Optimal systems: I. The vascular system

An approach to quantitative work on optimal systems is considered. Desired optimal principles are utilized in constructing a hypothetical system similar to the organ system considered. A comparison of this constructed system with the anatomical system then gives an indication of the importance of the optimal principles in the form or function of the organ system considered. These ideas are applied to the mammalian vascular system, and limiting values are obtained for some of its important component parts. The constructed system gives good agreement with anatomical data for vessel radii, lengths, and hydrodynamic resistance to flow.     

The T-cell receptor mediating restrictive recognition of antigen

Four facts characterize restrictive recognition of antigen. First, in large measure, allele-specific determinants on R are recognized when R is functioning either as a restricting element (RL) or as an allo-target (or even xeno-target) (RF). Second, there is a high frequency of virgin antigen-responsive t cells with alloreactivity, i.e. anti-RF. Third, there is a strict relationship between the class of effector function and the class of RL recognized (restrictive recognition of antigen, XF) but a relaxed relationship between class of effector function and class of RF recognized (alloreactivity). Fourth, the effector T cell functions anti-RL-dependently when XF is the target (restrictive recognition of antigen) and anti-RL-independently when RF is the target (alloreactivity). From these facts are derived the following conclusions. The T cell uses a dual recognitive, single receptor (Model I, Figure 1). A single germ-line VT locus specifying anti-allele-specific recognition of species R encodes both the anti-R and the anti-X combining sites. A "learning" process (occurring in the thymus) is required to establish the restriction specificity (anti-RL) as well as the effector function/class of RL relationship. The repertoire is derived by somatic mutation of all germ-line VT genes specifying anti-RF (Model IA, Table 3 and Figure 9). Given Model IA (Table 3 and Figure 9), we can account further for the existence of an extensive polymorphism of R and minimal polygeneism, for the high frequency of crossreactivity between anti-XF and RF, and for the physiology and genetics of cell-cell communication in immune responsiveness.     

Nucleotide sequence analysis of Aleutian mink disease parvovirus shows that multiple virus types are present in infected mink.

Different isolates of Aleutian mink disease parvovirus (ADV) were cloned and nucleotide sequenced. Analysis of individual clones from two in vivo-derived isolates of high virulence indicated that more than one type of ADV DNA were present in each of these isolates. Analysis of several clones from two preparations of a cell culture-adapted isolate of low virulence showed the presence of only one type of ADV DNA. We also describe the nucleotide sequence from map units 44 to 88 of a new type of ADV DNA. The new type of ADV DNA is compared with the previously published ADV sequences, to which it shows 95% homology. These findings indicate that ADV, a single-stranded DNA virus, has a considerable degree of variability and that several virus types can be present simultaneously in an infected animal.     

Bacterial lipopolysaccharide regulates the phosphorylation of the 68K protein kinase C substrate in macrophages

Bacterial lipopolysaccharide (LPS) potentiates protein kinase C (PKC)-dependent responses such as the activation of arachidonic acid metabolism in macrophages (Aderem, A. A., Cohen, D. S., Wright, S. D., and Cohn, Z. A. (1986) J. Exp. Med. 164, 165-179). Concomitantly, LPS promotes the myristoylation of a 68K PKC substrate, shown to be equivalent to the 80/87K PKC substrate found in brain and fibroblasts (Aderem, A. A., Albert, K. A., Keum, M. M., Wang, J. K., Greengard, P., and Cohn, Z. A. (1988) Nature 332, 362-364). We have now examined the effect of LPS on the phosphorylation of this 68K PKC substrate. We report here that LPS modifies the kinetics and extent of phosphorylation of the 68K protein. While treatment with LPS alone induces low level phosphorylation of the 68K protein, it markedly increases the rate of subsequent phorbol 12-myristate 13-acetate (PMA)-dependent phosphorylation of this protein. Phosphorylation in LPS-treated macrophages was maximal 1-2 min after administration of PMA, while maximal phosphorylation in macrophages not exposed to LPS was only achieved 6 min after addition of PMA. In addition to increasing the rate of PMA-dependent phosphorylation of the 68K protein in macrophages, LPS also promoted the phosphorylation of a novel peptide on the 68K protein. Thus while PMA stimulated the phosphorylation of two thermolytic phosphopeptides (phosphopeptides 1 and 2), the low level of phosphorylation observed with LPS alone was found to occur on phosphopeptides 1 and 2 as well as on a novel phosphopeptide (phosphopeptide 3). Furthermore, LPS treatment of macrophages potentiated phosphorylation of all three phosphopeptides when the cells were subsequently stimulated with PMA. While phosphorylation stimulated by LPS and PMA was slightly more than additive for phosphopeptides 1 and 2, it was markedly synergistic (increased 14.5-fold) for phosphopeptide 3. Phosphorylation of all three phosphopeptides occurred exclusively on serine. It is possible that LPS-induced myristoylation of the 68K protein directs it to the membrane where its phosphorylation is enhanced by its close association with PKC.