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The structure of the copper protein plastocyanin from poplar leaves (Populus nigra var. italica) at 173 K has been subjected to two independent refinements, usin~ a single set of synchrotron X-ray data at 1.6 A resolution.Energy-restrained refinement using the program EREF resulted in lower root-mean-square deviations from ideal geom- Greater order in the solvent region is indicated by the location of 79 more solvent sites, the identification of extensive networks of hydrogen-bonded rings of solvent molecules, and a general decrease in the thermal parameters. Within the unit cell, the protein molecules are significantly translated and rotated from their positions at ambient temperature. An

This paper reports on the results of two controlled therapeutic trials on patients with endocrine tumours of the gastrointestinal tract. Seventeen patients were treated up to 18 months with recombinant interferona2c ( 2 x lo6 IU/m2 S.C. daily) and 16 pa-

A large difference in the number of gamma-IFN receptors was found on a variety of human tumor cell lines with a range of 0.4 to 15 X 10(3) binding sites/cell. The receptor number did not correlate with the potential responsiveness of the cells to gamma-IFN, in regard to either growth inhibition or induction of HLA-DR expression, two independently regulated gamma-IFN effects. However, with respect to HLA-DR expression it was found that the gamma-IFN sensitivity of inducible cell lines depended on the number of receptors, so that with increasing number of receptors present on these cells lower doses of gamma-IFN were required for induction of the gamma-IFN effect.

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Natural and recombinant interferons (IFNs) have already demonstrated therapeutic efficacy, including cytogenetic remissions, in patients with chronic myelocytic leukemia (CML). We investigated at the level of ligand-receptor interaction the question whether heterogeneity of receptor number or affinity might contribute to primary or secondary treatment failures in CML. We therefore analyzed IFN-gamma and IFN-alpha receptor expression and regulation during treatment with recombinant IFN-gamma and IFN-alpha in 15 patients with advanced CML. We found no difference in number or affinity of constitutively expressed IFN-gamma receptors (mean 1,100) and, on average, a 30% reduction of IFN-alpha receptors (mean 750) on peripheral blood mononuclear cells (PBMNC) of patients with chronic or accelerated CML as compared to mature granulocytes and/or bone marrow cells of healthy controls, which express on average 1,050 and 1,100 IFN-gamma and IFN-alpha receptors, respectively. While IFN-gamma receptor expression on PBMNC is not influenced upon treatment with rIFN-gamma, there is a substantial downregulation of IFN-alpha receptors in the course of rIFN-alpha therapy. Our data also show a differential pattern of receptor downregulation between patients achieving complete hematologic remission (CHR) (4 out of 12) compared with patients with partial hematologic remission (PHR) and non-responders. We conclude that differences in IFN receptor number cannot explain primary or secondary treatment failures. However, the differential ligand induced downregulation of IFN-alpha receptors in patients achieving CHR compared to those with PHR or non-responders suggest a prospective value of IFN-alpha receptor determination.

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