The cotton rat: an underutilized animal model for human infectious diseases can now be exploited using specific reagents to cytokines, chemokines, and interferons.

The cotton rat represents the best or only animal model for a large number of human infectious diseases, and it may be unique among small laboratory animals in its susceptibility to several potential agents of bioterrorism. Although the cotton rat is a reliable model to define pathologic changes produced during infection with human pathogens, the lack of specific reagents has precluded a more extensive analysis of the molecular basis of pathogenesis. Here, we report the cloning of 24 cotton rat genes encoding various cytokines, chemokines, and interferons (IFNs). Analysis of the expression of most of these genes was performed by RT-PCR in cotton rat macrophages during treatment with lipopolysaccharide (LPS) and in cotton rat lungs after infection with influenza virus. The availability of these reagents will provide the tools for molecular analysis of pathogenesis and immune responses to a wide variety of pathogens and set the basis for the development of new prophylactic and therapeutic strategies against human infectious diseases.     

Changes of plasma volume and plasma composition in water-deprived rats

Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.     

Failure of averaging in the construction of a conductance-based neuron model

Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.     

The effect of amiloride on sodium and potassium fluxes in red cells

1. The effect of amiloride on the influx and efflux of (24)Na and (42)K in red cells was studied. The drug was added to the bathing Ringer or else incorporated in resealed ghosts.2. Amiloride does not inhibit the active or the passive (ouabain insensitive) extrusion of (24)Na.3. Amiloride inhibits the influx of (24)Na into red cells by 70%.4. Whether added to the inside or to the outside of the cells amiloride has no effect on the efflux of (42)K.5. Amiloride does not modify the uptake of (42)K from control Ringer. This uptake is strongly inhibited by the removal of Na. Amiloride has no effect on the extent of this inhibition.6. It is concluded that amiloride specifically inhibits the passive penetration of Na, and has no effect on the Na-K-pumping mechanism. However, at the concentration which inhibits 70% of the influx, amiloride fails to produce an observable effect on the ouabain-insensitive Na-efflux.7. On the basis that the information obtained could be extrapolated to other membranes, the effect of amiloride on epithelial membranes is discussed.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).