Stephen M. Campbell

Lactoferrin binds to cell membrane DNA. Association of surface DNA with an enriched population of B cells and monocytes.

The binding of human 125I-labeled lactoferrin (LF) to a population of adherent mononuclear cells (ADMC) and nonrosetting lymphocytes (E-) was abolished by prior treatment of the cells with deoxyribonuclease (DNase), but not ribonuclease (RNase). When DNase-treated ADMC were incubated with exogenous DNA, the binding of 125I-LF was restored. Enzymatic digestion with other enzymes, trypsin, phospholipase D, and neuraminidase, did not significantly influence 125I-LF binding. Saturable binding of LF at 0 degrees C was demonstrated for both E- and ADMC, with equilibrium dissociated constants of 0.76 x 10(-6) M and 1.8 x 10(-6) M, respectively. E- cells bound 2.5 x 10(7) and ADMC bound 3.3 x 10(7) molecules of Lf at saturation. Cell membranes were isolated from ADMC, E- and E+ and reacted with 125I-labeled LF; significant binding was only seen with ADMC and E-. Prior treatment of the membranes with DNase abolished the binding. Immunofluorescence studies indicated that a population of ADMC and E-, but not E+, exhibited a peripheral staining pattern for LF. Prior treatment of ADMC and E- with DNase abolished the surface immunofluorescence. This study provides evidence that cell membrane DNA acts as a binding site for exogenous LF. This is a novel role for DNA that has not been previously reported. Furthermore, it points to a basic difference between E+ cells vs. ADMC and E- cells in respect to their possession of cell surface DNA.

Individual patient variations in the kinetics of intravenous immune globulin administration

Subjects with primary immunodeficiency received modified immune serum globulin (IGIV) intravenously at various dose levels in long-term therapeutic studies. Therapy was effective and essentially free from adverse reactions. Two pertinent observations were made relating to the attained levels of serum IgG. Over a dose range of 100-225 mg/kg, the serum IgG level directly reflects the dosage administered. Sequential analysis of serum levels of IgG demonstrated three patient populations in 14 subjects receiving 150 mg/kg. The largest group, nine patients, had progressive reduction of serum IgG values compatible with the half-life of the reagent, with a return to the original serum IgG level in four weeks. A second population of four patients had a slower reduction of serum IgG over the four-week period. IgG values were significantly elevated over baseline values at the time of the next due infusion. In one subject serum IgG values varied greatly with rapid drops and elevations unrelated to the infusion.

Is the tender point concept valid

The finding of multiple tender points is essential to the diagnosis of the fibrositis/fibromyalgia syndrome. Recent studies have shown that the tender point count seems to correlate with the presence of fibrositis symptoms, and can distinguish fibrositic from normal subjects. Although tender points are present in normal subjects, fibrositis patients have far more tender points that are much more tender. Further work is necessary to establish the reliability of tender point measurement, and to investigate and monitor changes in the tender point count with time or therapy.

A tutorial for students demonstrating adequate skills but inadequate knowledge after completing a medicine clerkship at the Oregon Health Sciences University.

Upon completing a clinical clerkship, some students demonstrate adequate clinical skills appropriate for that clerkship but do not demonstrate an adequate fund of knowledge or ability to apply their knowledge clinically. For such students, repeating all or a portion of the clerkship may not be appropriate. This study describes a tutorial provided such students after they had completed the medicine clerkship at the Oregon Health Sciences University. During a two-year period (academic years 1988–89 and 1989–90), six students were identified as needing remediation, and were enrolled in a tutorial coordinated by one faculty member with support from others. The experience was highly successful for all but one student, and the tutorial was uniformly viewed by the students who took it as one of their best experiences in medical school.

Indirect inhibition of myocyte RNA and protein synthesis by interleukin-1

Soluble mediators of the inflammatory response may directly influence myocardial function and metabolism in the absence of myocardial cell necrosis. Previous reported experimental data have demonstrated that the monokine interleukin-1 (IL-1) can produce myocardial depression and may influence muscle protein metabolism. To further investigate this hypothesis, IL-1 was added to neonatal rat cardiac muscle cell (MC) cultures with and without additional rat cardiac non-muscle cells (NMC). Incorporation of 3H-uridine or 14C-phenylalanine into acid-insoluble material was utilized as a measure of RNA or protein synthesis. IL-1 in concentrations of up to 500 units/ml had no effect on MC RNA or protein synthesis. When NMC were added to the MC culture, IL-1 exhibited a concentration-dependent inhibition of both RNA and protein synthesis, with effects apparent at concentrations as low as 5 units/ml. Supernatants from IL-1-treated NMC cultures exerted a dose dependent reduction on the incorporation of radiolabeled precursor into MC cultures, suggesting production of a soluble substance mediating the IL-1 effect. Supernatants from IL-1 treated rat skin fibroblasts or rat skeletal muscle myoblasts increased MC radiolabeled precursor incorporation slightly, in contrast to the decrease seen with NMC supernatant. Furthermore, IL-1 treated NMC supernatant had no inhibitory effect on skeletal myoblasts. We conclude that IL-1 decreases protein and RNA synthesis in MC cultures through a second mediator elaborated from the NMC population.