Key role of integrin αIIbβ3 signaling to Syk kinase in tissue factor-induced thrombin generation

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.     

Diurnal rhythm of ethanol metabolism in the rat

Summary Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.Supported by a grant from the US National Aeronautics and Space Administration.     

Immunochemical identification of vitellogenin in the serum of the newtTriturus cristatus

Summary The hematic yolk precursor — vitellogenin — has been identified immunochemically in the serum of estrogenized females of the newtTriturus cristatus by employing an antiserum prepared against yolk proteins.     

Effect of adapting target size on the gain of the surround response mechanism in X- and Y-cells in cat retina

Summary The adaptation field of the surround mechanism of X and Y retinal ganglion cells in the cat was assessed with variable size, unmodulated adapting spots. Both an on-inhibition measure and an off-discharge measure of surround gain was used. Results suggest that the surround mechanism in Y-cells is strongest in the receptive field middle but weak or nonexistent in the middle of X-cell receptive fields.Acknowledgment. This research was supported by Public Health Service grant No. EY 00701.     

Recurrent inhibition of the monosynaptic reflex in the upper caudal cord of the cat

Summary In spinal cats both ipsi- and contralateral antidromic volleys in the 3rd sacral ventral roots produce recurrent inhibition of the monosynaptic reflex evoked by stimulation of the 1st caudal dorsal root and recorded from the corresponding ventral root.     

Functional consequences of treating turkey liver fructose-1,6-bisphosphatase with penicillin G

Summary Treatment of turkey liver fructose-1,6-bisphosphatase with penicillin G progressively inactivated the enzyme and desensitized the enzyme toward high substrate inhibition. The treatment also led to reduced sensitivity to AMP inhibition and the loss of cooperative interaction among AMP-binding sites. These altered properties were not reversed by dialysis, but were prevented when treatment with penicillin G was performed in the presence of substrate.This work was in part supported by grant RR-8006 from the General Research Branch, Division of Research Resources, NIH (USA) and in part by Faculty Research Grant from Southern School of Pharmacy, Mercer University, Atlanta (Georgia, USA).     

λ-Prophage induction by furocoumarin photosensitization

Summary Furocoumarin photosensitization induces -prophage from lysogenicEscherichia coli cells; this effect is clearly due to the photoreaction that furocoumarins give with DNA, and it appears connected with the formation of monoadducts rather than of diadducts (cross-links).Acknowledgments. The authors wish to express their thanks to Dr L. Conventi, Microbiology Institute of Padua University, for generously donating theE. coli strains used in this work.