Regulation of IgE antibody production by serum molecules. IV. Complete Freund's adjuvant induces both enhancing and suppressive activities detectable in the serum of low and high responder mice.

Two biologically active serum molecules manifesting precisely opposite biologic effects, both of which are selective for IgE antibody synthesis, can be detected in the serum and ascites fluids of CFA-immune mice. One activity, described previously, is suppressive and hence termed suppressive factor of allergy (SFA); the other, reported for the first time herein, is enhancing and has been termed enhancing factor of allergy (EFA). The ability to detect one vs the other activity requires certain special manipulations such as different doses of low dose x-irradiation. Conclusive evidence for the existence of two distinct factors mediating these two opposing biologic effects was obtained in studies demonstrating that affinity chromatography on concanavalin A-Sepharose segregated the two molecular entities. Thus, SFA binds poorly or not at all to Con A-Sepharose, whereas EFA binds to Con A and can be recovered in the eluate eluted with the competitive sugar alpha-methyl-D-glucopyranoside.     

Adaptive differentiation of murine lymphocytes. III. T and B lymphocytes display reciprocal preference for one another to develop optimal interacting partner cell sets.

Responses to the synthetic terpolymer L-glutanmic acid, L-lysine, L-phenylalanine (GLphi) and hapten derivatives thereof are controlled by two complementing H-2 linked Ir genes in the mouse. F1 hybrids derived from two different nonresponder strains (one of which possesses the alpha and the other beta Ir-GLphi gene) are phenotypic responders to GLphi and 2,4-dinitrophenyl (DNP)-GLphi. Moreover, spleen cells from DNP-GLphi-primed F1 mice can adoptively transfer secondary anti-DNP antibody responses to irradiate been challenged with DNP-GLphi. When, however, GLphi-primed F1 helper T cells are transfered together with the DNP-specific F1 B cells that had been primed in separate mice altogether by DNP coupled to an unrelated protein carrier, such mixtures failed to develop adequate adoptive secondary anti-DNP responses to DNP-GLphi. This contrasted with the ability of the same GLphi-primed F1 T cells to provide helper activity for DNP-primed B cells from responder recombinant B10.A (5R) mice. More important, the apparent defect of GLphi-primed F1 T cells in providing help for DNP-primed F1 B cells (primed to a DNP-protein conjugate) could be readily overcome by using DNP-primed B cells from donor F1 mice primed with DNP-GLphi. As discussed herein, these results suggest that interacting T and B lymphocytes pair off into partner cell sets, any pair of which interact optimally when a "best fit" reciprocal self-recognition occurs between them.     

The effect of calmodulin on the phosphoprotein intermediate of Mg2+-dependent Ca2+-stimulated adenosine triphosphatase in human erythrocyte membranes.

The effect of calmodulin on the formation and decomposition of the Ca2+-dependent phosphoprotein intermediate of the (Mg2+ + Ca2+)-dependent ATPase in erythrocyte membranes was investigated. In the presence of 60 microM-Ca2+ and 25 microM-MgCl2, calmodulin (0.5-1.5 microgram) did not alter the steady-state concentration of the phosphoprotein, but increased its rate of decomposition. Higher calmodulin concentrations significantly decreased the steady-state concentration of phosphoprotein. Calmodulin (0.5-1.7 microgram) increased Ca2+-transport ATPase activity by increasing the turnover rate of its phosphoprotein intermediate. Increasing the MgCl2 concentration from 25 microM to 250 microM increased the (Mg2+ + Ca2+)-dependent ATPase activity, but decreased the concentration of the phosphoprotein intermediate. Similarly to calmodulin, MgCl2 increased the turnover rate of the Ca2+-transport ATPase complex (about 3-fold). At the higher MgCl2 concentration calmodulin did not further affect the decomposition of the phosphoprotein intermediate. It was concluded that both calmodulin and MgCl2 increase the turnover of the Ca2+-pump by enhancing the decomposition of the Ca2+-dependent phosphoprotein intermediate.     

Circadian rhythms in juvenile american shad, Alosa sapidissima

Swimming activity (in cm s⁻¹) of a school (55 individuals) of young-of-the-year ( total length=110 mm) American shad, Alosa sapidissima , was determined under a variety of photoperiod conditions. These included a normal (ambient), a shifted, and constant-light day. Swimming activity was measured over 4-day periods. During normal days swimming speeds followed periods of about 24 h, with fast speeds (up to 45 cm s⁻¹) and schooling occurring during the photoperiod. Under dark conditions speeds were slower (8 cm s⁻¹) with most fish swimming as individuals. During a shifted day swimming speeds and schooling corresponded to the imposed day. Under constant light (equivalent to bright moonlight) no schooling was evident, and a constant, but slow, swimming speed was observed in each 24-h period. These shad demonstrated an exogenous rhythm with respect to the imposed day length. It is hypothesized that an endogenous circadian rhythm would only be of use to a fish required to hunt or chase its prey. Shad, being plankton feeders, do not chase prey and therefore can exhibit an exogenous circadian rhythm with no detrimental feeding results.     

A re-examination of curare action at the motor endplate.

Recent evidence indicates that curare, in addition to its competitive' interference with endplate receptors, can block open ionic channels by a 'non-competitive' action on the activated acetylcholine-receptor complex. These findings called for further study of the kinetic behaviour of endplate channels and their modification by curare. Examining impulse-evoked endplate currents and acetylcholine-induced current fluctuations, it is found that the lifetime of the open channel is shortened by relatively high concentrations of curare (greater than 5 micrometer), an effect which shows up most strikingly at hyperpolarized levels of membrane potential (-130 mV and above). No shortening of this kind is observed when a neuromuscular block of equal or greater intensity is produced by a dose of alpha-bungarotoxin. Two other neuromuscular blocking agents, gallamine and pancuronium are shown to have an action on channel kinetics which cannot be explained by competitive receptor binding, but conforms to the hypothesis of rapidly repeated blocking and unblocking of individual ion channels, which had been proposed originally to account for the endplate action of local anaesthetics.     

The in vitro effect of indomethacin on basal bone resorption, on prostaglandin production and on the response to added prostaglandins

Mouse calvaria were maintained in organ culture without serum additives. Basal active resorption, as measured by ⁴⁵Ca and hydroxyproline release, was significantly inhibited to 74% control levels by indomethacin (1.4 × 10⁻⁷ M). Prostaglandin F and prostaglandin E₂ production, determined by radioimmunoassay, were both significantly lowered by this concentration of indomethacin. DNA, protein and hydroxyproline synthesis, as indices of cell toxicity, were unaffected by low concentrations of indomethacin, while concentrations of 1.4 × 10⁻⁶M inhibited protein synthesis (p<0.005). In the presence of indomethacin (1.4 × 10⁻⁷M) both PGE₂ and PGF_2α stimulated resorption in a dose-dependent manner, with PGE₂ being the more potent. Neither prostaglandin affected hydroxyproline synthesis at low concentrations, but PGE₂ had a marked inhibitory action at a higher concentration (10⁻⁶M). In combination, the effects of PGE₂ and PGF_2α showed no evidence of synergism or any antagonistic action. The study shows that in vitro calcium and hydroxyproline resorption in the unstimulated mouse calvaria are inhibited by indomethacin at concentrations measured in serum during human therapy. The decreased PGF and PGE₂ production associated with this decreased bone resorption in the presence of non-toxic concentrations of indomethacin would suggest a role for these prostaglandins in maintaining the basal resorption of cultured bone.