Biomedical subjects

Y Nakanuma

Publications and source records attributed to Y Nakanuma.

At least 73 records · Page 4Linked to original sources

PubMed1999

In situ nucleic acid detection of human telomerase in intrahepatic cholangiocarcinoma and its preneoplastic lesion.

Human telomerase, an enzyme associated with cellular immortality and tumorigenesis, is expressed by most malignant tumor cells. Human telomerase consists of human telomerase RNA (hTR) and telomerase protein components. One of the latter has been cloned and was termed telomerase-associated protein 1 (TP1). Using an in situ hybridization method, expression of hTR and TP1 mRNA was surveyed in 20 cases of intrahepatic cholangiocarcinoma (ICC) (5 of them were associated with hepatolithiasis), 5 cases of hepatolithiasis alone and 6 normal livers. Biliary dysplasia, which is suspected as a preneoplastic lesion of ICC, was found in the biliary tree in all 5 ICC cases with hepatolithiasis and in 1 of 5 cases of hepatolithiasis alone. Normal colonic mucosa was used as positive control. In 17 (85%) of 20 ICC cases, hTR and TP1 mRNA were detected in carcinoma cells. There was no correlation between histological subtype of ICC and expression of hTR and TP1 mRNA. Biliary dysplasia was also positive for both RNA. These signals were mainly located in the cytoplasm of carcinoma and dysplastic cells, especially around their nuclei. The signals were homogeneously detected in the carcinoma, while their distribution was more or less heterogeneous in the dysplastic foci. These signals were not detected in nondysplastic biliary epithelia in hepatolithiasis and normal livers. It seems likely that almost all ICC acquired telomerase activities irrespective of histological subtype and more importantly that cellular immortalization has already occurred in biliary dysplasia and this lesion is already involved in the malignant progression of ICC.

Aged↗

PubMed1999

Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation.

Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.

Adult↗

PubMed1999

Definition and pathology of primary sclerosing cholangitis.

Although primary sclerosing cholangitis (PSC) is not a common disease, it is important in the differential diagnosis of hepatobiliary tract diseases in clinical practice. A diagnosis of PSC should be made only after the exclusion of similar diseases with well known etiologies or pathogeneses. In this review, the pathology of classical PSC and its variants or related diseases is highlighted. PSC is histologically characterized by progressive periductal fibrosis with luminal stenosis or obliteration, along with the formation of a fibrous core, as well as dilatation (cholangiectasis). Its etiology is unknown. Bacterial ascending cholangitis is superimposed on its long clinical course. Such a heterogeneous distribution of biliary lesions with biliary obliteration and cholangiectasis is responsible for the radiological demonstration of biliary abnormalities, particularly the beaded appearance. Sampling variability is common in needle or wedge biopsied specimens. As a result of biliary damage, the liver shows progressive cholestatic change followed by biliary fibrosis and cirrhosis, and this hepatic progression is divisible into four stages. There are several variants of PSC or related diseases, such as localized biliary sclerosis and stenosis, sclerosing cholangitis associated with inflammatory pseudotumor, and PSC-autoimmune hepatitis overlapping syndrome. Cholelithiasis, including secondary hepatolithiasis and, to a lesser degree, biliary carcinoma and dysplasia, are also known to develop at the perihilar bile ducts as a late complication of PSC.

Biliary Tract↗

PubMed1999

Mucin-producing biliary papillomatosis associated with gastrobiliary fistula.

We report a case of mucin-producing biliary papillomatosis in a 78-year-old woman. Abdominal ultrasound (US) and computed tomography (CT) showed wall thickening and dilatation of the intrahepatic bile duct (IHBD), as well as a nodular lesion, 1.2 cm in diameter, in the left branch of the IHBD. Gastric endoscopy revealed excretion of bile-containing mucin on the anterior wall of the body of the stomach. Endoscopic ultrasonography (EUS) showed gastrobiliary fistula and discharge of mucin into the stomach. Needle biopsy of the biliary tumor revealed papillary proliferation, but no malignant cells were recognized histologically. Therefore this patient was diagnosed as having mucin-producing biliary papillomatosis forming gastrobiliary fistula. She did not present with obstructive jaundice, probably because of the fistula. She is alive, without obstructive jaundice, 16 months after the diagnosis without having had surgery. This is, to our knowledge, the first reported case of biliary papillomatosis forming gastrobiliary fistula and with the patient free of obstructive jaundice.

Aged↗

PubMed1999

A case report of gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation.

We report herein an unusual gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation in a 63-year-old Japanese male. The tumor was a pedunculated large polypoid tumor (7 x 6.5 x 3.5 cm) located in the pylorus. Histologically, it invaded to the subserosa and was composed of both adenocarcinomatous and sarcomatous components. Adenocarcinomatous foci generally showed tubular to solid patterns and occupied the parts facing the gastric lumen, while the sarcomatous components showed a generally irregular and solid arrangement. There were transitions between the sarcomatous and carcinoma elements. In addition, carcinoma cells with a cord-like or trabecular arrangement similar to that seen in endocrine carcinoma expressed chromogranin A, and were mainly observed in an intermediate area between the adenocarcinomatous and sarcomatous foci. The sarcomatous areas were mainly composed of spindle cells and occasionally contained a sarcomatous component showing rhabdomyosarcomatous differentiation. This is an interesting case to consider how the variety of cell type appeared in such a type of tumor in the stomach.

Biomarkers, Tumor↗

PubMed1999

Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma.

AIMS: The significance of molecular and genetic alterations of p53 and ras in the development and progression as well as the histological differentiation of intrahepatic cholangiocarcinoma (ICC) was evaluated. METHODS AND RESULTS: We examined immunohistochemically ras p21 protein and p53-related products (p53 protein, WAF-1 and mdm-2) in 43 cases of ICC. In addition, point mutations of ras and p53 were examined genetically in selected ICC cases by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequence analysis. Point mutation of K-ras gene codon 12 was detected in three of 14 cases and one of 15 cases by PCR-RFLP and direct sequence analysis, respectively. Immunoreactivity of ras p21 protein was not detected. Point mutation of p53 was detected in three of 15 cases. p53 protein was immunohistochemically detectable in 33 of 43 cases. Immunoreactivity of p53 was more frequent in well-differentiated and less frequent in poorly differentiated cases. Immunoreactivity of WAF-1 and mdm-2 was seen in 16 and eight of 43 cases, respectively. Both proteins were frequently detected in the cases positive for p53 protein. CONCLUSION: These results suggest that dysregulation of ras is involved in at least 20% of ICC and expression of p53 protein is more significantly involved in ICC, particularly in the well and moderately differentiated cases. While some cases of p53 expression may be explainable by point mutation of p53, there may be some epigenetic phenomena that stabilize p53 protein in ICC. That is, wild type p53 may be stabilized and then detectable by forming complexes with other molecules of p53 downstream effector genes, such as WAF-1 and mdm-2.

Adult↗

PubMed1999

Significance of CD30-positive lymphocytes in livers in primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the destruction of intrahepatic small bile ducts. It is generally believed that cellular immune mechanisms, particularly T cells, cause this bile duct damage. CD30, which is inducible on selected T cells following activation, is regarded as important for B cell hyperactivity in several autoimmune diseases. In this study, we have attempted to examine CD30-expressing lymphocytes in PBC with respect to B cell hyperactivity. METHODS: We surveyed and counted CD30+ lymphocytes in liver sections from 13 patients with PBC and 36 control livers, including chronic viral hepatitis, extrahepatic biliary obstruction and normal liver by immunohistochemical staining. RESULTS: Several CD30+ lymphocytes were localized in inflamed portal tracts and also accentuated around the bile ducts in PBC livers, but they were rarely detected in control liver sections. The numbers of CD30+ lymphocytes in PBC were significantly higher than in control groups (P<0.01). Double immunohistochemical staining revealed that these CD30+ lymphocytes expressed CD3 as well as CD4. The number of CD30+ lymphocytes, moreover, correlated with that of immunoglobulin (Ig)A-containing cells (r=0.72) in PBC, although no such correlation between CD30+ lymphocytes and IgM or IgG-containing cells was obtained. CONCLUSIONS: These findings indicate that intrahepatic CD30+ lymphocytes have a role in IgA type, B cell abnormal hyperactivity with respect to the pathogenesis of portal tract and bile duct lesions in PBC.

Chi-Square Distribution↗

PubMed1999

Case report: mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging.

A case of mucinous cholangiocarcinoma (CC), a rare histological type of CC, featuring unusual images is reported. The patient was hospitalized because of acute development of jaundice and fever. Computed tomography demonstrated multiple cystic lesions in the liver and a band-like low density area parallel to the intrahepatic portal vein, a so-called 'periportal collar'. Endoscopic cholangiography revealed a stricture of the hepatic duct with slight upstream dilatation. Cytology of the bile juice and fine-needle aspiration of the cystic lesion in the liver disclosed mucinous carcinoma. The patient died of multiorgan failure 3 weeks after admission. The autopsied liver showed that multiple mucus lakes were lined with adenocarcinoma cells and signet ring cells were floating in the mucus lakes. The cancer cells had spread along the portal tract and invaded into the hepatic parenchyma.

Adenocarcinoma, Mucinous↗

PubMed1999

Expression of MUC2, MUC5AC and MUC6 apomucins in carcinoma, dysplasia and non-dysplastic epithelia of the gallbladder.

To date, nine apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. The purpose of this study was to characterize immunohistochemically the expression of MUC2 (colonic/ intestinal type), MUC5AC (gastric surface type), and MUC6 (pyloric gland type) apomucins in 55 patients with gallbladder carcinoma (10 with in situ carcinoma, 45 with invasive carcinoma), 20 patients with gallbladder dysplasia, and 15 patients with non-dysplastic gallbladder. MUC2 was expressed mainly in 'goblet type' cells. The frequency was increased in non-dysplastic gallbladder (47%), dysplasia (75%), and in situ carcinoma (100%), and decreased in invasive carcinoma (58%). Carcinoma cells expressing MUC2, which were usually distributed at superficial areas, and well-differentiated carcinoma expressed MUC2 more extensively than moderately and poorly differentiated ones. MUC5AC was frequently expressed in gallbladder irrespective of non-dysplastic epithelia, dysplasia and carcinoma. MUC5AC was expressed also in carcinoma cells at deeply invasive sites. MUC6 was expressed frequently in pseudopyloric gland metaplasia as well as dysplasia and carcinoma. In conclusion, non-dysplastic gallbladder has a similar phenotype to gastric pyloric mucosa. Gallbladder carcinoma exhibits both intestinal and gastric surface phenotypes in the early stage of carcinogenesis, with the gastric surface phenotype dominant in invasive carcinoma.

Adult↗

PubMed1999

Expression of sialyl-Tn, Tn and T antigens in primary liver cancer.

Sialyl-Tn, Tn and T antigens are caused by aberrant or incomplete glycosylation of apomucins and are related to the aggressiveness of malignant neoplasms. Using 41 liver samples from patients with cholangiocarcinoma (including four with cirrhosis), 21 with combined hepatocellular-cholangiocellular carcinoma and 17 with hepatocellular carcinoma, the expression of sialyl-Tn, Tn and T antigens were characterized immunohistochemically and the correlation with apomucin profiles was evaluated. The prevalence of sialyl-Tn, Tn and T antigens expression was 89, 95 and 51% in cholangiocarcinoma without cirrhosis; 25, 75, and 0% in cholangiocarcinoma with cirrhosis; 29, 90, and 48% in combined hepatocellular-cholangiocellular carcinoma; and 0, 12 and 6% in hepatocellular carcinoma, respectively. Sialyl-Tn antigen was frequently expressed in cholangiocarcinoma without cirrhosis compared with cholangiocarcinoma with cirrhosis and combined hepatocellular-cholangiocellular carcinoma (P < 0.01). Although sialyl-Tn expression was associated with MUC1, MUC6 and MUC7 expression, the expression sites among them were not identical in the individual cases. These data suggest that the different expressions of sialyl-Tn antigen among cholangiocarcinoma without cirrhosis, cholangiocarcinoma with cirrhosis and combined hepatocellular-cholangiocellular carcinoma may reflect the biological features inherent to these tumors, such as the ability of invasion.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1999

An immunohistochemical study on a case of granulocyte-colony stimulating factor-producing gall-bladder carcinoma.

Primary gall-bladder carcinoma producing granulocyte-colony stimulating factor (GCSF) is extremely rare. Only four cases, histologically investigated, have been reported to date in the English literature. We report a case of a 48-year-old female with primary gall-bladder carcinoma, associating with leukocytosis (15 700/mm3) and a high level of serum GCSF (54.0 pg/mL). The tumor was, histologically, a poorly differentiated adenocarcinoma with marked interspersed neutrophils invading into the primary tumor itself and the right lobe of the liver. Tumor cells distinctly showed positive immunoreaction in the cytoplasm with anti-GCSF antibody, and in the nucleus for anti-p53 antibody. After surgery, the leukocytosis and serum level of GCSF began to decrease. These findings confirmed the present case of GCSF-producing gall-bladder carcinoma, exhibiting leukocytosis. A total of five cases, including our case, reported as a GCSF-producing gall-bladder carcinoma were clinicopathologically reviewed.

Adenocarcinoma↗

PubMed1999

Hepatic angiomyolipoma: a clinicopathologic study of 30 cases and delineation of unusual morphologic variants.

Hepatic angiomyolipoma (AML) is frequently misdiagnosed. HMB-45 is a promising immunomarker for this tumor that leads to recognition of some AMLs with unusual morphology. The purpose of this collaborative study is to better define the morphologic variations of AML. Thirty AMLs were examined, including four biopsy specimens and two fine-needle aspirates. The diagnosis was confirmed by the presence of HMB-45-positive myoid cells. Almost half the cases were originally misdiagnosed as carcinomas or sarcomas. There was marked female predominance (25:5), and the mean age was 48.7 years (range 29-68). Three patients (10%) had evidence of tuberous sclerosis and all had renal AML. According to the line of differentiation and predominance of tissue components, the tumors was subcategorized into mixed, lipomatous (> or = 70% fat), myomatous (< or = 10% fat), and angiomatous type. The mixed type was the most common (11 resected cases), comprising sheets of epithelioid muscle cells admixed with islands of adipocytes, abnormal vessels, and frequently, hematopoietic cells. Six tumors (including three from biopsy specimens) were heavily fatty and showed predominantly adipocytes with epithelioid and short spindle myoid cells webbed between fat cells. Of 10 myomatous AMLs, five tumors showed a pure sinusoidal trabecular pattern and comprised mainly epithelioid cells. Typically, mature adipocytes were absent or scanty, but fat was seen as fine droplets within cytoplasm or as occasional large globules in sinusoids. Pelioid and inflammatory pseudotumor-like patterns were identified focally. Regarding cellular features of the myoid cells, most of the epithelioid cells were either eosinophilic or clear with spiderweb cell morphology. Three AMLs showed an almost purely oncocytic appearance with scanty fat. Large pleomorphic epithelioid cells existed as small foci. Spindle cells arranged in long fascicles were uncommon. D-PAS-positive globules were common around pelioid areas. Brown pigments with staining characteristics of hemosiderin and/or melanin were noted. In conclusion, we propose HMB-45-positive myoid cells as the defining criterion of hepatic AML, which is a tumor capable of dual myomatous and lipomatous differentiation and melanogenesis. Because of its protean morphologic appearance, recognition of the various variant patterns and cell types is important for a correct diagnosis, assisted by immunohistochemical confirmation with HMB-45. Trabecular and oncocytic cell tumors appear to stand out as distinctive subtypes.

Adult↗

PubMed1999

An unusual case of epithelial-myoepithelial carcinoma of the liver.

The authors present an unusual case of an epithelial-myoepithelial carcinoma of the liver in a 67-year-old man who was admitted for resection of a gastric adenocarcinoma. At operation, a 3 x 3 cm mass in the right liver lobe was also removed. This mass consisted of duct-like structures with dual differentiation. The inner layer was composed of an epithelial lining, and the outer layer consisted of clear cells, all unrelated to the moderately well-differentiated gastric adenocarcinoma. The clear cells were positive for S-100 and alpha-smooth muscle actin, suggesting myoepithelial origin. The mass was considered to be low-grade epithelial-myoepithelial carcinoma. However, the patient had a history of an oral nodule present since childhood, resected 10 years previously. These slides were reviewed and revealed a mixture of clear cells and basal cells with squamous differentiation. In addition, there were duct-like structures with the two-layer pattern found in the liver tumor. This tumor had numerous mitotic figures and showed perineural invasion, suggesting a high grade of malignancy. These findings led to an interpretation of the oral tumor as also being epithelial-myoepithelial carcinoma, which had remained as "benign" for more than 50 years and subsequently underwent malignant transformation. During this long period, liver metastases may have occurred and remained low-grade. Alternatively, the liver and oral tumors may have arisen separately in the foregut during embryologic development, remaining low-grade until malignant transformation occurred.

Actins↗

PubMed1999

Autoimmune cholangitis and primary biliary cirrhosis--an autoimmune enigma.

AIMS/BACKGROUND: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients. METHODS: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared. RESULTS: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex. CONCLUSION: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.

Adult↗

PubMed1999

Frequent expression of mucin core protein MUC1 in non-neoplastic gallbladder mucosa from patients with pancreaticobiliary maljunction.

BACKGROUND: Gallbladder carcinoma is known to develop frequently in patients with pancreaticobiliary maljunction, though the causal relationship remains speculative. METHODS: Histopathologic changes, expression of mucin core protein MUC1 and MUC2, and cell proliferative activities in the gallbladder mucosa from 27 patients with panceaticobiliary maljunction and 21 control gallbladders were examined. Three cases of pancreaticobiliary maljunction were associated with gallbladder carcinoma. RESULTS: The lining epithelia of the non-neoplastic gallbladder mucosa of pancreaticobiliary maljunction showed frequently papillary hyperplasia and higher proliferative activities, when compared to the control. In 3 cases with carcinoma, MUC1 was expressed on the luminal border and in the cytoplasm of carcinoma cells, particularly in de-differentiated and invasive areas. MUC1 was variably expressed on the luminal surface of the lining epithelia of non-neoplastic gallbladder mucosa in babies, children, youths and adults with pancreaticobiliary maljunction. However, such expression was focally seen in 2 of the 21 control cases (p<0.01). MUC2 was scattered in the hyperplastic and carcinomatous epithelial cells appearing as goblet cells in pancreaticobiliary maljunction and control groups. CONCLUSIONS: This study suggests that persistent MUC1 expression and increased cell proliferative activities of non-neoplastic gallbladder epithelium of the patients with pancreaticobiliary maljunction after birth reflect an altered phenotype of epithelial cells and these abnormalities may be related to carcinogenesis in such patients.

Adult↗

PubMed1999

Expression of nerve growth factor in hepatolithiasis.

AIMS/BACKGROUND: Nerve growth factor (NGF) has recently been shown to influence the survival and function of non-neuronal inflammatory cells, possibly through its activity as a colony-stimulating factor. It may also play an important role in acute inflammation and tissue repair. However, no prior report has focused on NGF in chronic inflammatory diseases of the gastrointestinal and biliary tracts. The aim of this study was to examine the expression of NGF in hepatolithiasis. METHODS: Twenty-six liver specimens resected from 22 patients with intrahepatic calcium bilirubinate stones and from 4 patients with intrahepatic cholesterol stones were examined immunohistochemically. RESULTS: The 22 patients with calcium bilirubinate stones demonstrated NGF immunoreactivity associated with surrounding inflammatory cells that was localized to the epithelia of proliferative peribiliary glands in the ductal wall. However, neither the surface lining of the bile duct nor hepatocytes expressed detectable NGF immunoreactivity. In the cholesterol stones cases in contrast, peribiliary glandular elements and inflammatory cell infiltration were less extensive than those observed in cases of calcium bilirubinate stones, and NGF immunoreactivity was not noted. CONCLUSIONS: These observations suggest that proliferative peribiliary glands express NGF protein in chronic proliferative cholangitis. This is characteristic of intrahepatic calcium bilirubinate stones.

Adult↗

PubMed1999

Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium.

OBJECTIVE: The purpose of this study is to evaluate the correlation between the intranodular blood supply revealed by CT during intraarterial injection of contrast medium, mainly using helical CT, and the grade of malignancy of hepatocellular nodules associated with liver cirrhosis as classified by the International Working Party of the World Congress of Gastroenterology. SUBJECTS AND METHODS: We studied 201 histologically proven nodules (101 resected and 100 biopsied nodules), including 47 low-grade dysplastic nodules (low-DNs), 56 high-grade dysplastic nodules (high-DNs), 24 well-differentiated hepatocellular carcinomas (wd-HCCs), and 74 moderately or poorly differentiated HCCs (mp-HCCs), in 139 cirrhotic patients. Findings on CT during arterial portography (n = 201) and CT during hepatic arteriography (n = 74) were reviewed and compared with the histologic diagnosis. RESULTS: CT findings were classified into four types relative to the surrounding liver: type A (isodense), type B (slightly hypodense), type C (partially hypodense), and type D (markedly hypodense) on CT during arterial portography and type I (isodense), type II (hypodense), type III (partially hyperdense), and type IV (hyperdense) on CT during hepatic arteriography. On CT during arterial portography, the distributions of each type were low-DN (n = 47 [A, n = 36; B, n = 8; C, n = 3]), high-DN (n = 56 [A, n = 18; B, n = 20; C, n = 10; D, n = 8]), wd-HCC (n = 24; [B, n = 4; C, n = 13; D, n = 7]), and mp-HCC (n = 74 [D, n = 74]). On CT during hepatic arteriography, the distributions were low-DN (n = 26 [I, n = 18; II, n = 7; III, n = 1]), high-DN (n = 19 [I, n = 6; II, n = 7; III, n = 4; IV, n = 2]), wd-HCC (n = 15 [I, n = 1; III, n = 8; IV, n = 6]), and mp-HCC (n = 14 [IV, n = 14]). We found a statistically significant correlation between the four types and the grade of malignancy of these nodules. CONCLUSION: Findings on CT during arterial portography and CT during hepatic arteriography correlated positively with histologic grading when overlap in appearance between dysplastic nodules and HCCs occurred. The concept revealed in this study can apply to diagnoses made on the basis of Doppler sonography, dynamic CT, and MR imaging.

Aged↗

PubMed1998

Monoclonal antibodies to mitochondrial E2 components define autoepitopes in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial Abs (AMA). The autoantigens recognized by AMA are the E2 components of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxoacid dehydrogenase complex E (BCOADC-E2), and the 2-oxoglutarate dehydrogenase complex E (OGDC-E2). Previous studies using murine monoclonal and human combinatorial Abs to PDC-E2 have demonstrated an intense linear staining pattern in the apical region of biliary epithelial cells (BEC) in PBC but not control liver. We therefore examined whether mAbs to the other mitochondrial autoantigens BCOADC-E2 and OGDC-E2 demonstrated disease-specific patterns of reactivity. Using an expressed recombinant "trihybrid" protein containing the lipoyl domains of PDC-E2, OGDC-E2, and BCOADC-E2, we immunized BALB/c mice to produce 35 mAbs specific for one or more of the above mitochondrial autoantigens. Seven of these mAbs uniquely stained the apical region of BEC in PBC. Of these seven, one was reactive to PDC-E2, two recognized BCOADC-E2, three were reactive to OGDC-E2, and one recognized all three Ags. Our current data demonstrate that, similar to our previous studies regarding PDC-E2, mAbs to BCOADC-E2 and OGDC-E2, or a molecule that cross-reacts with the inner lipoyl domain of all three enzymes, also show a uniquely intense staining pattern in the apical region of BEC in patients with PBC when compared with diseased controls. The abundance of such disease-specific determinants in the target cells of PBC raises interesting possibilities regarding the role of these autoantigens in the pathogenesis of this disease.

Animals↗