Interleukin-4 (IL-4) has important regulatory functions in the immune system, particularly in the generation of immunoglobulin E, the principal mediator of allergic responses. The molecular basis of IL-4 action has remained elusive so far. Here we report on a novel human transcription factor, termed nuclear factor IL-4 (NF-IL4), which is posttranslationally activated by IL-4 in lymphoid and monocytic cells. Homologous binding sequences for NF-IL4 were identified in the promoter regions of the IL-4 controlled CD23b and I epsilon genes. We defined a palindromic 9-bp consensus sequence (5'-TYCYRRGAA-3') as IL-4-responsive element (IL-4RE). Point mutation analysis of the CD23b promoter showed that binding of NF-IL4 to the IL-4RE is essential for the initiation of gene transcription in response to IL-4. NF-IL4 was not activated by Ca2+ ionophore, phorbol ester and cAMP either alone or in combination suggesting a non classical pathway for IL-4 signal transduction.

To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.000~).Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases. Cancer 68:574-582,1991. Accepted for publication December I I , 1990. recognized first for colorectal carcinomas and then for solid tumors in generaL4 By contrast, the unraveling of the molecular structure of this tumor antigen not only did not progress but was even delayed as, in time, it became evident that there was no single CEA but rather a large family of more or less closely related glycoproteins. There is a general consensus now concerning the main properties of CEA.' These are its: beta electrophoretic mobility, solubility in perchlonc acid, molecular weight of 180,000 k 20,000 Daltons, absence of methionine, and single-polypeptide properties. Considering the low sensitivity of CEA in the early stages of breast cancer (6% to 18% depending on the cutoff value), this tumor marker is not suitable for ~creening.~-~ Several studies showed a correlation of CEA values with tumor size and mass and with the presence of lymph nodes or far metastases in breast cancer.6 The major utility of CEA lies in follow-up examinations for tumors." It is elevated in only one third of the cases with demonstrable 5 74

The effects of interleukin-13 (IL-13) and interleukin-4 (IL-4) on cellular functions were shown to be quite similar. We provide evidence that in monocytes as well as in T lymnhocytes both IL-4 and IL-13 activate the same recentlv identified transcrintion factor NF-IL4 which binds to the specific responsive element IG4RE. In addition, we show that a nuclear factor activated by interferon-y also interacts with the IL-4RE. It differs from NkIL4 in the electrophoretic mobility of the complex with DNA, in its DNA-binding speciticity and in the proteins interacting with the DNA sequence. Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines.

Background: ICAM-1 is known to be strongly expressed on keratinocytes in lesional atopic eczema correlating with the degree of inflammation. ELAM-1 was found to be expressed on dermal vascular endothelium in lesional atopic eczematous skin. Objective: The present study was performed to investigate whether elevated serum levels of soluble forms of these molecules are detectable in patients with severe atopic eczema and whether these parameters could be useful markers for disease activity. Methods: Serum levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1) were measured by ELISA in 18 patients with severe atopic eczema before and after UVA1 therapy. Results: Before onset of treatment, serum sICAM-1 (565 + 99 ng/ml) and sELAM-1 (89.7 ± 29.9 ng/ml) levels were significantly (p < 0.001) elevated compared to 22 healthy control persons (296 ± 46 and 48.8 ± 22.7 ng/ml). After achievement of significant clinical improvement after 3 weeks of UVA1 therapy, there was neither a decrease in serum sICAM-1 nor in sELAM-1 levels. The posttherapeutic serum sICAM-1 and sELAM-1 values remained elevated (p < 0.001) above the normal range. Conclusion: Based on these data we suggest that (1) serum sICAM-1 and sELAM-1 are elevated in patients with severe atopic eczema, (2) sICAM-1 does not decrease together with reduction of ICAM-1-positive keratinocytes in atopic eczema following clinical improvement and might therefore be mainly of a different origin, i.e. leukocytes/endothelial cells, and that (3) sICAM-1 and sELAM-1 seem not to be suitable markers of actual disease activity in severe atopic eczema.

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.