Modulation of the expression of interleukin 2 receptors of human thymocytes by recombinant interleukin 2

The effect of purified recombinant interleukin 2 on the expression of the receptors for interleukin 2 by human thymocytes was examined. Interleukin 2 augmented the expression of interleukin 2 receptors and interferon-gamma synthesis by thymocytes activated with concanavalin A, and it was required to maintain the growth of thymocytes in vitro and the expression of interleukin 2 receptors. The increase observed in the number of receptor bearing thymocytes and in the density of receptors due to interleukin 2 occurred within the first 2 days of culture. Dexamethasone inhibited the expression of interleukin 2 receptors, the synthesis of interferon-gamma, and the early proliferation and protein synthesis of lectin-activated thymocytes during the first 2 days of culture. The inhibitory effect of dexamethasone on the expression of interleukin 2 receptors and on the synthesis of interferon-gamma was reversed by interleukin 2, whereas its effect on proliferation and on protein synthesis during the first two days of culture was not reversed by interleukin 2. Interleukin 2 induced the proliferation of thymocytes in vitro, even in the absence of activation by lectin; however, the number of cells displaying receptors which could be detected with anti-Tac remained low throughout the first week of culture and interferon-gamma synthesis was not observed. Nonetheless, interleukin 2-induced proliferation was inhibited by anti-Tac on a dose dependent manner. The results of the study document that recombinant interleukin 2, like purified natural interleukin 2, is required for the expression of interleukin 2 receptors, for interferon-gamma synthesis, and for the growth of thymocytes in vitro.     

D-2 dopamine receptors in the frontal cortex of rat and human

D-2 dopamine receptors and serotonin receptors in the frontal cortex of rat and human were labelled with 3H-spiroperidol. The D-2 receptors were then distinguished in 4 ways. Dissociation of spiroperidol was biphasic, indicating two populations of sites. Cinanserin in competition with 3H-spiroperidol exhibited high (75%) and low (25%) affinity sites. Dopamine and LY 141865 in competition with 1.25 nM 3H-spiroperidol exhibited high (20-25%) and low (80-75%) affinity sites in the absence of cinanserin, while in the presence of 300 nM cinanserin only the high affinity sites remained. Lesioning of the dopaminergic meso-cortical pathway increased the number of cinanserin-resistant sites by 26%. Thus 3H-spiroperidol binding in the presence of cinanserin can be used to selectively label D-2 receptors in the frontal cortex.     

Addison,pernicious anemia and adrenal insufficiency

In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison''s disease. Considering the importance of these works, there remains a great deal of confusion about them. Contrary to what many historians have written, a review of Addison''s original publications demonstrates a firm appreciation of the distinction between pernicious anemia and adrenal insufficiency, based particularly on the discoloration of the skin in these conditions. Three major sources of possible confusion for historians who are attempting to understand Addison''s views include Addison''s early attempts to link pernicious anemia with disease of the supra-renal capsules, Addison''s redefinition of pernicious anemia in his monograph on adrenal disease, and several confusing statements made by Wilks and Daldy in the first reprint of Addison''s monograph.     

Analysis of factors restricting the use of binomial statistics for studying transmitter release in neuromuscular junctions

Binomial parameters of transmitter secretion were calculated on the basis of analysis of synaptic potentials in the frog sartorius muscle. Negative values of the parameter p were found in some synapses. This happened most often in low Ca²⁺ concentrations and with low amplitude of miniature end-plate potentials. The results were interpreted in terms of a model assuming spatial heterogeneity of probability of transmitter quantum release at different release points. Simulation of transmitter secretion by computer showed that the appearance of negative values of the parameter p and incorrect estimates of n experimentally are connected with the form of distribution of probability of transmitter quantum release in the synapse and with the amplitude of miniature potentials.S. V. Kurashov Kazan' Medical Institute, Ministry of Health of the RSFSR. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 182–189, March–April, 1984.     

Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli

Auranofin, a new oral antirheumatic gold compound, in concentrations achieved therapeutically, inhibits neutrophil phagocytosis, chemotaxis, chemiluminescence, reduction of cytochrome c, and release of lysosomal enzymes. To further characterize the mechanism by which auranofin affects neutrophils, we studied the effects of auranofin on unstimulated properties and functions of neutrophils as well as on rapidly stimulated functions. When examined by electron microscopy, 4 micrograms/ml of auranofin significantly decreased the number of visualized centriole-associated microtubules in resting cells. Furthermore, auranofin inhibited neutrophil spreading on glass and caused a decrease in negative surface charge (electrophoretic mobility). In addition, auranofin inhibited several fmet-leu-phe-stimulated responses such as shape change, increases in centriole-associated microtubules, decreases in surface charge, and elicited membrane potential changes (di-O-C5(3) dye response). Auranofin (1 micrograms/ml) inhibited fmet-leu-phe-stimulated superoxide and hydrogen peroxide production by 80% (p less than 0.05), and also increased the affinity of receptors for fmet-leu-phe (from Ka 0.035 to Ka 0.48, p less than 0.001). Auranofin also affected neutrophil responses to phorbol myristic acetate (PMA). The total amount of PMA-stimulated superoxide production was suppressed by as little as 0.4 micrograms/ml of auranofin, but the lag time for activation was shortened by low concentrations of auranofin (0.5 to 1 microgram/ml). Four micrograms per milliliter of auranofin suppressed the decrease in surface charge induced by PMA. However, auranofin did not influence superoxide production elicited by the ionophore A23187. The results indicate that auranofin affects the earliest detected responses in neutrophil activation by certain receptor-mediated stimuli.     

Degradation of sugar cane bagasse by several white-rot fungi

Forty-two white-rot fungi isolated in South America were incubated with long fibre sugar cane bagasse (LFB). The residual composition of LFB was determined after white-rot decay at 30 and 60 days. The ratio of residual lignin to residual lignin to residual cellulose (RL/RC) of untreated material (LFB) was 0.48. After white-rot-decay, the residual material with lower RL/RC ratios indicated that mainly lignin was degraded. In only 30 days, Phlebia sp. MVHC 5535, Athelia sp. MVHC 5509 and Spongipellis pachyodon MVHC 5019 caused a decrease in the RL/RC ratio to 0.36, 0.37 and 0.38, respectively, while it took 60 days for Ganoderma applanatum MVHC 5347, Hyphodontia sp. MVHC 5544, Panus tigrinus MVHC 5400, Stereum sp. MVHC 5113, Phellinus punctatus MVHC 5346 and MVHC 6388 to reach a ratio lower than 0.40. No correlation was found between the amount of some ligninolytic enzymes secreted and the residual composition of bagasse after white-rot fungi fermentation. Most of the fungal strains caused an increase in the relative amount of residual cellulose, indicating that hemicellulose was the preferred energy source.     

Enhanced resistance of the myocardium to stress injury and excess calcium in spontaneously hypertensive rats

Extensibility, contractile function and resistance to excess calcium of the right atrium myocardium were studied in normotensive Wistar-Kyoto and August rats and in spontaneously hypertensive rats (SHR). It was shown that long-term stress results in a decrease in the measured parameters in normotensive animals. SHR do not show any stress-induced disturbances. It was discovered that in intact SHR rats, the myocardium has a greater resistance to excess calcium, indirect evidence for higher efficiency of the Ca-pump of the sarcoplasmic reticulum in cardiomyocytes of SHR animals, which is apparently a constituent part of the mechanism of such animals' heart increased resistance to stress-induced damage.