We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.

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Aim-To evaluate the expression pattern of glial cell line-derived neurotrophic factor (GDNF) with its receptors GDNF family receptor alpha-1 (GFRα-1) and Ret in the human corneal and limbal tissues, as well as in the primary human limbal epithelial cultures (PHLEC).Methods-Expression of GDNF and its receptors, and the co-localisation with stem cell associated and differentiation markers were evaluated by immunofluorescent staining, western blot analysis and real-time PCR in the fresh human corneoscleral tissues, as well as in the PHLEC. Single cell colony-forming and wound-healing assays were also evaluated in PHLEC.Results-GDNF and GFRα-1 were found to be expressed by a subset of basal cells and colocalised with ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2) and p63, but not with cytokeratin 3 in the human limbal basal epithelium. In PHLEC, they were expressed by a small population of cells in the less differentiated stage. The GDNF and GFRα-1-positive subpopulations were enriched for the expression of ABCG2 and p63 (p<0.01). Recombinant human GDNF promoted the proliferation and wound healing of epithelial cells in the PHLEC. In contrast, Ret was abundantly located in the human corneal epithelium except for the basal cells of the limbal epithelium.Conclusion-These findings indicate that GDNF and GFRα-1 may represent a property for the phenotype of human corneal epithelial precursor cells. GDNF may signal independently of Ret through GFRα-1 in the stem cell-containing limbal epithelium.Glial cell line-derived neurotrophic factor (GDNF) is a member of the GDNF family of neurotrophic factors, which also includes neurturin, artemin and persephin. 1 GDNF exerts its effects through a multicomponent receptor system consisting of the GDNF family receptor alpha-1 (GFRα-1), Ret receptor tyrosine kinase (Ret) and neural cell adhesion molecule (NCAM).2 3 GDNF has been shown to support the growth, maintenance and differentiation of a wide variety of neuronal systems. In recent years, GDNF was identified as an essential growth factor maintaining mouse spermatogonial stem cells,4 and it was found to increase motility and survival of cultured mesenchymal stem cells and ameliorate Corneal epithelial homeostasis is governed by a small subpopulation of corneal epithelial SCs located in the basal layer of the limbus.6 -8 However, no direct method has been found to identify the corneal epithelial SCs to date because of the lack of a unique molecular marker. In recent years, the functional role and the possible signal-transduction pathways induced by GDNF in the corneal epithelium have been investigated.9 10 GDNF may play an important role in corneal regeneration and wound healing. In the present study, we evaluated the expression pattern of GDNF with its receptors in the human corneal and limbal epithelia, as well as in the primary limbal epithelial cell cultures (PHLEC), with the intention of exploring the potential role of GDNF in the human stem cell niche. MATERIALS AND METHODS Materials and reagentsProgenit...