AIM:To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS:Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS:Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION:The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at preinterferon treatment might be risk factors for developing HCC after SVR.

It has been reported that oxygen-derived free radicals play an important role in the pathogenesis of mucosal injury in the small intestine as well as in the stomach. The aims of this study were to test whether ethanol-induced damage in the rat stomach was prevented by the administration of (1) superoxide dismutase (SOD; a scavenger of superoxide radicals), (2) allopurionol (ALP; an inhibitor of xanthine oxidase), (3) dimethyl sulfoxide (DMSO; a scavenger of hydroxyl radicals). SOD significantly decreased the ulcer index from 100 +/- 8.5% (control) to 39.6 +/- 8.2% (P less than 0.001). Ethanol-induced damage was reduced by the administration of ALP by 37.4% (P less than 0.01). DMSO also diminished the ulcer index from 100 +/- 8.5% (control) to 31.6 +/- 5.8% (P less than 0.01). Histochemical studies supported these results. A scanning EM study, however, revealed that surface epithelial cells were not protected by SOD against ethanol-induced damage. These results demonstrated that SOD, ALP and DMSO had the ability to protect gastric mucosa against ethanol-induced injury. Accordingly, oxygen-derived free radicals may be involved in the pathogenesis of ethanol-induced gastric mucosal damage. Surface epithelial cells, however, were not protected even by SOD against ethanol-induced injury.

Background -Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. Methods -Suspensions of silica particles were transnasally administered to nude athymic mice (BalbIc nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. Results -Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) gg hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) ftg/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43)

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Aims-To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. Methods-Sixteen cases ofpapilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. Results-HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 114 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases ofdysplasia and squamous cell carcinoma. The mean age ofHPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p<0.01).Conclusions-Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events.(J Clin Pathol 1995;48:1106-1 1 10)

The purpose of this study was to investigate the morphological and physiological effects of tetraprenylacetone (TPA) on ethanol(ET)-induced injury in rat gastric mucosa. Fasted rats received orally the following agents; a) vehicle (VH); b) 50, 100, or 200 mg/kg of TPA; c) indomethacin (IDM, 5 mg/kg), 30 min prior to TPA (200 mg/kg). Thirty minutes later, 1 ml of absolute ET was administered into the rat stomach. The gastric mucosa was assessed at 60 min after administration of ET. The ulcer index was significantly decreased by TPA in a dose-related fashion when compared with controls. Histological studies also showed significant reduction of ET-induced mucosal damage by TPA. A scanning electron microscopic study revealed that, when TPA was administered, surface epithelial cells of fundic mucosa were protected against ET-induced injury. The decrease of potential difference induced by ET was diminished by TPA (p < 0.01). Addition of IDM significantly reduced the effect of TPA. This indicates that TPA has a protective effect on rat gastric mucosa against ET-induced injury. The data also suggested that endogenous prostaglandins may be partially involved in this effect of TPA.

The transnasal administration of an extract of the parasite Ascaris suum (Asc) to C57BL/6 mice for 3 wk produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. This pulmonary eosinophilia was not accompanied by blood eosinophilia. The oral administration of cyclosporin, 50 mg/kg body weight, every other day significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB X C57BL/6)F1-W/WV (W/WV) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of eosinophilia in BAL in this model. C57BL/6, W/WV, and Balb-C mice that developed eosinophilia in the BAL also showed elevated total IgE levels and IgE titers against Asc in the sera. On the other hand, C57BL/6-nu/nu mice and IgE low-responder SJL mice, which developed little eosinophilia, did not show elevated total IgE levels and IgE titers against Asc in the sera. However, oral administration of cyclosporin, 50 mg/kg, which inhibited eosinophilia in the BAL in C57BL/6 mice, did not significantly inhibit the elevation of total IgE or IgE against Asc in the sera. This indicates that serum IgE production is not required for the formation of eosinophilia.

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