A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus.

In systemic lupus erythematosus, antibodies against double-stranded DNA are a major contributor to renal disease. We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA. This sequence is also present in the extracellular domain of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a and NR2b. Here we show that the NR2 receptor is recognized by both murine and human anti-DNA antibodies. Moreover, anti-DNA antibodies with this cross-reactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus erythematosus contains these antibodies and also mediates neuronal death via an apoptotic pathway. These observations indicate that lupus antibodies cross-react with DNA and NMDA receptors, gain access to cerebrospinal fluid and may mediate non-thrombotic and non-vasculitic abnormalities of the central nervous system.     

Study of permeation and blocker binding in TMEM16A calcium-activated chloride channels

We studied the effects of mutations of positively charged amino acid residues in the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E, K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not affected, and only K613E showed a lower current density. K628E and R761E affect anion selectivity without affecting Na⁺ permeation, whereas K613E, R646E and the double mutant K613E + R646E affect anion selectivity and permeability to Na⁺. Furthermore, altered blockade by the chloride channel blockers anthracene-9-carboxylic acid (A-9-C), 4, 4''-Diisothiocyano-2,2''-stilbenedisulfonic acid (DIDS) and T16inh-A01 was observed. These results suggest the existence of 2 binding sites for anions within the pore at electrical distances of 0.3 and 0.5. These sites are also relevant for anion permeation and blockade.     

An electron paramagnetic resonance study of free radicals in cells.

An electron paramagnetic resonance study was performed on cell lines of the following strains: HeLa, 37RC, L, FLC, NRK/RSV, 3T3/SV40. Unsynchronized and synchronized HeLa cells were studied with particular attention paid to the relation between growth and free radical concentration. Free radical levels were shown to be a function of the growth stage and different phases of the cell cycle.     

Is there energy conservation in amenorrheic compared with eumenorrheic distance runners?

The female distance runner is considered at high risk for secondary amenorrhea and reduced spinal bone mineral, and recent studies have suggested that these disturbances might be nutritionally or metabolically linked. The present study investigated 1) whether there is a physiological basis by which the amenorrheic runner might maintain weight at a lower than expected caloric intake, i.e., conservation of energy, and 2) the potential interactions of reduced energy intake, secondary amenorrhea, and reductions in bone density. Subjects included 13 elite female distance runners, 8 amenorrheic and 5 eumenorrheic, and 5 untrained female controls. Body composition by hydrostatic weighing, bone density and mineral content by dual-photon absorptiometry, and blood samples for hormonal analyses (once per week for 4 wk) were obtained, as were duplicate measures for resting metabolic rate, thermic effect of a meal, and the energy cost of specific (treadmill) and nonspecific (cycle ergometer) physical activity. Energy intake and energy expenditure were estimated by 3-day logs. Energy intakes did not differ (1,781, 1,690, and 1,763 kcal), nor did energy expenditures (2,480, 2,314, and 2,268 kcal), for the amenorrheic and eumenorrheic runner and control groups, respectively. The difference between reported energy intake and estimated energy expenditure of 500-700 kcal was likely due to underreporting or restricting intake, inasmuch as there was no evidence of energy conservation. A possible link was suggested between disordered eating, secondary amenorrhea, and bone mineral loss.