Transformation During Mixed Pneumococcal Infection of Mice

The recent demonstration by others of transformation during peritoneal infection of mice by two genetically distinct pneumococcal strains supports the notion that transformation may be significant in pneumococcal infection in nature. These studies confirm the occurrence of transformation during mixed infection of mice and define some conditions for its occurrence and its significance. Mice were inoculated with deoxyribonucleic acid (DNA) donor (small type III capsule, low virulence, streptomycin-susceptible) and recipient (noncapsulated, low virulence, streptomycin-resistant) pneumococci, and the bacteremia in mice that died was evaluated. Transformants (large type III capsule, virulent, streptomycin-resistant) were isolated from up to 80% of mice that died from mixed peritoneal infection. Transformation occurred in mice that received donor and recipient 6 hr apart; hence, active DNA was released and competence developed during growth in vivo. Transformation was detected only with progressive infection by both strains, and then transformants were few in the blood and apparently were not responsible for the death of the animals. In doubly infected mice treated with streptomycin, transformation was enhanced; transformants numerically dominated the bacteremia and seemed to cause the death of the mice. Transformation was also demonstrated for the first time during infection of the respiratory tract.     

Liver nucleotides in acute experimental liver injury induced by dimethylnitrosamine and by thioacetamide

1. The concentrations of the nicotinamide-adenine dinucleotides in rat liver have been determined at intervals during the period 1-24hr. after feeding adult female rats with dimethylnitrosamine or thioacetamide. 2. The administration of dimethylnitrosamine resulted in a rapid decrease in the sum of NAD+NADH(2). This sum was decreased by 40% 3hr. after dosing. 3. Dimethylnitrosamine administration also produced an overall decrease in the NADP+NADPH(2) but this decrease was not so early nor as marked as that found for NAD+NADH(2). 4. The changes produced by thioacetamide were quite different from those obtained with dimethylnitrosamine. Thioacetamide produced a temporary rise in the NAD+NADH(2) followed by a small fall. The NADP+NADPH(2) was little changed in the early hours after dosing with thioacetamide but had decreased by approx. 15% 18hr. after administration. 5. These changes are discussed in terms of the known hepatotoxic actions of dimethylnitrosamine and thioacetamide, and are compared with previously reported changes found after the administration of carbon tetrachloride.     

Measurement of Streaming Potentials of Mammalian Blood Vessels, Aorta and Vena Cava, in Vivo

Attempts to measure streaming potentials in large rabbit blood vessels in vivo have been carried out. Streaming potentials, V(89), were measured by the introduction of microelectrodes through the wall of the blood vessel at separations greater than 1 cm. The outputs from these electrodes fed through calomel cells were amplified and recorded directly by using an Electronics for Medicine photorecorder (White Plains, N. Y.). "Effective streaming currents" were determined by running the output through a low impedence galvanometer while simultaneously measuring the resistance of the circuit V(8) were, therefore, calculated from two measurements and compared. Flow through vessels studied was measured using two different electromagnetic flowmeters. The results indicate that V(8) present in both aorta and vena cava are of the order of 5 to 10 mv. By using the Helmholtz-Smoluchowski equation into which flow was reintegrated, the numbers yield zeta potentials approximating 0.1 to 0.4 v in both aorta and vena cava. This number approaches the apparent upper limit for zeta (actually "interfacial potentials") potentials in biological systems. The measured "i.f." potential is considered as the interreaction of several physical and metabolic factors operating at the blood intimal interface. The polarity of the potential suggests that the interface is negative with respect to the blood flowing through the vessel. Interfacial potential and related V(8) are discussed in terms of their possible importance as a mechanism for maintaining vascular homeostasis in the living animal.     

Decreased rotational diffusion of band 3 in melanesian ovalocytes from Papua,New Guinea

Summary Melanesian ovalocytes from Papua New Guinea have an N-terminal extension of the band 3 polypeptide (Jones, G.L., Edmunson. H.M., Wesche, D., Saul, A. 1990.Biochim. Biophys. Acta 1096:33–40). The ovalocytes showed a threefold increase in shear elastic modulus as determined by micropipette aspiration measurements of membrane rigidity. Time-resolved phosphorescence anisotropy has been used to study the rotational freedom of band 3 in membranes prepared from ovalocytes. The ovalocytic polymorphism was found to be associated with a marked decrease in the rotational mobility of band 3. This may indicate participation of band 3 in large homoaggregates or in complexes with other proteins at the cytoplasmic surface. There was no morphological clustering of band 3 detectable by immunofluorescence microscopy.     

Erythropoietin stimulates 45Ca2+ uptake in Friend virus-infected erythroid cells

It has been shown previously in this laboratory that in vitro infection of mouse bone marrow cells with the anemia strain of Friend leukemia virus leads to growth of large bursts of erythroid cells which are arrested in development prior to hemoglobin synthesis but can respond to erythropoietin (EP) to complete the late stage of erythroblast differentiation. In this study, the effect of EP on the metabolism of 45Ca2+ in these cells was examined. At 4 degrees C, an increased rate of 45Ca2+ uptake and efflux as well as an increase in the steady state level of 45Ca2+ in treated cells was observed. Exchange of 45Ca2+ from preloaded cells at 4 degrees C indicated that treatment with EP increased the size of a rapidly exchanging pool of 45Ca2+ from 5 to 12% of total 45Ca2+ in the cell. The effect of treatment with EP can be seen as increased exchange of extracellular 45Ca2+ with cellular Ca2+; however, an effect of EP on the net level of Ca2+ in these cells cannot be excluded. This investigation demonstrates one of the earliest effects of EP on erythroid cells and suggests that alterations in Ca2+ metabolism may contribute to the progression of erythroid cells to their final development.     

The development of vasopressin antagonists

Antagonists of the physiological actions of vasopressin can be useful probes for detecting the influences of endogenous vasopressin on cardiovascular regulation. Antagonists that block vascular receptors of the V1 type have been widely used for this purpose. Recently effective antagonists of renal antidiuretic receptors of the V2 type have become available, and we have made progress toward improving their specificity for V2 receptors. Vasopressin antagonists of both types of responses could become useful in the diagnosis and treatment of pathophysiological states in which elevated levels of circulating vasopressin may disturb cardiovascular and renal functions.