G-CSF control of neutrophils dynamics in the blood.

White blood cell neutrophil is a key component in the fast initial immune response against bacterial and fungal infections. Granulocyte colony stimulating factor (G-CSF) which is naturally produced in the body, is known to control the neutrophils production in the bone marrow and the neutrophils delivery into the blood. In oncological practice, G-CSF injections are widely used to treat neutropenia (dangerously low levels of neutrophils in the blood) and to prevent the infectious complications that often follow chemotherapy. However, the accurate dynamics of G-CSF neutrophil interaction has not been fully determined and no general scheme exists for an optimal G-CSF application in neutropenia. Here we develop a two-dimensional ordinary differential equation model for the G-CSF-neutrophil dynamics in the blood. The model is built axiomatically by first formally defining from the biology the expected properties of the model, and then deducing the dynamic behavior of the resulting system. The resulting model is structurally stable, and its dynamical features are independent of the precise form of the various rate functions. Choosing a specific form for these functions, three complementary parameter estimation procedures for one clinical (training) data set are utilized. The fully parameterized model (6 parameters) provides adequate predictions for several additional clinical data sets on time scales of several days. We briefly discuss the utility of this relatively simple and robust model in several clinical conditions.

The growth law of primary breast cancer as inferred from mammography screening trials data.

Despite considerable progress in understanding tumour development, the law of growth for human tumours is still a matter of some dispute. In this study, we used large-scale mammography screening trial data to deduce the growth law of primary breast cancer. We compared the empirical tumour population size distributions of primary breast cancer inferred from these data to the distributions that correspond to various possible theoretical growth functions. From this, we showed that the data are inconsistent with the exponential, logistic and Gompertz laws, but support power law growth (exponent approximately 0.5). This law indicates unbounded growth but with slowing mass-specific growth rate and doubling time. In the clinical size ranges, it implies a greater decline in the mass-specific growth rate than would be predicted by the Gompertz law using the accepted parameters. This suggests that large tumours would be less sensitive to cycle-specific therapies, and be better treated first by non-cell cycle-specific agents. We discussed the use of our study to estimate the sensitivity of mammography for the detection of small tumours. For example, we estimated that mammography is about 30% less sensitive in the detection of tumours in the 1 to 1.5-cm range than it is in detecting larger tumours.

Bromoalkane-degrading Pseudomonas strains.

Two Pseudomonas isolates, named ES-1 and ES-2, were shown to possess a wide degradative spectrum for haloalkanes in general and bromoalkanes in particular but did not degrade nonsubstituted alkanes. The utilization of water-insoluble haloalkanes, such as 1-bromooctane, appeared to consist of three phases: (i) extracellular emulsification by a constitutively excreted, broad-spectrum surface-active agent, (ii) dehalogenation by an inducible hydrolytic dehalogenase (possibly periplasmic), and (iii) intracellular degradation of the residual carbon skeleton. Several observations suggest the existence of more than one dehalogenase in strain ES-2.