Biomedical subjects

T Terada

Publications and source records attributed to T Terada.

At least 127 records · Page 7Linked to original sources

PubMed1999

Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components.

Integrins play an important role in tumor dissemination. The purpose of this study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix components. Activated lansoprazole (AG-2000) was used as the SH-reactive reagent because this compound is known to react with SH groups but does not permeate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cells to matrix was examined, using both an in vitro adhesion assay and an in vivo nude mouse xenograft model of peritoneal implantation. In the in vitro adhesion assay, a 60-min exposure of AsPC-1 cells to AG-2000 resulted in a dose-dependent inhibition of AsPC-1 cell adhesion to laminin, fibronectin and type IV collagen, although AG-2000 did not affect the viability of AsPC-1 cells by MTT assay. In the in vivo assessment of AsPC-1 cell implantation, the AsPC-1 cells were initially preincubated with AG-2000 for 60 min to ensure adequate exposure of the AsPC-1 cells to AG-2000 before intraperitoneal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short exposure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracellular matrix components.

Animals↗

PubMed1999

[Caesarean section in a patient with a history of HELLP syndrome].

A 36-year-old woman underwent emergency caesarean section following the diagnosis of HELLP syndrome. Four years earlier, after having undergone the same procedure for HELLP syndrome, she had experienced hypovolemic shock, renal failure, and disseminated intravascular coagulopathy during the postoperative period. This time, the patient showed bleeding, elevation of liver enzymes (ALT, AST, LDH) and a reduction of antithrombin III activity in the 36th week of pregnancy. Anesthesia was induced by thiamylal 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and after delivery maintained by oxygen-nitrous oxide-isoflurane, and all procedures were performed without any incident. No major complications such as intraperitoneal bleeding, renal failure, or disseminated intravascular coagulopathy occurred during the postoperative period. It is suggested that caesarean section should be carried out as soon as possible after the diagnosis of HELLP syndrome is confirmed.

Adult↗

PubMed1999

Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2.

Peptide transporters (PEPT1 and PEPT2) in epithelia play an important role in the absorption of small peptides and peptide-like drugs. Recently, it was demonstrated that various nonpeptidic compounds can be transported by these transporters. In the present study, we focused on the L-amino acid ester compounds and examined the mechanisms of their interaction with rat PEPTs (rPEPTs) using stable transfectants. Valacyclovir, the L-valyl ester prodrug of the antiherpetic agent acyclovir, competitively inhibited [(14)C]glycylsarcosine uptake in the rPEPT1- or rPEPT2-expressing cells. Dixon plot analyses showed that the inhibition constant (K(i)) values of valacyclovir were 2.7 and 0.22 mM for rPEPT1 and rPEPT2, respectively, suggesting that rPEPT2 had higher affinity for this agent. Various L-valine alkyl esters significantly inhibited [(14)C]glycylsarcosine uptake. L-Valine methyl ester (Val-OMe) competitively inhibited [(14)C]glycylsarcosine uptake with K(i) values of 3.6 and 0.83 mM for rPEPT1 and rPEPT2, respectively, indicating that Val-OMe is also a high-affinity substrate for rPEPT2. Val-OMe had a trans-stimulation effect on [(14)C]glycylsarcosine efflux from both transfectants, suggesting the translocation of L-valine methyl ester via rPEPTs. Val-OMe showed the most potent inhibitory effect among the several L-amino acid methyl esters examined. We conclude that Val-OMe, as well as valacyclovir, could be recognized and transported by rPEPT1 and rPEPT2 and that these L-valyl esters showed higher affinity for rPEPT2 as do most substrates of these transporters. Our results suggest that L-valine is a desirable L-amino acid for the esterification of poorly permeable drugs to enhance their oral bioavailability targeting intestinal PEPT1.

Acyclovir↗

PubMed1999

[Treatment policy for colon cancer liver metastases].

Hepatectomy provides the highest rates of cure among the methods for treating colon cancer liver metastases, but it cannot be performed in many cases. Hepatectomy is the treatment of choice for colon cancer liver metastases in our department, but we conduct transcatheter arterial embolization alone or in combination with MCT on patients in whom hepatectomy cannot be performed or those with residual tumor following hepatectomy. Transcatheter arterial embolization is conducted on patients shown to have tumor vessels, following a single intra-arterial shot of an anticancer drug. MCT is performed under general anesthetic percutaneously or by abdominal section in patients who have not responded well to transcatheter arterial embolization, in order to improve the effectiveness of treatment on the tumor overall. We consider the combination of transcatheter arterial embolization and MCT to be an effective treatment for patients with a colon cancer liver metastasis who present with tumor vessels.

Aged↗

PubMed1999

[Dural arteriovenous fistula at the cranio-cervical junction presenting transient ischemic attack: a case report].

A 58-year-old male was admitted to our hospital because of repeated transient ischemic attack of right hemiparesis and speech disturbance. A CT scan did not demonstrate any remarkable findings. No significant cerebral arterial stenosis or occlusion was found on angiography. However, dural arteriovenous fistula fed by the radiculo-meningeal artery was found at the cranio-cervical junction on left vertebral angiography. The shunt flow from the arteriovenous fistula drained into the superior petrosal sinus and sigmoid sinus in a retrograde fashion. On the angiographic findings when his transient ischemic attack (TIA) had disappeared, the venous drainage had returned to its normal fashion. Venous hypertension around the brain stem was supposed to have caused the transient ischemic attack in this case. We performed coagulation of the draining vein and fistula surgically. After surgery, the patient's TIA completely disappeared. We report the first case of dural arteriovenous fistula at the cranio-cervical junction presenting transient ischemic attack.

Aged↗

PubMed1999

Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver.

Human liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (DD) is involved in the metabolism of steroid hormones and polycyclic aromatic hydrocarbons, and is also responsible for the reduction of ketone-containing drugs. To account for the interindividual difference in the activity, we isolated and characterized clones for the human liver enzymes. The sequence of the cDNA clone coding for the variant differed from that coding for the wild-type DD by two nucleotides (substitutions of C with G at positions 434 and 931) which caused two amino acid replacements, Ser145 to Cys (S145C) and Leu311 to Val (L311V). The heterologous expression of the variant mRNA was confirmed in four of 31 liver samples from Japanese by an allele-specific polymerase chain reaction. The effects of the mutations on the catalytic properties were examined with the recombinant enzymes expressed in Escherichia coli. The introduction of S145C/L311V double mutations resulted in three- to five-fold decreased activities for xenobiotic and steroidal substrates, whereas no significant change was observed by an introduction of the S145C mutation alone. The results substantiate the existence of polymorphic forms for human liver DD, and also suggest the importance of the residue at position 311 for substrate binding to the enzyme.

Base Sequence↗

PubMed1998

The C-terminal domain of p53 catalyzes DNA-renaturation and strand exchange toward annealing between intact ssDNAs and toward eliminating damaged ssDNA from duplex formation through preferential recognition of damaged DNA by a duocarmycin.

The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-9459, 1995). We found that DU-86, a duocarmycin derivative which alkylates DNA, bound ssDNA and enhanced the DNA binding activity of the p53 C-terminus. DU-86 weakened p53-mediated catalysis of complementary ssDNA renaturation. p53 C-terminus catalyzed DNA strand transfer toward annealing between intact ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a direct role in DNA repair by preferential recognization and elimination of damaged DNA.

Antineoplastic Agents, Alkylating↗

PubMed1998

Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma.

We immunohistochemically analyzed the expression of double-stranded RNA-dependent protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64 human liver biopsies and 25 liver sections of rats inoculated with diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers were minimum. Scoring signal intensity from 0-4, the average scores of chronic active (14 cases) and chronic persistent (6 cases) hepatitis associated with hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained cells were significantly more abundant in the periportal than centrilobular regions for both chronic active and persistent hepatitis (P < 0.001 each). The average score of liver cirrhosis associated with HCV was 1.9. Those scores of well-, moderately, and poorly differentiated hepatocellular carcinomas associated with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those scores of well- and poorly differentiated carcinomas associated with hepatitis virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR-positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end labeling method was approximately 20 in hepatitis, and over 100 in well-differentiated carcinoma.

Animals↗

PubMed1998

Involvement of cumulus cells stimulated by FSH in chromatin condensation and the activation of maturation-promoting factor in bovine oocytes.

The effects of FSH-stimulated cumulus cells on the regulatory mechanisms of chromatin condensation and maturation-promoting factor (MPF) activation around the time of germinal vesicle breakdown (GVBD) in bovine oocytes were examined. Chromatin condensation occurred in oocytes arrested at the germinal vesicle (GV) stage by protein synthesis inhibitor, cycloheximide, but this condensation was blocked by FSH-stimulated cumulus cells. However, treatment with cyclic AMP (cAMP)-dependent protein kinase inhibitor, H-8, dramatically increased the proportion of oocytes possessing GVs with condensed bivalents. Under the condition of inhibited protein synthesis, the phosphorylation form of p34cdc2 kinase was not changed due to chromatin condensation, although the activity of histone H1 kinase was significantly increased compared with that of oocytes possessing GVs with filamentous bivalents. The cycloheximide-dependent GVBD block was overcome by okadaic acid (OA) in 48 and 13% of the oocytes in the absence and presence of FSH, respectively. An initial 6-h culture period critical for protein synthesis was necessary for OA to counteract the inhibitory effect exerted by cycloheximide on the induction of GVBD and activation of histone H1 kinase in the absence of FSH, whereas this first culture period was prolonged for 2 h in the presence of FSH. Furthermore, even in FSH-stimulated oocytes, H-8 facilitated an OA-counteracted overcome of the cycloheximide-dependent GVBD block after 2 h of initial culture for protein synthesis. From these results, it is concluded that cAMP-dependent protein kinase activity regulated by cumulus cells following FSH-stimulation requests plays a role in the complex mechanism of chromatin condensation and MPF activation leading to meiotic resumption in bovine oocytes.

Animals↗

PubMed1998

Interaction of beta-lactam antibiotics with histidine residue of rat H+/peptide cotransporters, PEPT1 and PEPT2.

Peptide transporters mediate the H+-coupled uphill transport of oligopeptides and peptide-like drugs such as beta-lactam antibiotics in the intestinal and renal brush-border membranes. Two H+/peptide cotransporters, PEPT1 and PEPT2, have been cloned and functionally characterized. In this study, we examined the interaction of the dipeptides and beta-lactam antibiotics with the histidine residue of rat PEPT1 and PEPT2 transfected into the renal epithelial cell line LLC-PK1. Diethylpyrocarbonate (DEPC), which is a histidine residue modifier, abolished the glycylsarcosine uptake by both transfectants. The DEPC-induced inhibition of glycylsarcosine uptake via PEPT1 or PEPT2 was attenuated by an excess of dipeptide or aminocephalosporin. In contrast, anionic cephalosporins without an alpha-amino group and bestatin, which is an antineoplastic drug with a beta-amino group, did not attenuate the DEPC-induced inactivation of PEPT1 and PEPT2. The DEPC inactivation of PEPT1 was almost prevented by various charged dipeptides, which suggests that the inability of the drugs without an alpha-amino group to prevent the DEPC inactivation was not due to their ionic charge. These findings suggest that the alpha-amino group of beta-lactam antibiotics interacts with the histidine residue of PEPT1 and PEPT2 and may be involved in the mechanism of substrate recognition by the peptide transporters.

Animals↗

PubMed1998

Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan-1.

Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit the growth of a variety of cultured cells in a dose-dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined using an MTT assay and an in vivo tumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P < 0.05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.

Adenocarcinoma↗

PubMed1998

Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: an immunohistochemical study.

Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, alpha-catenin, beta-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin, and beta-catenin was the same or reduced when compared with non-cancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, alpha-catenin, and beta-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that beta-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5.

Adult↗

PubMed1998

Magnetic resonance signal intensity and volume changes after endovascular treatment of intracranial aneurysms causing mass effect.

To determine when and how intracranial aneurysms causing mass effect change following endovascular treatment, we used MRI to assess patients for 2-3 years after the interventional procedure. Nine patients who had aneurysms compressing the surrounding structures underwent endovascular treatment. Proximal occlusion of the parent artery was performed in seven cases, and in two the aneurysm was embolised with microcoils. After embolisation, signal intensity within aneurysms tended to be high on both T1- and T2-weighted images. When there was rapid reduction in size high-signal zones within aneurysms became isointense or gave low signal on T1-weighted images. On T2-weighted images, isointense or low-signal foci appeared within high-signal areas in the aneurysm, giving mixed intensity. In typical cases, the mean volume of the aneurysm fell to approximately 30% of its initial value 2-12 months after treatment. After this, no additional reduction was observed. The aneurysms which showed little signal intensity change tended to shrink more slowly and to a lesser degree than the more typical cases. Aneurysms which gave high signal on both T1- and T2-weighted images early following embolisation shrank more quickly than those showing little signal change.

Adult↗

PubMed1998

Carotid endarterectomy and simultaneous percutaneous transluminal angioplasty for tandem internal carotid stenoses.

We treated three patients with tandem internal carotid stenoses in single procedures including carotid endarterectomy (CEA) for the proximal stenosis and percutaneous transluminal angioplasty (PTA) for the distal stenosis. We devised a Y-shaped shunt tube for the CEA, through which a balloon catheter was introduced to perform PTA guided by mobile digital subtraction angiography. No cerebrovascular events occurred during follow-up. Our approach avoids the risk of a second procedure while effectively treating tandem stenoses.

Aged↗

PubMed1998

Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions.

We report 17 cases of intracranial arterial stenosis treated by percutaneous transluminal angioplasty (PTA), including 9 on the intracranial internal carotid (ICA), 4 on the middle cerebral (MCA), and 4 on vertebrobasilar artery (VBA) system. All patients had ischaemic brain symptoms and stenoses of more than 60% (calculated angiographically). We treated four patients by PTA for residual stenoses after thrombolysis for acute occlusion. We used PTA balloon catheters 2.0-3.5 mm in diameter for all procedures. As a rule, the balloon was inflated for 1 min at 6 atm. All arteries were successfully dilated (stenosis less than 50%) except for one treated by PTA for residual MCA stenosis after thrombolysis. The patient died of a massive infarct due to MCA reocclusion caused by arterial dissection. Stenosis recurred in 4 of 16 patients. Repeat PTA was successfully carried out in these cases. However, stenosis recurred in one of these patients 3 months after PTA, but the patient is being followed because he is asymptomatic. PTA of intracranial arteries is effective, but its indications should be based strictly on potential risks, such as acute occlusion derived from arterial dissection.

Aged↗

PubMed1998

The effect of oestrogen on the development of arteriovenous fistulae induced by venous hypertension in rats.

PURPOSE: Dural arteriovenous fistulae (AVF) represent abnormal communication between the meningeal arteries and the dural sinuses. Clinically, this condition appears more frequently in post-menopausal and pregnant women than in the general population. Oestrogen is believed to play an important role in the development of dural AVF; however, its exact role has not been clearly defined. We have previously reported that by surgically creating a carotid-jugular shunt in male rats, which then induces venous hypertension, spontaneous arteriovenous fistulae can result. To examine the specific role that oestrogen may have in the development of AVF induced by venous hypertension, we performed the following experimental procedure. MATERIALS AND METHODS: Ninety-four Sprague-Dawley female rats (250-300 grams in weight) were randomly assigned to four different groups. Group 1 (n = 20): control (bilateral ovariectomy only). Group 2 (n = 19): bilateral ovariectomy and implantation of the oestrogen pellet (17-beta oestradiol 0.75 mg/pellet, 60 days release). Group 3 (n = 17): bilateral ovariectomy and venous hypertension (left carotid-jugular shunt with proximal jugular vein occlusion). Group 4 (n = 38): bilateral ovariectomy and oestrogen pellet implantation and venous hypertension. All of the groups were examined by angiography 60 days after treatment. In Groups 1 and 2, bilateral common carotid angiography was performed via a transfemoral route. In Groups 3 and 4, angiography was done after surgical ligation of the carotid-jugular shunt to examine for any newly developed AVF. RESULTS: No newly developed AVF were found in either Groups 1, 2, or 3. In Group 4, 2 rats (5.3%) developed newly formed AVF which occurred in the nose and neck. Our previous study demonstrated that AVF appeared in 3 of 22 (13.6%) venous hypertensive male rats. Therefore, no statistical difference in the appearance rate of newly formed AVF was found among groups 1, 2, 3 or 4 and between our previously reported group of male venous hypertensive rats. CONCLUSION: In this experimental study, ovariectomy with or without oestrogen did not affect the development of spontaneous AVF induced by venous hypertension.

Animals↗

PubMed1998

Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development: a possible role in bile duct morphogenesis.

BACKGROUND/AIMS: Cell adhesion molecules play an important role in the morphogenesis of developing organs. However, little is known about their expression during intrahepatic bile duct development. METHODS: We immunohistochemically investigated the expression of E-cadherin (E-Cad), alpha-catenin (A-Cat) and beta-catenin (B-Cat) during human intrahepatic bile duct development, using 31 fetal livers of various gestational ages. The developmental stages of bile ducts were classified into the ductal plate, migrating biliary cells (remodeling stage), and immature bile ducts (remodeled stage). RESULTS: E-Cad was broadly and strongly expressed in the ductal plate with a cytoplasmic pattern, heterogeneously and weakly expressed in the migrating biliary cells with a cytoplasmic pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. A-Cat was broadly and strongly expressed in the ductal plate with a membrane pattern, broadly and moderately expressed in the migrating biliary cells with a membranous pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. In contrast, expression of B-Cat was weak or slight in the ductal plate, but B-Cat was expressed broadly and strongly with a membranous pattern in migrating biliary cells and in immature bile ducts. Immature hepatocytes rarely expressed E-Cad and A-Cat, but expressed B-Cat with a membranous pattern throughout development. CONCLUSIONS: These results suggest that E-Cad, A-Cat and B-Cat are involved in the normal developmental morphogenesis of human intrahepatic bile ducts.

Bile Ducts, Intrahepatic↗

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↗