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Background: Clinical information systems frequently use intranet and Internet technologies. However these technologies have emphasized sharing and not security, despite the sensitive and private nature of much health information. Digital certificates (electronic documents which recognize an entity or its attributes) can be used to control access in clinical intranet applications., Objectives: To outline the need for access control in distributed clinical database systems, to describe the use of digital certificates and security policies, and to propose the architecture for a system using digital certificates, cryptography and security policy to control access to clinical intranet applications., Methods: We have previously developed a security policy, DIMEDAC (Distributed Medical Database Access Control), which is compatible with emerging public key and privilege management infrastructure. In our implementation approach we propose the use of digital certificates, to be used in conjunction with DIMEDAC., Results: Our proposed access control system consists of two phases: the ways users gain their security credentials; and how these credentials are used to access medical data. Three types of digital certificates are used: identity certificates for authentication; attribute certificates for authorization; and access-rule certificates for propagation of access control policy. Once a user is identified and authenticated, subsequent access decisions are based on a combination of identity and attribute certificates, with access-rule certificates providing the policy framework., Conclusions: Access control in clinical intranet applications can be successfully and securely managed through the use of digital certificates and the DIMEDAC security policy.

A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

A rat fibroblast cell line, R6PKC3, that stably overexpresses the beta-1 form of protein kinase C was used to analyze sensitivity to inhibitors of epidermal growth factor (EGF) binding. R6PKC3 cells overexpress protein kinase C activity 53-fold relative to non-overexpressing control R6C1 cells. Inhibition of EGF binding by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) and photo-activated psoralens was compared in these cells. We found that 125I-EGF bound both of the cell lines and was rapidly internalized in a temperature-dependent process and metabolized. Binding of EGF to the R6 cells overexpressing protein kinase C was markedly less than binding to R6C1 control cells. In both of the cell lines, TPA and photoactivated psoralens inhibited 125I-EGF binding but the response of these cells to these inhibitors was distinct. R6PKC3 cells were markedly more sensitive to TPA and were resistant to recovery from TPA-induced inhibition of 125I-EGF binding when compared to control cells. These differences were not observed in other subclones of cells overexpressing protein kinase C, suggesting that they may be unique to R6PKC3 cells. In contrast, no major differences in sensitivity to photoactivated psoralens were observed in R6C1 and R6PKC3 cells. These data indicate that TPA and photoactivated psoralens inhibit 125I-EGF binding to these cell lines by distinct mechanisms.