The c‐fos proto‐oncogene is rapidly and transiently induced by a variety of extracellular stimuli. We have previously shown that conditioned media from v‐sis transformed NRK cells rapidly induces a DNA binding protein which binds to a conserved sequence upstream of the human c‐fos gene. We now show that purified recombinant c‐sis/PDGF can induce this binding activity which we have termed SIF, for sis‐inducible factor. Oligonucleotides which bind to the SIF protein will confer sis/PDGF inducibility onto a truncated, unresponsive c‐fos promoter. However, sequences lying between ‐100 and ‐57 of the c‐fos gene are required for this induction. The sis‐responsive element functions independently of a region of dyad symmetry previously identified as the serum responsive element (SRE). The time course of c‐fos expression driven by the sis‐responsive element is similar to that mediated by the SRE. Unlike the SRE, which can respond to signals generated by sis/PDGF, serum or phorbol esters, the SIF binding element mediates c‐fos induction only in response to sis/PDGF. The SRE and SIF elements function in an additive manner to stimulate the transcription of the c‐fos gene in response to sis/PDGF.

We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409–37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P ≤0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.

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The c-fos gene is rapidly and transiently activated in quiescent BALB/c-3T3 cells in response to serum, platelet-derived growth factor or conditioned medium from v-sis-transformed cells. This activation occurs at the level of transcription and in the absence of new protein synthesis. Using a gel electrophoresis DNA-binding assay, we have found a DNA-binding activity in BALB/c-3T3 cells that is induced within 20 min of treatment with conditioned medium from v-sis-transformed cells. A DNA methylation interference assay has shown that this factor binds to a sequence approximately 346 base pairs upstream of the transcription initiation site of the human c-fos gene. Insulin, epidermal growth factor, and phorbol 12-myristate 13-acetate fail to induce this DNAbinding factor. Protein synthesis inhibitors do not block the induction of this activity. We propose that this factor preexists in an inactive form in quiescent cells and that its binding activity is activated in response to appropriate extracellular inducers.