsy revealed uniform enlargement of the pancreas due to massive fat replacement (lipomatous pseudohypertrophy): the exocrine glandular elements showed marked atrophy and loss, while the islets of Langerhans were preserved. Although the etiology and pathogenesis of lipomatous pseudohypertrophy is still unclear, this case suggests that this condition is causally related to chronic hepatitis B or other chronic advanced hepatic lesions.

Adipose Tissue↗
PubMed1998

A case of progressive multiple focal nodular hyperplasia with alteration of imaging studies.

Focal nodular hyperplasia (FNH) of the liver is a lesion characterized by a well circumscribed region of hyperplastic liver tissue with stellate fibrosis. The pathogenesis of the lesion is unknown but various authors consider that FNH may be a response to a preexisting vascular abnormality. We experienced a case of progressive multiple FNH, in which the hemodynamic change as shown by imaging modalities, may support this hypothesis. The patient, a 38-yr-old woman, was found by chance to have multiple portal venous shunts and multiple FNH in both lobes of her liver. Because of their benign characteristics, we followed the nodules periodically without any special treatment. After about 4 yr, the nodules increased both in size and number. In addition, digital subtraction angiography showed that the diameter of the artery had become larger. The hemodynamic change revealed by imaging studies in this case supports the hypothesis that one of the pathogens of FNH is a secondary hepatocellular response to arterial hyperperfusion caused by some vascular malformations.

Adult↗
PubMed1998

Isolation, culture and characterization of biliary epithelial cells from different anatomical levels of the intrahepatic and extrahepatic biliary tree from a mouse.

We developed methods to isolate biliary epithelial cells (BECs) from the gallbladder (GB), common bile duct (CBD), intrahepatic large bile duct (ILBD) and small bile duct (ISBD) of a mouse, simultaneously. ILBD and ISBD were cut from the biliary tree after collagenase perfusion of the liver. BECs from all of these biliary segments were cultured as explants on collagen gel. BECs spread from the explants and formed cellular sheets. Areas of these sheets composed entirely of BECs were cut and placed on other gels as subculture, and this continued for 10 passages. Primary and passage cultured BECs on gel were composed of a monolayer of epithelial cells. Passaged cultured BECs in gel formed a spherical cyst lined by a single epithelial layer. Ultrastructurally, microvilli were dense on the luminal surface, and junctional complex and interdigitation was identifiable on the lateral surfaces. These features were similar in both primary and passaged cultured BECs, irrespective of their anatomical origin. Major histocompatibility complex antigens and intercellular adhesion molecule-1 were induced on the basolateral cell membranes of primary and passaged cultured BECs, by interferon-gamma. Although several phenotypic, structural and probable biological features of BECs inherent to each anatomical level may be lost after culture on gel, a combination of this method, several immunological modifications in experimental animals, and addition of immunologically active substances to the culture medium will make the immunopathologic analysis of biliary diseases possible.

Animals↗