SUMMARY Sera from 41 patients with systemic lupus erythematosus (SLE), 87 controls with various diseases, and 30 normal subjects were examined for poly (adenosine diphosphate-ribose) and ds DNA binding. Elevated levels of poly (ADP-ribose) binding were found in 73 % of the SLE patients compared with 58 % who had raised ds DNA binding. In a further study of 160 sera from 27 patients with SLE, levels of antipoly (ADP-ribose) antibodies were shown to correlate with clinical activity better than either anti-ds DNA or ss DNA antibodies.Poly (ADP-ribose) is a nuclear polymer formed from nicotinamide adenine dinucleotide (NAD) by action of the chromatin bound enzyme, poly (ADP-ribose) polymerase, with the loss of the nicotinamide moiety. Its structure and physiochemical characteristics have been reviewed,1 2 though its precise function within the nucleus remains unknown.Antibodies to a variety of nuclear antigens including double-stranded (ds) DNA, single-stranded (ss) DNA, polyribonucleotides, ribosomes, ds and ss RNA, both synthetic and naturally occurring, have been reported in systemic lupus erythematosus (SLE).3-8 In particular, ds DNA antibodies are important in the diagnosis of the disease.9Recently the occurrence of antibodies to poly (ADP-ribose) has been reported."0 Okolie and Shall'1 have demonstrated in a preliminary study that these antibodies show specificity for SLE. However, the number of patients with other diseases examined by them was comparatively small. Therefore one of the aims of this investigation was to examine a larger group of patients with SLE and related diseases in order to compare the specificity of autoantibodies to poly (ADP-ribose) with ds DNA. The latter were tested with a widely used, commercially available kit.It has also been reported that antibodies to nuclear

The nuclei of Plasmodium yoelii nigeriensis contain an enzyme, ADP-ribosyltransferase, that will incorporate the ADP-ribose moiety of NAD+ into acid-insoluble product. The time, pH and temperature optima of this incorporation are 30 min, 8.5 and 25 degrees C respectively. Maximum stimulation of the enzyme activity is obtained with 1.0 mM-dithiothreitol or 2.0 mM-2-mercaptoethanol. Ca2+ and Mg2+ ions at optimum concentrations of 5 mM and 10 mM respectively stimulated the activity of the enzyme by 21% and 91%. The enzyme activity is, however, inhibited by 24% in the presence of 10 mM-MnSO4. The substrate, NAD+, exhibits an apparent Km of 500 microM, and the activity of the enzyme is inhibited by four chemical classes of inhibitors: nicotinamides, methylxanthines, thymidine and aromatic amides. The inhibitors are effective in the following increasing order: nicotinamide less than 3-aminobenzamide less than thymidine less than 5-methylnicotinamide less than theophylline less than m-methoxybenzamide less than theobromine. The enzyme activity is also inhibited by some DNA-binding anti-malarial drugs.

Male infant nonhuman primates ( M . nemestrina) born in captivity were used in the study. They were divided into three groups. The first group of three animals was fed a 20% casein diet and the second group of six monkeys received a 2.0% casein diet. The third group of four monkeys received a 20% casein diet totally devoid of ascorbic acid for 3.5 weeks before the diet was supplemented with ascorbic acid (20 mg/kg diet). All the diets were given to the animals in two daily rations of 100 glanimal. The monkeys fed a 2% casein diet failed to grow, and after about 3.5 months showed variable degrees of edema, hypoalbuminemia, evidence of psychomotor disturbance, depressed plasma levels of many essential amino acids, and other features consistent with the diagnosis of protein-energy malnutrition. Examination of the brains revealed significant alterations in the levels of histidine (+ 172%) and homocarnosine (+ 146%) in comparison with the control well-fed monkeys. Associated with the increase in brain histidine was a marked elevation of brain histamine level. Protein deficiency also led to poor brain retention of ascorbic acid but not to the same degree observed in the ascorbic acid-deficient animals. The latter group of animals, after receiving their diet for about 8 months, demonstrated a modest elevation in the plasma levels of most amino acids in comparison with controls. Ascorbic acid deficiency elicited a signifi-cant reduction (p < 0.01) in brain level of histidine, with

Electron microscopy of hepatic cells from protein-deficient young rats revealed extensive breakdown of the rough endoplasmic reticulum into fragments and vesicles whose membranes appeared fully studded with ribosomes. Additionally, there was biochemical evidence of marked disaggregation of polysomes (n > 2), and this was more prominent in the membrane-bound than in free polysomes. Protein malnutrition increased the proportion of membrane-bound ribosomes which were salt-releasable and therefore temporarily non-functional. It has been concluded that disaggregation of membrane-bound polysomes induced by malnutrition does not necessarily imply detachment of the monomeric ribosomes from the endoplasmic membrane into the pool of free ribosomes, which probably has a separate polyribosomal cycle.

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