Abstract. Cultured human lung fibroblasts produce a large, nonhydrophobic heparan sulfate proteoglycan that accumulates in the extracellular matrix of the monolayer (Heremans, A., J. J. Cassiman, H. Van den Berghe, and G. David. 1988. J. Biol. Chem. 263: 4731-4739). A panel of four monoclonal antibodies, specific for four distinct epitopes on the 400-kD core protein of this extracellular matrix heparan sulfate proteoglycan, detects similar proteoglycans in human epithelial cell cultures. Immunohistochemistry of human tissues with the monoclonal antibodies reveals that these proteoglycans are concentrated at cell-matrix interfaces. Immunogold labeling of ultracryosections of human skin indicates that the proteoglycan epitopes are nonhomogeneously distributed over the width of the basement membrane. Immunochemical investigations and amino acid sequence analysis indicate that the proteoglycan from the fibroblast matrix shares several structural features with the large, low density heparan sulfate proteoglycan isolated from the Engelbreth-Holm-Swarm sarcoma. Thus, both epithelial cell sheets and individual mesenchymal cells accumulate a large heparan sulfate proteoglycan(s) at the interface with the interstitial matrix, where the proteoglycan may adopt a specific topological orientation with respect to this matrix.
Background: In recent years, itraconazole pulse therapy for onychomycosis has been developed [three 1-week pulses with itraconazole 400 (2 × 200) mg daily every month]. This has proved an effective and safe regimen which requires only 50% of the medication used for continuous dosing schedules. Parallel to the development of the new dosage schedule, additional studies were conducted to further document the safety and efficacy of itraconazole 200 mg once daily for 3 months to treat onychomycosis. Objective: To compare the safety of itraconazole 200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly for a further 3 months, with that of miconazole cream twice daily for 6 months, in the treatment of onychomycosis. Treatment efficacy was compared as a secondary objective. Methods: In this multicenter, double-blind study, patients were randomized to receive itraconazole 200 mg once daily for 3 months followed by either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary variable was elevation of alanine aminotransferase (ALT) concentration above 50 U/l. Results: Overall incidence of elevation of ALT concentration above 50 U/l, adverse events and rate of withdrawal because of adverse events were low and similar in the three treatment groups. Efficacy was significantly greater in the ITR groups than the MIC-MIC group. Conclusion: Itraconazole and miconazole were well tolerated and had no significant effect on liver function, but itraconazole was significantly more effective.
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