Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.0% of the cases HER-2/neu was overexpressed, and in 46.7% the p53 protein level was increased. Expression of these two oncogene products was closely correlated. Overexpression of both oncogenes was associated with larger tumour size and negative hormone receptor. The percentage of HER-2/neu and p53 overexpression was higher in node-positive patients, although statistical evaluation was not significant. While overexpression of HER-2/neu as well as p53 in node-positive patients was associated insignificantly with shorter disease-free survival, a significant difference could be documented when the disease-free survival of patients with overexpression of both oncogene proteins was compared to that of patients with no overexpression.

No abstract

The aim of the present study was to test simple reaction sequences which describe calcium-independent plus calcium-dependent phosphorylation of sarcoplasmic reticulum transport ATPase by orthophosphate including the function of magnesium in phosphoenzyme formation. The reaction schemes considered were based on the reaction sequence for calcium-independent phosphorylation proposed previously; namely that the transport enzyme (E) forms a ternary complex (Mg . E . P,), by random binding of free magnesium and free orthophosphate, which is in equilibrium with the magnesium-phosphoenzyme (Mg . E-P).Phosphorylation, performed at pH 7.0 20 "C and a constant free orthophosphate concentration using sarcoplasmic reticulum vesicles either unloaded or loaded passively with calcium in the presence of 5 mM or 40 mM CaCI2, resulted in a gradual decrease in the apparent magnesium half-saturation constant and an increase in maximum phosphoprotein formation with increasing calcium loads. When phosphorylation of sarcoplasmic reticulum vesicles preloaded in the presence of 5 mM CaC12 was performed at a constant free magnesium concentration, a decrease in the apparent orthophosphate half-saturation constant and an increase in maximum phosphoprotein formation was observed as compared with vesicles from which calcium inside has been removed by ionophore X-537A plus EGTA treatment ; however, both parameters remained unchanged by increasing free magnesium from 20 mM to 30 mM. When phosphorylation of sarcoplasmic reticulum vesicles passively loaded with calcium in the presence of 40 mM CaC12, at which the saturation of the low-affinity calcium binding sites of the ATPase is presumably near maximum, was performed at increasing concentrations of free orthophosphate, there was a parallel shift of phosphoprotein formation as a function of free magnesium and vice versa, with no change in the maximum phosphoenzyme formation.Comparison of the experimental data with the pattern of phosphoprotein formation predicted from model equations for various theoretical possible reaction sequences suggests that phosphoenzyme formation from orthophosphate possesses the following features. Firstly, calcium present at the inside of the sarcoplasmic reticulum membrane binds to the free enzyme and in sequential order to E . Mg . P, or Mg . E-P or to both, but neither to E . Mg nor to E . P,. Secondly, calcium-independent and calcium-dependent phosphoproteins are magnesium-phosphoenzymes. Calcium-dependent phosphoenzyme is a magnesium-calcium-enzyme phosphate complex with 1 magnesium, 2 calciums and 1 orthophosphate (the last covalently) bound to the enzyme [Mg . E-P . (Cai)z], and not a 'calcium-phosphoprotein' without bound magnesium.Phosphorylation of sarcoplasmic reticulum ATPase from orthophosphate is part of the reversal of the calcium pump of skeletal muscle [I -31 and cardiac muscle [4,5] sarcoplasmic reticulum [ 61. Studies on phosphorylation of sarcoplasmic reticulum ATPase from orthophosphate may contribute to a better understanding of the intermediate...

Serum concentrations of acute-phase-proteins C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha 1-acid glycoprotein (AGP) as well as levels of immunoglobulins G, A and M and of complement components C3 and C4 were evaluated in 15 patients with advanced (stages III and IV) Hodgkin's disease. Of these patients 9 suffered from B symptoms including pruritus, night sweats and fever. While all patients had highly increased concentrations of CRP and AAT and 11 patients also had elevated levels of AGP in their sera, these concentrations were significantly (P less than 0.001) reducible by the administration of chemotherapy. Patients with B symptoms also had significantly higher concentrations of CRP (P less than 0.02), AAT (P less than 0.05) and AGP (P less than 0.05) in their sera than patients without. Plasmapheresis which was performed in 3 patients did not achieve a long-lasting reduction of serum concentrations of any acute-phase-protein tested. Complement components C3 and C4 exhibited a similar behaviour as acute-phase-proteins in that they were elevated in patients with B symptoms and reducible by the administration of chemotherapy (P less than 0.001 and P less than 0.02, respectively). We conclude that serum concentrations of CRP, AAT and AGP can serve as useful markers for the assessment of tumour activity in patients with advanced Hodgkin's disease. Whereas the concentrations of immunoglobulins G and A in patients were comparable to normal controls, IgM was significantly (P less than 0.05) reduced in patients who had received chemotherapy, but not in those who were newly diagnosed and had not received any treatment. Thus, chemotherapy lowered serum concentrations of IgM without influencing levels of IgG and IgA.

The gender-specific prevalence of lymphangioleiomyomatosis (LAM) in premenopausal women suggests a hormonal etiology. Despite the antiestrogenic treatment (ovariectomy, tamoxifen) this disease is often refractory to therapy and almost inevitably leads to the patient's death. We describe a case where the antiproliferative effect of systemically applied interferon alpha 2b was successfully employed in addition to ovariectomy and the patient reached complete remission.