No abstract

Interaction with E,a led to the discovery of the E,s (Liddell et al., 1962) and Eli variants. E,s exists in several forms (Rubinstein et al., 1970) and results in 95 to 100% diminution of E u molecules; E,J results in about 66% reduction. One family has been described in which several members have greatly increased amounts of apparently normal serum cholinesterase (Neitlich, 1966;Yoshida and Motulsky, 1969). The gene responsible has been named E Cynthiana but it is not yet known if it is active at cholinesterase locus 1 or locus 2.We present here two families with a quantitative variant at cholinesterase locus 1 which results in about 33% reduction of E,u molecules; both of these families were recognised by means of interaction with the E, a gene. MethodsThe enzymatic and immunological methods used were the same as given in earlier publications Rubinstein et al., 1976;Dietz et al., 1973). (Table II

Peyronie's disease is a fibromatosis of the tunica albuginea. While trauma is believed to be the inciting event, the exact pathophysiology of this condition is unknown. In vitro analysis of cell biology can shed light on the pathogenesis of medical conditions and has been used for many decades as a research tool. We have established a cell culture model, which we have used to study the pathobiology of cells derived from Peyronie's disease plaque tissue. In 10 separate cell cultures derived from different individuals, these cells have demonstrated consistent phenotypic, genotypic and functional alterations. In neither of the control cell cultures, neonatal foreskin fibroblasts and normal tunica-derived fibroblasts have any of the above aberrations been demonstrated. The cells studied have been shown to be fibroblasts in nature with a sub-population of myofibroblasts present in culture. The Peyronie's disease plaque tissue-derived fibroblasts have demonstrated (i) consistent morphologic transformation (ii) increased S-phase on flow cytometry (iii) decreased dependence on culture medium (iv) cytogenic instability (v) excess production of fibrogenic cytokines and (vi) stabilization and dysfunctionalization of p53. Further refinement of this model and future analyses may permit an increased understanding of the pathogenesis of this condition and allow the development of therapeutic strategies.

Peyronie's disease is a ®bromatosis of the tunica albuginea which affects up to 2% of men. Plaque development is believed to result, at least in part, from ®broblast proliferation and excess collagen deposition. Numerous oral and intralesional therapies have been used, including verapamil, colchicine and steroids. The purpose of this study was to investigate the in vitro effects of prostaglandin-E1 (PGE1), verapamil and colchicine on the proliferation rates of ®broblasts derived from Peyronie's disease tissue.Using tissue culture, multiple cell lines comprising ®broblasts from Peyronie's plaque, normal tunica and foreskin were established. Cells of low passage were removed from the parent culture and incubated with varying concentrations of PGE1 (0.1 ± 10 mgaml), verapamil (10 ± 1000 mgaml), and colchine (2.5 mgaml). Proliferation was assessed at 48, 72 and 96 hours using the Vybrant TM MTT cell proliferation and then compared to control cells.Six plaque lines and 5 normal tunical cell lines were established. These cell lines exhibited excellent linear growth in culture media alone. Co-culture wih PGE1 resulted in no signi®cant inhibition at 0.1 and 1 mgaml, but a mean inhibition of 60.6 AE 11.5% at a concenrtation of 10 mgaml was noted. Similar inhibition was noted with verapamil at 100 and 1000 mgaml with a mean inhibition of 65.2 AE 10.6%. Colchicine resulted in a mean inhibition of 28% at a concentration of 2.5 mgaml. Maximum inhibition occurred at 96 hours in all cases. There was no statisitically signi®cant difference in proliferation rates between plaque and normal tunical cell lines.We have developed an in vitro model to assess the effects of biologically active agents on the growth of ®broblasts derived from Peyronie's disease tissue. Our data suggests that PGE1, verapamil, and colchicine inhibit in vitro proliferation of ®broblasts at speci®c concentrations. Re®nement and application of this knowledge may allow the development of useful pharmacologic strategies for men with PD.

These data demonstrate the successful establishment of cell lines from plaque tissue and normal tunica from men with Peyronie's disease. The findings indicate a potential role for basic FGF over expression in the tunical fibrosis that occurs in this condition. This information may allow a better understanding of the basic mechanisms involved in the development of this disease. Furthermore, it may permit the elaboration of therapeutic strategies to prevent or reduce tunical scarring and plaque formation.