Human erythrocytes inhibit complement-mediated solubilization of immune complexes.

Incubation of precipitable immune complexes (IC) with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed human E were added to human serum or guinea pig serum, binding of IC to the E occurred and IC solubilization was significantly inhibited. By contrast, SRBC did not bind IC nor inhibit IC solubilization. Because IC binding to human E is mediated by CR type 1 (CR1) we evaluated whether CR1 was responsible for the inhibition of IC solubilization. Human E were treated with trypsin or anti-CR1 mAb. Both treatments abrogated IC binding to human E but did not affect the ability of the human E to inhibit IC solubilization. Human E inhibited C activation by IC. Thus, incubation of IC in human serum caused significant activation of C3 and C5, but not C4. However, when IC were incubated in whole blood or with isolated human E and serum, C3 activation by IC was inhibited significantly. In addition, we demonstrated that the C3b generated during C activation by IC deposited on both IC and human E. Thus, human E may compete for nascent C3 generated during C activation by IC. In conclusion, human E inhibit both complement-mediated solubilization of IC and C activation by IC.

Stabilization of poliovirus against heat inactivation.

Fatty acids and related compounds, as well as many salts, stabilize poliovirus against heat inactivation. Addition of myristate to poliovirus prevents heat-induced conformational changes which are detected by trypsin degradation of the virion. Using equilibrium dialysis, we found that several molecules of myristate bind per virion. The relative stabilizing potencies of the salts can be explained by the Hofmeister effect.

The role of returns to a prior topic in the negotiation of topic change: a developmental investigation.

Returns to a prior topic occurring in the conversations of small groups of acquainted peers were examined to learn more about how topic is organized in such settings and how it changes with age. Twenty-five discussion groups were formed, five at each of the following grades: second, fifth, ninth, twelfth, and college. The eighth meeting of each group was examined, comprising 13,811 speaking turns total, which includes 502 returns other than those occurring after side sequences. There are three main findings. First, at all ages, returns were frequently used to counter attempts at topic change. This finding warranted the creation of a model for the negotiation of topic change that includes returns. Second, there were no age differences in the means used for negotiating topic change, but there were substantial age differences in the way these means were actually employed. These differences suggest that adolescents and young adults adopt a consensual orientation to topic negotiation. Third, other results suggest that that consensual orientation to topic negotiation is a generalization of the consensus orientation to topic maintenance that is acquired during childhood.

Clearance of human antibody/DNA immune complexes and free DNA from the circulation of the nonhuman primate.

The present study evaluated the participation of the primate erythrocyte immune complex (IC) clearing mechanism in the clearance and organ uptake of double-stranded DNA (dsDNA) and of soluble ICs formed with human anti-DNA antibodies and dsDNA (dsDNA-ICs). Five baboons received 51Cr-labeled autologous erythrocytes and after a period of equilibration received separate intraarterial injections of [125I]free dsDNA and [125I]dsDNA-IC. Four of these five baboons were studied on a second occasion. To assess clearance from the arterial circulation and organ uptake, multiple blood samples were obtained from aorta, hepatic vein, and renal vein after injection of each probe. Two minutes after injection, a mean of 85% of dsDNA-ICs were bound to erythrocytes. By contrast, free dsDNA did not bind significantly to blood cells. The clearance rate of dsDNA-ICs from the arterial circulation was significantly faster than that of free dsDNA in all animals but one. Erythrocyte-bound dsDNA-ICs were cleared at a rate similar to that of total dsDNA-ICs. The liver was the major site of uptake of free dsDNA and of dsDNA-ICs. The hepatic uptakes of free dsDNA (17 +/- 8%/5 min) and dsDNA-ICs (27 +/- 8%/5 min) were not significantly different. 51Cr-labeled erythrocytes were not sequestered in the liver. There was not detectable uptake of free dsDNA or dsDNA-ICs by the kidney but with one exception. Thus, the primate erythrocyte IC clearing mechanism is involved in the clearance of dsDNA-ICs from the circulation but not in the clearance of free dsDNA.

Vasculature to the germinal matrix in rabbit pups.

The authors report a study of the cerebral vasculature of premature rabbits pertaining to the germinal matrix (GM). A pigmented silicone material (Microfil) was injected into the carotid artery of anesthetized rabbits. Methyl methacrylate vascular casts of a similar group of premature rabbits were examined by scanning electron microscopy. The GM is supplied by arteries from both the basal and convexity surfaces of the brain. Vessels could be identified as arteries or veins by their typical patterns of branching and by the characteristic impressions made on the methyl methacrylate casts by endothelial nuclei. Specific evidence of structural weaknesses in the vasculature, which could be a site of predilection for GM bleeding, was not observed. The similarities in basal ganglia vasculature between premature rabbits and humans justifies using the rabbit model to study vascular aspects of the GM and intraventricular hemorrhage.

The role of intracranial hypotension in neonatal intraventricular hemorrhage.

Most preterm infants develop transient intracranial hypotension, which reaches its lowest level on the 2nd day of life. This corresponds to the time when most neonatal intraventricular hemorrhage (IVH) occurs. In order to test the hypothesis that intracranial hypotension may have an etiological role in the development of IVH in premature infants, the authors induced intracranial hypotension in the preterm rabbit by the intraperitoneal injection of glycerol. The rabbit model is well suited for this study because this animal is at risk of developing spontaneous germinal matrix and ventricular hemorrhage. Compared to control littermates, the glycerol-treated animals exhibited a greater than 3.5-fold incidence of germinal matrix and intraventricular hemorrhage.

Changes in the water and electrolyte pattern of the brain and of the intracranial pressure during development in rabbits.

During its development the brain becomes dehydrated pari passu with growth and myelination and the electrolyte pattern changes from high sodium, low potassium to the opposite. The latter change is complete or virtually so in some species at term but in others the reversal is a postnatal occurrence. We have examined these features in rabbits of several ages and have measured the intracranial pressure at intervals during development as well. At or near both the water content of the brain is very high compared to that found later and the fetal electrolyte pattern is transitional in that the K/Na ratio is approximately one but not as high as in the mature brain. The intracranial pressure is lower in the newborn pups than it is later in development. Unlike that in mature animals the premature and young term rabbit brain is unable to affect ionic movements appropriate to the protection of the volume of the brain.