1Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the endogenous nitric oxide synthase inhibitors N0-monomethyl-L-arginine and NG,NG-dimethy-L-arginine to citrulline, was identified by Western blotting in rat and human tissue homogenates.2 S-2-amino-4(3-methylguanidino)butanoic acid (4124W) inhibited the metabolism of ["4C]-N0-monomethyl-L-arginine to ["4C]-citrulline by rat liver homogenates (IC50 416 + 66 giM; n = 9), human cultured endothelial cells (IC50 250 + 34 gLM; n = 9) and isolated purified dimethylarginine dimethylaminohydrolase. 3 Addition of 4124W to culture medium increased the accumulation of endogenously-generated N',N0-dimethy-L-arginine in the supernatant of human cultured endothelial cells from 3.1 + 0.3 to 5+0.7 ,M (n= 15; P<0.005). 4 4124W (1 uM-1 mM) had no direct effect on endothelial nitric oxide synthase activity but caused endothelium-dependent contraction of rat aortic rings (1 mM 4124W increased tone by 81.5 + 9.6% of that caused by phenylephrine 100 nM). This effect was reversed by L-arginine (100 giM). 4124W reversed endothelium-dependent relaxation of human saphenous vein (19.2 + 6.7% reversal of bradykinin-induced relaxation at 1 mM 4124W). 5 These data suggest that inhibition of dimethylarginine dimethylaminohydrolase increases the intracellular concentration of N',N0-dimethyl-L-arginine sufficiently to inhibit nitric oxide synthesis.Inhibiting the activity of DDAH may provide an alternative mechanism for inhibition of nitric oxide synthases and changes in the activity of DDAH could contribute to pathophysiological alterations in NO generation.

It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

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SummaryThe IgE-binding proteins in soybeans were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the frac tionated soybean proteins probed with the sera of the patients with atopic dermatitis. About 20% of the patients examined were shown to have specific IgE antibodies to soybean proteins. At least 16 soybean proteins with molecular weights ranging from about 70,000 to 14,000 were rec ognized by the sera of the patients: 10 major IgE-binding components were found in the 7S-globulin fraction, and the others mainly in the 2S-globulin and whey fractions. The IgE antibodies of the patients bound most strongly and frequently to a unique protein with molecular weight of about 30,000 in the 7S-globulin fraction, which appeared to be the major allergen in soybeans and was named as Gly m Bd 30K. The proteins in the 11 1S-globulin fraction were scarcely recognized by the patients' sera and assumed to be less allergenic for the patients with atopic dermatitis.