The conformations of Glu-plasminogen and defined proteolytic fragments, in the presence and absence of 6-aminohexanoic acid (6-AHA), trans-4-(aminomethyl)cyclohexanecarboxylic acid (t-AMCHA), and benzamidine, were studied using three methods: size-exclusion high-performance liquid chromatography (SE-HPLC), small-angle X-ray scattering (SAXS), and dynamic laser light scattering (DLLS). The well-documented conformational change of Glu-plasminogen with 6-AHA or t-AMCHA was measured as a decrease in molecular elution time by SE-HPLC (8.93 +/- 0.01 to 8.32 +/- 0.01 min) and increases in radius of gyration (30.7 +/- 0.1 to 49.8 +/- 0.3 A) and Stokes radius (40.6 +/- 0.3 to 48.5 +/- 0.3 A) by SAXS and DLLS, respectively. The addition of benzamidine to Glu-plasminogen resulted in a conformation (radius of gyration 41.0 +/- 0.4 A and Stokes radius 46.6 +/- 0.3 A) distinct from that in the presence of 6-AHA. 6-AHA, but not benzamidine, induced significant conformational changes in Lys-plasminogen and kringles 1 + 2 + 3 + 4 + 5. We conclude that Glu-plasminogen adopts three distinct conformations involving two intramolecular interactions: one mediated by regions of the NH2-terminal peptide and kringle 5, competed for by 6-AHA or benzamidine, and the other possibly between kringles 3 and 4, competed for by 6-AHA but not benzamidine.

This review describes the ways in which the primary bradycardia and peripheral vasoconstriction evoked by selective stimulation of peripheral chemoreceptors can be modified by the secondary effects of a chemoreceptor-induced increase in ventilation. The evidence that strong stimulation of peripheral chemoreceptors can evoke the behavioural and cardiovascular components of the alerting or defence response which is characteristically evoked by novel or noxious stimuli is considered. The functional significance of all these influences in systemic hypoxia is then discussed with emphasis on the fact that these reflex changes can be overcome by the local effects of hypoxia: central neural hypoxia depresses ventilation, hypoxia acting on the heart causes bradycardia and local hypoxia of skeletal muscle and brain induces vasodilatation. Further, it is proposed that these local influences can become interdependent, so generating a positive feedback loop that may explain sudden infant death syndrome (SIDS). It is also argued that a major contributor to these local influences is adenosine. The role of adenosine in determining the distribution of O 2 in skeletal muscle microcirculation in hypoxia is discussed, together with its possible cellular mechanisms of action. Finally, evidence is presented that in chronic systemic hypoxia, the reflex vasoconstrictor influences of the sympathetic nervous system are reduced and/or the local dilator influences of hypoxia are enhanced. In vitro and in vivo findings suggest this is partly explained by upregulation of nitric oxide (NO) synthesis by the vascular endothelium which facilitates vasodilatation induced by adenosine and other NO-dependent dilators and attenuates noradrenaline-evoked vasoconstriction. Correspondence

The carotid bodies of rats made chronically hypoxic by breathing 12% O 2 in a normobaric chamber (inspired PO 2 91 mmHg) were compared with those of controls. Serial 5-µm sections of the organs were examined using an interactive image analysis system. The total volume of the carotid bodies was increased by 64%. The total vascular volume rose by 103% and was likely due to an increase in size of the large vessels (>12 µm lumen diameter) because the small vessel (5-12 µm lumen diameter) volume did not increase significantly while the small vessel density tended to decrease. The extravascular volume was increased by 57%. Expressed as a percentage of the total volume of the organ, the total vascular volume did not change, but the small vessel volume was significantly decreased from 7.83 to 6.06%. The large vessel volume must therefore have been increased. The proportion occupied by the extravascular volume was virtually unchanged (84 vs 82%). In accordance with these findings, the small vessel endothelial surface area per unit carotid body volume was diminished from 95.2 to 76.5 mm -1 , while the extravascular area per small vessel was increased from 493 to 641 µm 2 or by 30%. In conclusion, the enlargement of the carotid body in chronic hypoxia is most likely due to an increase in total vascular volume, mainly involving the large vessels, and to an increase in extravascular volume. This is in contrast to our previously published findings indicating that in the spontaneous insulin-dependent diabetic rat the enlargement of the carotid body is due solely to an increase in extravascular volume. Some of these data were previously reported in abstract form

No abstract

The present study examined secretion of urokinase and tissue-plasminogen activator by epidermal cells in the presence of psoriatic or uninvolved skin fibroblast-conditioned medium. Using zymographic analyses, a 54kD lysis band and a small 110kD band derived from urokinase could be detected in the harvest fluid from keratinocytes treated with both psoriatic and uninvolved fibroblast-conditioned medium, as well as very weak lysis bands of 63kD and 120kD derived from tissue-plasminogen activator in the harvest fluid treated with psoriatic fibroblast-conditioned medium, but not with uninvolved fibroblast-conditioned medium.