Abstract. This study was performed on patients (n = 18) suffering from strictly defined hyperdynamic septic shock. Plasma faclors (C-reactive protein, acid al-glycoprotein, fibri nogen, fibrinopeptide A, fibrinogen-fibrin split products, factor XIII, antithrombin III, complement factors C3 and C4, interet-trypsin-inhibitor and CtrmacrogJobulin) measured during hyperdynamic septic shock were highly abnormal. The actjvation and consumption of dotting, fibrinolytic and complement factors due to systemspeeific proteinases (such as thrombokinase or plasminogen aetivators) seemed to be intensified by the nonspecific proteolytic activity of granuloeytic proteinases probably released by the action of endotoxins. Possible therapeutie measures {o maintain the endogeneous defenee meehanism against enhaneed proteolysis during septic shoek are diseussed.
In 4 cases of allergic vasculitis circulating immune complexes (IC) were demonstrated. Spontaneous and histamine induced vascular changes were studied by immunofluorescence microscopy. The early events in IC vasculitis were investigated at the ultrastructural level by immunoelectronmicroscopy using the peroxidase-antiperoxidase multistep technique. Our findings support the concept that human IC vasculitis is triggered by the deposition of circulating IC in the walls of postcapillary venules between endothelial cells, pericytes and the layers of the basal lamina. Tissue destruction is only secondary due to local complement activation and the release of lysosomal enzymes from chemotactically attracted leukocytes.
The effect of psoralen plus long wavelength ultraviolet light (UVA) on 3H-thymidine uptake of PHA stimulated human lymphocytes was investigated. PHA induced lymphocyte transformation was inhibited by the combined action of psoralen and UVA irradiation in a dose related manner. Inhibition of DNA-synthesis occurred at concentrations of psoralen that can be expected in the serum of patients treated by systemic photochemotherapy. No effect was noted at these psoralen concentrations in the absence of UVA irradiation. Also did UVA irradiation in the absence of psoralen not inhibit 3H-thymidine incorporation into PHA stimulated lymphocytes.
A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.
The effect of cortisol, dexamethasone, insulin and a liver cell growth promoting tripeptide on the secretion of plasma proteins into the medium of rat hepatocytes in monolayer cultures was studied. Cortisol and dexamethasone resulted in ~ 2.5-fold increase in the fibrinogen synthesis with general supression of album in and α-lipoprotein synthesis. On the other hand, insulin inhibited the biosynthesis of most plasma proteins except for the complement system and transferrin. Concentrations of α-lipoprotein, a-1-macroglobulin and haptoglobin were moderately elevated when the tripeptide Gly-His-Lys was applied in low concentration
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