Chronochemotherapy: L 1210 leukemia and beyond

In cancer and other therapeutic research, an interpretation of median survival times can and should take cure into account. With this qualification, an analysis of recently published data provides further statistically significant evidence in favor of cancer chronotherapy as compared to homeostatic therapy.     

Cyclic AMP-dependent protein kinases of Paramecium. II. Catalytic and regulatory properties of type II kinase from cilia

The type II cAMP-dependent protein kinase (cAMP-PK-II) from cilia of Paramecium, purified free of type I cAMP-PK (cAMP-PK-I) and of cGMP-dependent protein kinase (cGMP-PK), phosphorylated several basic proteins and a heptapeptide containing serine (Kemptide). The enzyme was partially inhibited by the protein kinase inhibitor (Walsh inhibitor), but only at relatively high inhibitor concentrations. Half-maximal activation of cAMP-PK-II occurred at 15-25 nM cAMP. Several cAMP analogs were tested for ability to bind and activate the enzyme. 8-bromo-cGMP, a potent activator of Paramecium cGMP-PK, was a poor activator of Paramecium cAMP-PK-II. Activation of cAMP-PK-II was influenced by the phosphorylation assay buffer. Phosphate buffers provided increased activation by cAMP but decreased total activity relative to that measured in Mops-Tris buffer. The kinase was cAMP-independent when the pH of the assay buffer was high. Preincubation of cAMP-PK-II with histones also activated the enzyme in the absence of cAMP. The cAMP-PK-II bound cAMP with a Kd of 23 nM, and bound cAMP was released with a biphasic time course, suggesting two non-identical binding sites. The properties of the cAMP-PK of this ciliated protozoan appear to be closely similar to those of vertebrates.     

CHARACTERIZATION OF DEVELOPMENT IN MAIZE THROUGH THE USE OF MUTANTS. I. THE POLYTYPIC (Pt) AND RAMOSA-1 (ra1) MUTANTS

The origin of morphological differences attributable to mutant genes can be identified at certain switch points in the developmental pathway. The effect of the Polytypic (Pt) gene is a stimulus to meristems in the developing inflorescence to continuous initiation of differentiating structures. The most severe expression is a suppression of meristematic activity. The action of the gene is a superimposition of its effect on the normal developmental pathway. The ramosa-1 (ra₁) gene interrupts the normal sequence of events, at the switch point, which would normally result in spikelet formation, and there is produced instead a lateral branch. The response of numerous switch points in the developmental pathway of the maize inflorescence supports the conclusion that meristems are a plastic system genetically programmed at successive intervals.