Is hypertension associated with hemifacial spasm?
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Y Han
Publications and source records attributed to S Y Han.
Anemia following renal transplantation.
Explore the source record for details and available documents.
Anemia↗
Primary immunosuppression with tacrolimus in renal transplantation: a single center experience.
Explore the source record for details and available documents.
Drug Therapy, Combination↗
Piribedil and bromocriptine in Parkinson's disease: a single-blind crossover study.
INTRODUCTION: Clinicians switch from one dopamine agonist to another for various reasons. However, each change may inadvertently result in certain potential risks such as decreased medication efficacy or new side-effects. OBJECTIVE: We evaluated the tolerability of a switch of bromocriptine to piribedil using two conversion ratios as a primary outcome measure, with motor function as a secondary outcome measure, in patients with mild to moderate Parkinson's disease (PD). METHODS: Twenty consecutive patients with mild to moderate PD (Hoehn and Yahr, stage II-III) on treatment with stable doses of bromocriptine and levodopa were randomized to two groups of 10 patients each, to receive piribedil based on 1:5 or 1:10 conversion ratios. Blinded evaluations were performed: 1) United Parkinson's Diseased Rating Scale (UPDRS) scores both in 'on' and 'off', 2) Open-ended interviews for adverse events, 3) Epworth Sleepiness Scale, 4) Purdue Pegboard assessment during 'on' and 'off', 5) Hand-arm movement test during 'on' and 'off', and 6) Walking test during 'on' and 'off'. RESULTS: Major adverse events included 'sleep attacks' in one patient and minor side-effects included giddiness, nausea, hallucinations, sleepiness and lethargy. However, these were mild and 19 (95%) of the 20 patients completed the study. There was a significant improvement in both the UPDRS 'off' total and motor scores at 1 month compared with baseline for the group on 1:10 ratio. The walking times during the 'off' state at 1 and 2 months were significantly better compared with baseline in the 1:5 group. There were otherwise no significant differences in the rating tests during both 'off' and 'on' states before and after the bromocriptine switch. CONCLUSIONS: We demonstrated that patients with mild to moderate PD who were on relatively low doses of bromocriptine can be safely switched to piribedil based on a conversion ratio of either 1:5 or 1:10. However, the higher conversion ratio has to be carried out with caution in patients with daytime somnolence.
Administration, Oral↗
Bioavailability and mammary excretion of bisphenol a in Sprague-Dawley rats.
This study reports the absolute oral bioavailability and mammary excretion of bisphenol A in rats. The oral bioavailability was determined after administration of relatively low iv (0.1 mg/kg) and oral (10 mg/kg) doses of bisphenol A to rats. After iv injection, serum levels of bisphenol A declined biexponentially, with the mean initial distribution and terminal elimination half-lives being 6.1 +/- 1.3 min and 52.5 +/- 2.4 min, respectively. The systemic clearance (Cls) and the steady-state volume of distribution (Vss) averaged 107.9 +/- 28.7 m/min/kg and 5.6 +/- 2.4 L/kg, respectively. Upon oral administration, the maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 14.7 +/- 10.9 ng/ml and 0.2 +/- 0.2 h, respectively. The apparent terminal elimination half-life of bisphenol A (21.3 +/- 7.4 h) after oral administration was significantly longer than that after iv injection, indicating the flip-flop of the absorption and elimination rates. The absolute oral bioavailability of bisphenol A was low (5.3 +/- 2.1%). To determine the extent of mammary excretion, bisphenol A was given by simultaneous iv bolus injection plus infusion to steady state at low, medium, and high doses. The steady-state serum levels of bisphenol A were linearly increased with higher dosing rates. The systemic clearance (mean range, 119.2-154.1 ml/min/kg) remained unaltered over the dosing rate studied. The levels of bisphenol A in milk exceeded those in serum, with the steady-state milk to serum concentration ratio being 2.4-2.7.
Administration, Oral↗
Cell type-dependent regulation of human DNA topoisomerase III alpha gene expression by upstream stimulatory factor 2.
Here, we report that an E-box element located within the human topoisomerase III alpha (hTOP3 alpha) gene promoter acts as a cell type-specific enhancer. The upstream stimulatory factor (USF) was shown to specifically recognize the mutationally sensitive E-box element. When assayed by transient transfection with hTOP3 alpha promoter-dependent reporter genes, USF is transcriptionally active in HeLa cells but lacks transcriptional activity in Saos-2 cells. The hTOP3 alpha mRNA level in Saos-2 cells was reduced to about 30% of the level observed for HeLa cells, suggesting that the inactivity of USF in hTOP3 alpha promoter activity may be the cause of the marked reduction of hTOP3 alpha mRNA levels in Saos-2 cells. Using transient transfection assays in HeLa cells, we demonstrated that ectopically expressed USF2, but not USF1, was capable of activating hTOP3 alpha transcription through the E-box element. However, USF2 did not stimulate hTOP3 alpha promoter activity in Saos-2 cells. This cell type-specific regulation of promoter activity by USF2 may provide a mechanism for the differential expression of hTOP3 alpha in various tissues and during developmental stages.
Base Sequence↗
Regulation of mouse DNA topoisomerase IIIalpha gene expression by YY1 and USF transcription factors.
To investigate the mechanisms responsible for the regulation of DNA topoisomerase IIIalpha (TOP3alpha) gene expression, the promoter region of the mouse gene has been cloned and analyzed. The promoter region is moderately high in GC content and lacks a canonical TATA box, typical for promoters of a number of housekeeping genes. Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequences demonstrated that the 34-bp region from -137 to -170 upstream of the transcription initiation site contains a positive regulatory element(s) for the efficient expression of mouse TOP3alpha gene. Combined analyses by gel mobility shift and supershift assays revealed that both YY1 and USF transcription factors were capable of binding to the 34-bp region. When YY1 and USF-binding elements were selectively mutated, the luciferase activity of the resulted constructs was greatly reduced, indicating that both YY1 and USF function as transcriptional activators. Interestingly, YY1 and USF-binding elements are conserved in both human and mouse TOP3alpha promoters. This suggests that mammalian TOP3alpha genes may possess a common mechanism of transcription regulation through these elements.
3T3 Cells↗
Lysophosphatidylcholine derived from deer antler extract suppresses hyphal transition in Candida albicans through MAP kinase pathway.
A family of 2-lysophosphatidylcholines (lyso-PCs) was isolated from deer antler extract, guided exclusively by hyphal transition inhibitory activity in Candida albicans. Structural determination of the isolated lyso-PCs by spectroscopic methods, including infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, 2D correlation spectroscopy NMR, fast atom bombardment mass spectrometry and tandem mass spectrometry, confirmed that the natural products were composed of at least four different lyso-PCs varying in fatty acid moiety at the sn-1 position of the glycerol backbone. The major lyso-PCs were confirmed as 1-stearoyl-, 1-oleoyl-, 1-linoleoyl- and 1-palmitoyl-2-lyso-sn-glycero-3-phosphatidylcholines. Lyso-PC specifically suppressed the morphogenic transition from yeast to hyphae in C. albicans, without affecting the growth of either yeast or hyphae. Lyso-PC exerted hyphal transition that suppressed activity in the broad spectrum of the Candida species, such as C. albicans, Candida krusei, Candida guilliermondii and Candida parapsilosis. Northern analysis indicated that the suppression was mediated through the mitogen-activated protein kinase pathway.
Animals↗
Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.
Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.
Humans↗
Induction of cytosolic phospholipase A2 by oncogenic Ras is mediated through the JNK and ERK pathways in rat epithelial cells.
Mutations in ras genes have been detected with high frequency in nonsmall cell lung cancer cells (NSCLC) and contribute to transformed growth of these cells. It has previously been shown that expression of oncogenic forms of Ras in these cells is associated with elevated expression of cytosolic phospholipase A(2) (cPLA(2)) and cyclooxygenase-2 (COX-2), resulting in high constitutive levels of prostaglandin production. To determine whether expression of constitutively active Ras is sufficient to induce expression of these enzymes in nontransformed cells, normal lung epithelial cells were transfected with H-Ras. Stable expression of H-Ras increased expression of cPLA(2) and COX-2 protein. Transient transfection with H-Ras increased promoter activity for both enzymes. H-Ras expression also activated all three families of MAP kinase: ERKs, JNKs, and p38 MAP kinase. Expression of constitutively active Raf did not increase either cPLA(2) or COX-2 promoter activity, but inhibition of the ERK pathway with pharmacological agents or expression of dominant negative ERK partially blocked the H-Ras-mediated induction of cPLA(2) promoter activity. Expression of dominant negative JNK kinases decreased cPLA(2) promoter activity in NSCLC cell lines and inhibited H-Ras-mediated induction in normal epithelial cells, whereas expression of constructs encoding constitutively active JNKs increased promoter activity. Inhibition of p38 MAP kinase or NF-kappaB had no effect on cPLA(2) expression. Truncational analysis revealed that the region of the cPLA(2) promoter from -58 to +12 contained sufficient elements to mediate H-Ras induction. We conclude that expression of oncogenic forms of Ras directly increases cPLA(2) expression in normal epithelial cells through activation of the JNK and ERK pathways.
Animals↗
Frequent nuclear accumulation of beta-catenin in pituitary adenoma.
BACKGROUND: Beta-catenin (CTNNB1) is known to be a member of the cadherin-catenin superfamily and to function in cell-cell adhesion. However, it also has been reported that CTNNB1 plays an important role in carcinogenesis. In the current study, the authors observed expression of the CTNNB1 protein in primary pituitary adenomas to investigate the role of CTNNB1 in the development of pituitary adenomas. METHODS: A total of 37 pituitary adenomas were analyzed. Expression of CTNNB1 and the cell proliferation marker Ki-67 were observed immunohistochemically. In addition, the authors performed direct sequencing to detect somatic mutations of exon 3 of the CTNNB1 gene. RESULTS: Twenty-one of 37 pituitary adenomas (57%) demonstrated abnormal nuclear accumulation of CTNNB1. It is interesting to note that tumors with an accumulation of CTNNB1 in the nucleus showed a statistical tendency toward an association with increased immunoreactivity of Ki-67 (P < 0.05) whereas no significant correlation was detected between the status of CTNNB1 and other clinicopathologic features. Missense mutations in exon 3 of the CTNNB1 gene also were detected in the cases with abnormal nuclear accumulation of the CTNNB1 protein. CONCLUSIONS: The results of the current study suggest that up-regulation of the Wnt signaling pathway, including accumulation of mutant CTNNB1 in the nuclei, plays an important role in the tumorigenesis and development of adenoma in the pituitary gland.
Adenoma↗
Expression of Fas and Fas-related molecules in human hepatocellular carcinoma.
Many tumor cells, including hepatocellular carcinoma (HCC), express both Fas and its ligand on their surfaces, and it has remained a mystery why such cells do not spontaneously become apoptotic. In the current study, we analyzed the alterations of Fas structure and the expression of Fas and Fas ligand (FasL) and of Fas pathway inhibitors, including soluble Fas (sFas), Fas-associated phosphatase-1 (FAP-1), and bcl-2, in 50 cases of human HCC. Monoallelic loss of the Fas gene, as determined by loss of heterozygosity with intragenic polymorphisms, was observed in 5 of the 34 informative cases (15%), but none of the 50 cases showed Fas gene mutation. Expression of Fas and FasL was detected in 44 (88%) and 50 (100%) cases, respectively. sFas messenger RNA, as analyzed by in situ reverse-transcription polymerase chain reaction was expressed in 42 of the 50 cases (84%), and FAP-1 expression was observed in 40 of the 50 cases (80%). In contrast, none of the 50 cases showed bcl-2 expression. Our results showed that the majority of the HCCs (88%) coexpressed a death receptor, Fas and its cognate ligand, FasL, but all HCCs showed one or more alterations of the Fas pathway molecules known to inhibit Fas-mediated apoptosis. These findings suggest that the expression of sFas and FAP-1 and, in part, loss of Fas expression, rather than Fas gene alteration or bcl-2 expression, may be involved in the Fas resistance of HCC in vivo and that these mechanisms may play important roles in the pathogenesis of human HCC. HUM PATHOL 32:250-256.
Adult↗
An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.
OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.
Adult↗
The relationship between amniotic fluid matrix metalloproteinase-8 and funisitis.
OBJECTIVE: The fetal inflammatory response syndrome is a multisystem disorder associated with impending preterm delivery and adverse neonatal outcome. Inflammation of the umbilical cord--funisitis--is the histologic counterpart of fetal inflammatory response syndrome and has been associated with an increased risk for the development of cerebral palsy. Neutrophils found in the amniotic cavity are of fetal origin. Therefore, neutrophil secretory products may be an index of the fetal inflammatory response syndrome. To test this hypothesis, we examined the relationship between levels of amniotic fluid matrix metalloproteinase-8 and funisitis. STUDY DESIGN: The relationship between the presence of funisitis and concentrations of amniotic fluid matrix metalloproteinase-8 was examined in 255 consecutive patients who delivered preterm singleton neonates (gestational age, <36 weeks) within 72 hours of amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Matrix metalloproteinase-8 was measured by use of a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: Funisitis was present in 23% (59/255) of cases. Patients with funisitis had a significantly higher median concentration of amniotic fluid matrix metalloproteinase-8 than those without funisitis (median, 433.7 ng/mL [range, 1.5-3836.8 ng/mL] vs median, 1.9 ng/mL [range, <0.3-4202.7 ng/mL]; P <.001). The diagnostic indices of matrix metalloproteinase-8 (cutoff, 23 ng/mL) in the identification of funisitis were: sensitivity of 90% (53/59), specificity of 78% (153/196), positive predictive value of 55% (53/96), and negative predictive value of 96% (153/159). CONCLUSIONS: There is a strong association between increased levels of amniotic fluid matrix metalloproteinase-8 and funisitis. We propose that determination of amniotic fluid matrix metalloproteinase-8 concentrations may assist the assessment of the fetal inflammatory status, thereby eliminating the need for fetal blood sampling.
Adult↗
The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibronectin.
OBJECTIVE: A positive fetal fibronectin result in cervicovaginal fluid is a powerful predictor of preterm delivery and is considered a marker for upper genital tract infection (ie, intrauterine infection). Treatment with antimicrobial agents is being considered in patients with a positive fetal fibronectin test of cervico/vaginal fluid. This study was undertaken to determine the frequency and clinical significance of intra-amniotic infection/inflammation in patients with a positive fetal fibronectin. STUDY DESIGN: A total of 1709 pregnant women (gestational age, 23-31 weeks) were screened for cervical fetal fibronectin. Patients with a positive fibronectin were offered amniocentesis for the diagnosis of intra-amniotic infection and treatment with antibiotics. Amniocentesis was performed in 58 patients with a positive fibronectin test (>50 ng/mL). Amniotic fluid was cultured for aerobic/anaerobic bacteria and mycoplasmas. Polymerase chain reaction assay for Ureaplasma urealyticum was performed. Interleukin-6 concentrations were measured by a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: None of the patients with a positive fibronectin had a positive amniotic fluid culture. U urealyticum was detected in 1 case (1.8%) with the polymerase chain reaction assay. Amniotic fluid IL-6 was elevated (>2.5 ng/mL) in 5.3% of patients (3/57 patients); all of these patients delivered preterm neonates. There was no relationship between amniotic fluid IL-6 and cervical fibronectin concentration (r = 0.14;P: >.1). Patients who delivered preterm (<34 weeks) had higher median amniotic fluid IL-6 and cervical fetal fibronectin concentrations than those patients who delivered after 34 weeks (IL-6: median, 2.1 ng/mL [range, 0.1-25.3 ng/mL] vs median, 0.3 ng/mL [0.03-2.4 ng/mL]; P <.05; fibronectin: median, 509 ng/mL [260->1000 ng/mL] vs median, 155 ng/mL [50-889 ng/mL]; P <.01). CONCLUSION: Intra-amniotic infection was detected in 1.8% of cases with a positive fibronectin in the cervical fluid; intra-amniotic inflammation was present in 5.3% of cases. All patients with a positive fetal fibronectin and intra-amniotic inflammation delivered preterm neonates.
Adult↗
TFIIAalpha/beta-like factor is encoded by a germ cell-specific gene whose expression is up-regulated with other general transcription factors during spermatogenesis in the mouse.
TFIIAalpha/beta-like factor (ALF) is a testis-specific counterpart of the large subunit of human general transcription factor TFIIA. Northern analysis shows that ALF mRNA first appears in mouse testis at Postnatal Day 14. Similarly, expression of the general transcription factors TBP, TRF2, TFIIAalpha/beta, TFIIAgamma, and TFIIIB(90) is also increased beginning at Postnatal Day 14, suggesting that there is a coordinated induction of many general transcription factors during male germ cell differentiation. Analysis of male germ cells separated by Staput sedimentation shows that ALF is present in pachytene spermatocytes and haploid spermatids. In addition, in situ hybridization experiments with adult mouse testis shows that ALF is present in haploid spermatids. Searches of the human genome sequence database using the basic local alignment search tool reveal that the ALF and TFIIAalpha/beta(GTF2A1) genes are both composed of nine exons, whereas the TFIIAgamma (GTF2A2) gene is composed of five exons. Furthermore, nucleotide and amino acid comparisons among human and mouse ALF, TFIIAalpha/beta, and TFIIAgamma cDNA sequences show that ALF has diverged more rapidly than either TFIIAalpha/beta or TFIIAgamma. Finally, the ALF and SBLF (Stoned B-Like Factor) sequences present in the chimeric SALF cDNA are both present on human chromosome 2, and an analysis of the corresponding genes suggests a model for the formation of SALF.
Amino Acid Sequence↗
Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.
The potential estrogenic activities of bisphenol-A were investigated in vitro (E-screen and estrogen receptor competitive binding bioassays) and in vivo (uterotrophic assay). Uterotrophic responses were evaluated using mature ovariectomized Sprague-Dawley female rats treated subcutaneously with bisphenol A (1, 5, 10, 50, and 100 mg/kg/day), E2 (0.3 microgram/kg), and DES (0.3 microgram/kg) for 3 consecutive days. In a MCF-7 cell proliferation assay, E2 and DES used as positive estrogens induced maximum proliferation of MCF-7 cells at 1.0 nM, whereas BPA slightly induced MCF-7 cell proliferation at a higher level of 0.1 microM and maximum proliferation at 10 microM. In a competitive binding assay, E2 and DES showed inhibition of 17 beta-[3H]estradiol binding to the rat uterus ER with an IC50 of 1.0 nM and 0.5 nM, respectively. However, BPA had an IC50 of 5 microM, which was approximately 5,000 or 10,000-fold greater than the IC50 of E2 and DES. In uterotrophic assays, uterus (wet and blotted) and vagina weights were significantly increased at the dose of BPA 100 mg/kg/day in OVX Sprague-Dawley rats. These studies demonstrate that BPA exhibits weak estrogenic activity in all experimental systems, and thus its migration from epoxy resins or polycarbonate products should be controlled not to exceed a safety levels for humans.
Animals↗
Altered remodeling of nucleolar machineries in cultured hepatocytes treated with thioacetamide.
Thioacetamide (TA) is converted into a hyperacetylating agent which causes hepatic necrosis, regeneration, cirrhosis and cancerous transformation. One of the most characteristic toxicities of TA in rat is observed with a 50 mg/kg per day which induces nucleolar enlargement different from that in regenerating liver. From TA-treated liver, the nucleoli were isolated and characterized for an altered nucleolar signal transduction system. Immunochemistry revealed that the poisoned nucleoli had increased levels of both nucleolus specific proteins (nucleophosmin and nucleolin) and various signal molecules (CK2, Erk1/2, p38, protein kinases A and C, and cyclin A). Using flow cytometry, the nucleoli were found to be in G2-arrested nuclei. Manifestation of the nucleolar enlargement could be readily observed using an ex vivo hepatocyte culture. There were two types of nucleolar enlargement. One was observed in normal hepatocytes with light density of enlarged nucleoli. The other was in TA-treated hepatocytes with dense and compact density of enlarged nucleoli, which contained a 3 to 5-fold higher nudeophosmin content than the control. In vitro induction of nucleolar enlargement with TA was possible. As soon as the hepatocytes anchored on a collagen coat, exogeneous TA (higher than 1 microg/mL) could induce dense and compact nucleoli. However, when an exogeneous drug was added after monolayer formation (1 day), no drug-induced nucleolar enlargement was observed.
Animals↗