Proliferating Cell Nuclear Antigen Expression in Peribiliary Glands of Stone-Containing Intrahepatic Bile Ducts

All cases of hepatolithiasis showed features ofchronic proliferative cholangitis, and it has beenspeculated that the atypical glandular proliferationmight be a precursor to overt cholangiocarcinoma. Proliferative cell nuclear antigen (PCNA) is anuclear protein synthesized in the G₁/S phaseof the cell cycle and therefore is related to cellproliferative activity. In an attempt to assess the activity of cell proliferation ofstone-containing intrahepatic bile ducts, we conducteda study using immunohistochemical staining withmonoclonal antibody to score PCNA in intrahepatic bileducts. Thirty patients (10 men, 20 women; mean age52.4 years) having hepatolithiasis surgically resectedwere studied. Ten stone-free patients served ascontrols. All 40 specimens were immunostained for PCNA using PC 10 monoclonal antibody. PCNA of bothstone-containing and stone-free intrahepatic bile ductswere assessed by counting positive staining nuclei per500 cells and expressed as labeling index (LI), ie, percentage of positive nuclei to the totalnumber of nuclei. The PCNA LI in stone-free intrahepaticbile ducts was generally low: 10.0 ± 13.2%, 10.4± 10.7% and 7.9 ± 9.6% for extramuralglands, intramural glands, and epithelial lining,respectively. In contrast, the PCNA LI forstone-containing intrahepatic bile ducts weresignificantly higher than those of controls (P <0.001): 49.4 ± 8.3%, 40.6 ± 7.0% and 34.1± 6.8% for extramural glands, intramural glands,and epithelial lining, respectively. The extramuralglands had a significantly higher PCNA LI (P < 0.001)than the intramural glands and controls. Hyperplasia was found inall specimens, while dysplasia was found in six of 30cases with hepatolithiasis. The dysplastic cells alsohad a higher PCNA LI (P < 0.001) than thehyperplastic cells and normal epithelium. Our findingsshowed that there is marked increase of activity of cellproliferation in stone-containing intrahepatic bileducts. It is well known that genetic mutations are facilitated in proliferating cells. Therefore,our results suggest that the high epithelial turnover indysplastic cells and extramural glands had higherpotential for proliferation and neoplastictransformation in long-standing untreatedhepatolithiasis.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Epstein-Barr Virus-encoded Latent Membrane Protein 1 Co-expresses with Epidermal Growth Factor Receptor in Nasopharyngeal Carcinoma

Latent membrane protein 1 (LMP-1) is the only Epstein-Barr virus (EBV)-encoded oncogenic protein that has been detected in nasopharyngeal carcinoma (NPC), a cancer that is closely associated with EBV. Previous in-vitro studies have demonstrated that LMP-1 can upregulate epidermal growth factor receptor (EGFR) in epithelial cells. It was not established whether this cellular effect exists in NPC. To assess the association between LMP-1 and EGFR in NPC tissues, 60 NPC specimens were examined by immunohistochemistry using anti-LMP-1 antibody (CS 1–4) and anti-EGFR antibodies (EGFR 1, EGFR 1005). The results revealed that 41 (68.3%) specimens were immunopositive for LMP-1 and 44 (73.3%) specimens over-expressed EGFR. Morphologically, the expressions of LMP-1 and EGFR were homogeneously distributed in the tumor nests. In addition, the correlation between LMP-1 and EGFR was statistically significant (P<0.001, χ² test, d.f.=1). To elucidate further the correlation between LMP-1 and EGFR in vivo and in situ , an indirect dual immunofluorescence assay was conducted, using secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or indocarbocyanine (Cy3). The results disclosed an intimate co-expression of LMP-1 and EGFR. In summary, the data indicate that over-expression of EGFR is a common phenomenon in NPC, and that EGFR is co-expressed with LMP-1 in NPC. Thus, EBV may play a role in the tumorigenesis of NPC through the effects of LMP-1 and EGFR.     

Clinical experiences of removing foreign bodies in the airway and esophagus with a rigid endoscope: a series of 3217 cases from 1970 to 1996.

This study examined 11,333 rigid endoscopy procedures performed in the Department of Otolaryngology, National Taiwan University Hospital, during a 27-year period from 1970 to 1996. Among these cases, 3217 were performed to remove foreign bodies from the airway (459 cases, 14.3%) and esophagus (2758 cases, 85.7%). Retrospective analysis of these data revealed that peanuts (217 cases) and animal bones (1184 cases) were the most frequent foreign bodies encountered in the airway and esophagus, respectively. The successful rate of removal of these foreign bodies was 99.9% (3213/3217). The complication rate was only 0.2% (8/3217), and the mortality rate was less than 0.1% (2/3217). On the basis of these results, we conclude that foreign bodies in the airway and esophagus can be removed safely under direct visualization through rigid endoscopy with relatively few complications. A significant finding in this study is the declining trend in the number of cases in recent years. Despite the decline in the number of procedures, endoscopic removal of foreign bodies remains as a vital skill of the aerodigestive tract surgeon.     

Prevalence of antibodies to hepatitis C virus in the hemodialysis unit.

An enzyme immunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 261 patients and 69 staff members of a hemodialysis unit. The prevalence of anti-HCV was 46.7% in patients and 2.9% in staff members (p less than 0.001). The prevalence of anti-HCV increased significantly with increasing duration of hemodialysis (p less than 0.001), but was not related to age, sex, history of blood transfusion, status of hepatitis B or hepatitis A virus infection, or serum ALT. Patients with hepatitis episode increased with increasing duration of hemodialysis and showed a significantly higher prevalence of anti-HCV than those without (63.1 vs. 34.7%, p less than 0.001). The prevalence of anti-HCV in patients with hepatitis also increased with increasing duration of hemodialysis (p = 0.05). Thus, HCV appears to be the major cause of hepatitis in hemodialysis patients. Besides strict infection control measures, further studies are needed to determine the mode of HCV infection and its prevention in the hemodialysis unit.     

A liver slice culture-based ex vivo assay to predict the outcome of antiviral therapy for chronic hepatitis C

Summary.  A liver slice culture-based, ex vivo drug suppression assay was developed as a pre-therapeutic predictor for the outcome of antiviral therapy. To investigate its clinical application, 106 consecutive patients with chronic hepatitis C virus (HCV) infection were evaluated. Ex vivo drug suppression assay was performed before administrating a standard course of peginterferon plus ribavirin combination therapy. Stepwise logistic regression model was used to estimate sustained virological response (SVR) on the presence of various clinicopathological parameters. Suppression of HCV replication in the ex vivo assay was present in 32 patients, 29 (90.6%) of whom achieved SVR. Stepwise logistic regression analysis indicated that the presence of interferon suppression effect in the ex vivo assay (odds ratio [OR], 5.552; 95% confidence interval [CI], 1.114–27.673; P  = 0.036), genotype 1 (OR; 0.045, 95% CI, 0.008–0.259; P  = 0.001), HCV-RNA level (OR, 0.739; 95% CI, 0.617–0.885; P  = 0.001), the presence of fatty metamorphosis (OR, 0.205; 95% CI, 0.053–0.793; P  = 0.022), and albumin (OR, 9.687; 95% CI, 2.237–41.940; P  = 0.002) were independent determinants of SVR. Categorical analysis revealed that 17 of 17 (100%) patients with genotype non-1 and positive ex vivo suppression test achieved SVR, while 20 of 40 (50%) with genotype 1 and negative ex vivo suppression test achieved SVR. In conclusion, the ex vivo drug suppression assay may serve as an independent pre-therapeutic predictor for the SVR in interferon-based antiviral therapy.     

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.