Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency > 2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45-53 degrees C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of > or = 0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies < 0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-D-aspartate receptor antagonist.

Lythgoe and Tansley 1 investigated the effect of varying the brightness of field surrounding a patch used for testing critical flicker frequency (hereafter c.f.f.), and found in general that the c.f.f. increased as the brightness of the surrounding field increased, but they carried the brightness of the surrounding field only up to the level of the Talbot brightness of the test spot.Graham and Granit 2 found, as Lythgoe and Tansley had found, that a steady stimulus equal to the Talbot brightness of the intermittent stimulus gives a higher c.f.f. than the intermittent stimulus alone. They alleged that this is evidence of a "true spatial summation which implies that a higher state of excitation may be produced in a given area through the agency of impulses from any area reasonably near to it." Now flicker so far as the retina is concerned involves an alternation of strong and weak phases of activity, and it is the difference between the phases and not their absolute strength that counts. Even though summation might make the strong phases stronger, as Graham and Granit suppose, it ought to make the weak phases stronger also, so that it is difficult to see how summation could raise the c.f.f.When the brightness of the steady stimulus was made brighter than the Talbot brightness of the intermittent * Beneficiary of a Grant-in-aid for Research in Neurophysiology from the Rockefeller Foundation.1 Lythgoe, R. J. and Tansley, K., The adaptation of the eye: its relation to the critical frequency of flicker, lied.

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Objective. To study eluates of intravenous gamma globulin (IVGG) prepared from affinity columns of human cationic IgG myeloma proteins bearing anti-DNA idiotype (Id) markers 1616, F4, 31, and 8.12 for possible anti-Id (combining site) blocking activity.Methods. Anti-DNA idiotypic antibody activity was studied in 3 preparations of IVGG containing high, medium, and low levels of IgG anti-F(ab'),, and in 4 other commercial IVGG preparations. Affinity-purified IgG anti-DNA (APAD) from systemic lupus erythematosus (SLE) patients was biotinylated, and binding to DNA coated on enzyme-linked immunosorbent assay plates was used to measure anti-DNA antibody activity. IVGG was adsorbed to Sepharose 4B affinity columns linked to a panel of cationic human IgG myeloma proteins positive for anti-DNA Id markers 1616, F4, 31, and 8.12. Material adsorbing to such columns was eluted at low pH (2.5) and after neutralization, tested for its ability to inhibit biotinylated APAD reacting with DNA.Results. Only 0.05-0.9% of IVGGs bound firmly to Id affinity columns. These IVGGs were then eluted, using pH 2.5 glycine-saline and eluates neutralized to pH 7.4. Column flowthrough and eluate fractions were compared for their ability to block SLE APAD reacting with DNA. Significant inhibition of SLE APAD combining sites was observed with eluates from anti-DNA Id aftinity columns; however, no correlation between IVGG anti-F(ab'), activity and true anti-Id blocking of APAD was apparent. Submitted for publication June 13, 1996; accepted in revised form October 14, 1996. tivity was recorded for IVGG eluates from human cationic myeloma columns devoid of the 4 anti-DNA Id markers. DNase treatment of IVGG or Id column eluates did not affect anti-Id blocking activity. Thus, all detectable anti-DNA idiotypic antibody capable of blocking SLE anti-DNA combining sites bound to Id+ affinity columns. Column eluates also showed some relative concentration of IgG anti-DNA activity, which was of lower affinity for DNA than antibodies also present in eluates which blocked anti-DNA combining sites.Conclusion. The presence of both anti-DNA and antiidiotypic (anti-combining site) activity in human anti-DNA Id column eluates indicates that epibodies from IVGG are relatively concentrated when this strategy is used. This approach may lead to a new strategy for treatment of SLE nephritis.Systemic lupus erythematosus (SLE) seems to represent a human disorder in which the immune system runs amok-often producing autoantibodies with anti-DNA, anti-Ro, or antiplatelet specificity which are capable of initiating various salient clinical features of the disease itself. When Jerne originally proposed his network theory (1,2), it was actually based on earlier primary observations that each antibody had its own unique specificity and, moreover, that certain groups of autoantibodies sometimes shared cross-reactive idiotypes which were related to shared similar specificities within their respective V regions (3-5). The concept of an idiotype-antiidiotype (Id-anti-Id) network...