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The amino acid sequence of porcine relaxin is distinctly similar to that of insulin, particularly in regard to the placement of the cystine residues, suggesting the likelihood of three-dimensional homology as well. Two computer-modeling studies have produced structures consistent with this possibility. While the overall correctness of these predictions can only be adequately tested by x-ray crystallographic analyses, solution methods can determine if the placement of certain side chains is compatible. By use of charge transfer titrations, the solvent availability of the two tryptophan residues located in the B chain has been examined. N-Methylnicotinamide chloride forms weak complexes with indole moieties that are readily detected by visible absorption measurements. Such reactions occur in proteins if the tryptophan residues are fully exposed which was found to be the case in relaxin. Furthermore, Trp B-18 was also fully available, by this criterion, when the Trp-Gly-Arg sequence was removed from the carboxyl terminus of the B chain by carboxypeptidase Y. These results clearly favor only one of the predicted orientations of Trp B-18 and suggest an altered position of the carboxyl terminal region of the B chain than that previously proposed.

One of the principal mechanisms for the control of blood coagulation in man is the interaction of serum inhibitors with proteolytically active clotting factors, with concomitant losses in thrombogenic activity. One of the inhibitors, antithrombin III, which migrates as an α2-globulin on gel electrophoresis (1, 9, 13, 20), has received considerable attention. It appears to be identical with heparin cofactor and factor xa inhibitor (21) and provides the major site of action of heparin in inhibiting thrombin formation. However, it should be noted that the inhibition of thrombin is not limited to antithrombin III. Two other plasma proteins, an α2- macroglobulin (1, 3, 4, 11, 17), and the a α1,-proteolytic inhibitor (2, 14, 17) also show such activity. The latter inhibitor is probably identical with α1-antitrypsin (14), the protein responsible for most of the inhibition of trypsin activity in human serum.

Investigations in a variety of systems have shown that dissociated single cells will, under appropriate conditions, aggregate and, if maintained in culture, will morphologically differentiate to resemble the original organ or tissue (23, 33, 34). It can further be shown that in mixed aggregates of cells prepared from different organs (for example, neural retina and liver) there occurs cell segregation such that cells originally derived from the same organ attached to each other and separate from the cells derived from a different organ. The simplest explanation for this observation is that cells have a preferential or higher affinity for homologous cells, and if free to move within the aggregate, will rearrange so as to be adjacent to homologous rather than hetero-logous cells. This simple view is probably an oversimplification, because not only do cells migrate to be adjacent to homologous cells, but they also take up characteristic positions within the aggregate which cannot be explained simply by differential affinities (33).

Nerve growth factor (NGF), a substance which regulates the growth and viability of sympathetic and certain sensory neurons in a hormonelike manner (Levi-Montalcini and Angeletti, 1968; Bradshaw et al., 1976), has been identified in a wide variety of tissue sources (Levi-Montalcini, et al., 1954; Bueker et al., 1960; Angeletti and Vignetti, 1971; Young et al., 1976), and isolated in homogeneous form from a number of them (Varon et al., 1967; Bocchini and Angeletti, 1969; Angeletti, 1968, 1970; Pearce et al., 1972). Historically, it was first observed in sarcomas 37 and 180 (Bueker, 1948; Levi-Montalcini, 1952; Levi-Montalcini and Hamburger, 1953) and, although substantially purified (Cohen et al., 1954), it was never obtained in a homogeneous form from this source. However, these experiments led to the discovery that poisonous snakes (Crotalidae, Elapidae, and Viperidae) and, most importantly, the adult male mouse submandibular gland were much richer sources of NGF (Cohen and Levi-Montalcini, 1956; Cohen, 1960).

During the more than twenty years since its discovery (11), the nerve growth factor (NGF) has been indeed demonstrated to be an essential protagonist in the growth and development of the sympathetic nervous system (12). The NGF-stimulated growth response has been amply described from both metabolic and ultrastructural viewpoints.