Planning science (a generation after Lewis Thomas)

Andrew Marks’ recent editorial eloquently reiterated a concern that many of us have voiced before, that the current policies and practices of the NIH are not serving the public well.     

C-Reactive Protein in Systemic Lupus Erythematosus

The presence of C-reactive protein (CRP) was determined in the sera of 70 patients with systemic lupus erythematosus (SLE), 24 patients with rheumatoid arthritis (RA), and 17 patients hospitalized with acute infections. CRP (precipitin reaction > 3 mm) was present in only 2 of 50 patients with active, uncomplicated SLE (4%). However CRP was found in the sera of 11 patients with active SLE in the presence of superimposed infection. Treatment of the intercurrent infection resulted in the loss of CRP from the sera of these SLE patients. CRP was found in 85% of patients with active RA and in 100% of non-SLE infected patients. Appropriate treatment of the latter group resulted in loss of CRP from the convalescent sera. Corticosteroid therapy did not appear to influence the presence of CRP in the RA or SLE groups. Fourteen of 50 noninfected patients (28%) with active SLE were not receiving steroids at the time of CRP negativity. Appropriate experiments with mixed sera failed to demonstrate serum factors that could influence CRP precipitation in the CRP-negative SLE group. These studies suggest that patients with active SLE usually do not have CRP in their sera, and the results distinguish this group of patients from those with active RA, a disease generally marked by CRP positivity. Moreover, the finding of significant CRP precipitin in the sera of SLE patients may suggest the presence of superimposed infection.     

Superoxide anion generation by human neutrophils exposed to monosodium urate. effect of protein adsorption and complement activation

We studied the capacities of naked and proteincoated monosodium urate (MSU) crystals to stimulate superoxide anion (O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document}) release by human polymorphonuclear leukocytes (PMN). Uncoated MSU stimulated significant O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} production by cytochalasin B-treated PMN. Precoating MSU with IgG caused an increase in mean O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} production, whereas precoating heated MSU with serum or plasma inhibited O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} release. Unheated MSU crystals, which activate complement to a greater extent than heated crystals, also provoked O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} generation, an effect again abrogated by precoating with serum but not with plasma. Coincubation of unheated MSU and plasma resulted in an enhancement of O₂\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} generation. The results of these experiments support the hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response.     

Bertram M. Gesner, 1931–1968

‘Medicine does not end in hospitals, as is often believed, but merely begins there. In leaving the hospital, a physician, jealous of his title in its scientific sense, must go into the laboratory; and there by experiments on animals he will seek to account for what he has observed in his patient. There, in a word, he will achieve true medical science.”—Claude Bernard, 1865     

Generation of C5-derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus

Activated complement components and immune complexes cause neutrophil aggregation in vitro and in vivo. We have previously demonstrated that sera of patients with active systemic lupus erythematosus (SLE) provoke the aggregation of normal neutrophils in vitro. In this study the serum or plasma of 4 such patients was fractionated on Sephadex G-75. In 3 patients neutrophil aggregating activity (NAA) was detectable in fractions which coeluted with reference C5-derived peptides (estimated molecular radius of 17,000). The activity of these fractions was inhibitable by antibodies to human C5. All patients also had activity that coeluted with reference immune complexes. In addition, material of apparent molecular radius under 12,000 that contributed to the neutrophil aggregating activity of SLE sera was detected. In separate experiments increased levels of C5a desarg were demonstrated during active disease by means of radioimmunoassay. These findings suggest that multiple neutrophil aggregants circulate during the course of active SLE. The formation of intravascular leukoaggregates may contribute to endothelial injury in this disease.