The concentration of the two principal drug-binding proteins, albumin and a,-acid glycoprotein, were measured in 44 paired fetal and maternal serum samples obtained at between 12 and 41 weeks gestation. Maternal serum albumin concentrations ranged between 25 and 35 g/1 during this period. Fetal serum albumin was much lower in early gestation, ranging from 7 . 5 to 16 g/1 at 12-15 weeks. With advancing age there was a linear increase so that at 30 weeks the fetal and the maternal serum albumin concentrations were in the same range and after 35 weeks the fetal concentrations exceeded the maternal by some 20%. Thus, the mean fetal/maternal serum concentration ratio of albumin increases from early pregnancy to term: 0.38 at 12-15 weeks; 0.66 at 16-25 weeks; 0.97 at 26-35 weeks; and 1.2 at >35 weeks gestation. Maternal serum a,-acid glycoprotein concentrations were scattered widely between 0.38 and 1.05 g/l. With the technique used fetal serum concentrations were hardly detectable before 16 weeks. Thereafter they increased at a constant rate, but never attained the maternal values. Near term a fetal/maternal serum concentration ratio of 0.37 was reached. These changes in protein concentrations may have important pharmacological implications.

We have evaluated 3,620 bone marrow aspirates from 2,877 patients with solid tumors for the presence of clinically unsuspected metastasis. All aspirates were obtained from the iliac crest as part of the prechemotherapy workup and processed as smear and paraffin sections of the clot. Of the 2,877 patients, 263 (9.1%) showed metastatic tumor. Of these, metastasis was most frequent in neuroblastoma (48.2%), Ewing's sarcoma (35.5%), oat cell carcinoma (20.7%), prostate carcinoma (20.3%), breast carcinoma (19.6%), squamous cell carcinoma of the lung (15.7%), rhabdomyosarcoma (16.2%), and melanoma (6.8%). In most instances (92%), tumor cells were demonstrated simultaneously on both smears and clot sections. However, in lung and breast carcinoma, metastasis was noted more frequently in clot sections, while smears were superior for detecting both neuroblastoma and rhabdomyosarcoma. The prognostic significance of bone marrow involvement in 83 patients with state IV malignant melanoma scheduled for immunochemotherapy was investigated. In 39 patients (Group B, no bone marrow infiltration), the median survival was 59 weeks. In 44 patients (Group A, infiltrated bone marrow), the median survival was 6 weeks. Although bone marrow metastasis did not preclude response to immuno,chemotherapy, after 40 weeks only two patients of Group A were still alive, compared to 16 in Group B. This study demonstrates the usefulness of combining clot section and smear examinations for increased detection of unsuspected bone marrow metastasis and suggests the prognostic significance of bone marrow involvement in malignant melanoma.

Lymphocytes are primordial immune cells with variable life times. Besides genetic programming, extracellular factors interacting with cell surface receptors might alter cell survival. We investigated whether the activity of the membrane-embedded Na,K-ATPase (EC3.6.1.37) or sodium pump (NKA) plays a role for cell survival since this ubiquitous system establishes the vital transmembrane Na and K gradients as well as the resulting high intracellular K/Na ratio required for macromolecule synthesis; furthermore, the system exposes an extracellular inhibitory receptors for cardioactive steroids and palytoxin. Isolated human lymphocytes were incubated in vitro and their viability assessed by exclusion of trypan blue. Various incubation conditions were compared; in RPMI-1640 medium cell viability was preserved for 30 h at 37 degrees C. Externally added ouabain, a hydrophilic cardioactive steroid, blocked the [86Rb]potassium uptake at nanomolar concentrations. Despite pump inhibition ouabain did not alter lymphocyte survival, even at 10 mM for 30 h. By contrast, the hydrophilic toxin palytoxin, the most potent animal poison described so far, killed all cells within 2 h at 10 nM; this toxin is known to act via the sodium pump and to provoke deadly cation-leaks by unmasking a channel component. Intracellular Na increased and K decreased as measured by atomic absorption spectrometry in presence of palytoxin; cell swelling was seen by electron microscopy. Ouabain protected the cells from the toxic effect of palytoxin. The results reveal a pivotal role of NKA integrity for lymphocyte survival.

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