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Biomedical subjects

H Gewurz

Publications and source records attributed to H Gewurz.

At least 145 records · Page 8Linked to original sources
PubMed1976

Purification of cobra venom factor from phospholipase A contaminant.

It has been demonstrated that cobra venom factor prepared by the usual combination of ion exchange chromatography and sephadex gel filtration is contaminated by substantial amounts of a 'heavy' phospholipase A. The two activities may be separated by isoelectric focusing. Cobra venom factor focuses at pH between 5-75 and 6-75 whereas the phospholipase is all found at pH below 7-75. In certain test systems, particularly in vitro, and particularly where albumin concentrations are low, the contaminating phospholipase may produce effects that have been attributed to complement activation.

Chromatography, Gel↗
PubMed1975

Interactions of C-reactive protein with the complement system. II. C-reactive protein-mediated consumption of complement by poly-L-lysine polymers and other polycations.

Cationic homopolymers of poly-L-lysine were found to activate complement (C) via C-reactive protein (CRP) and deplete C3 and C5 as well as early-acting C components. Maximum C consumption was obtained with polymers of 2,000-8,000 daltons; polymers of 1,700, 11,000, and 23,000 daltons were intermediate in reactivity, while L-lysine, lysyl-L-lysine, tetra-L-lysine, and polymers of 70,000-400,000 daltons lacked significant C-consuming activity. Naturally occurring polycations which consumed C in the presence of CRP included myelin basic proteins, cationic proteins of rabbit leukocytes, and both lysine- and arginine-rich histones; poly-L-arginine polymers of 17,000 but not 65,000 daltons also were C-consuming. Polycations without such reactivity included poly-L-orithine (5,000 and 165,000 daltons), egg white and human lysozymes, and Polybrene. The polycations which failed to induce C consumption via CRP, inhibited its consumption by both active polycations and by C-polysaccharide (CPS). The relative inhibitory capacity of phosphorylcholine and polycations in CPS- and polycations-CRP systems was consistent with the concept that phosphate esters and polycations react at the same or an overlapping combining site. The ability of certain polycations to activate C via CRP increases the potential for initiation of host reactions via C. The capacity of other polycations to inhibit C activation via CRP introduces a potential for physiologic or pharmacologic manipulation. These considerations would seem to expand the potential role of CRP in the initiation and modulation of the inflammatory response.

Animals↗
PubMed1975

Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions.

C-reactive protein (CRP) is an acute phase protein which shares with the immunoglobulins the ability to induce precipitation and agglutination reactions and activate the complement system. We report here that purified human CRP binds selectively to human T lymphocytes, inhibits their ability to form spontaneous rosettes with sheep erythrocytes and inhibits their response to allogeneic cells in mixed lymphocyte culture reactions; it fails to inhibit phytohemagglutinin- or concanavalin-A-induced mitogenesis. CRP does not bind to human B lymphocytes, nor does it alter the following B-cell functions: binding to activated complement components or the Fc portion of immunoglobulins, mediation of antibody-dependent cytotoxicity reactions or the ability of allogeneic cells to stimulate a mixed lymphocyte culture reaction. Human CRP shows similar selective binding with murine T lymphocytes. It therefore seems that binding of CRP is a property of T lymphocytes or a subpopulation thereof, and can result in modulation of certain of the T-cell functional characteristics in vitro. We suggest that CRP may play a role in modulating T-cell functions during the inflammatory state.

Animals↗
PubMed1975

Significane of intravascular coagulation in canine endotoxin shock.

The contribution of disseminated fibrin clot formation to the pathogenesis of canine endotoxin shock was explored in control dogs and in those defibrinated with a purified fraction of Malayan pit viper venom. The hemodynamic and humoral responses after the administration of an intravenous challenge dose of Escherichia coli endotoxin were comparable as was mortality. It is concluded that, although the role of the coagulation sequence in canine endotoxin shock is unclear, it does not appear to be determinative.

Animals↗
PubMed1975

Effects of anesthesia, surgery and inflammation upon host defense mechanisms. I. Effects upon the complement system.

Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groupds. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the 'reactor state', a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

Anesthesia, General↗
PubMed1975

Binding of the complement intermediate C56 to zymosan in acute phase human sera.

C56 is known to appear in the fluid phase when zymosan is incubated at 37 degrees C with certain acute phase 'reactor' sera. In the present study, C56 was detected bound to the zymosan particle prior to its appearance free in solution. In reactor sera C56 was formed and released with kinetics similar to that of the generation and decay of a C56-binding site formed when zymosan was incubated with normal serum. Bound and fluid phase C56 was detected only in reactor sera, and was generated only by agents known preferentially to activate the properdin pathway. Elution of C56 from zymosan in hypertonic salt solutions proved to be a convenient step in the partial purification of large amounts of this haemolytically active bimolecular complex.

Binding Sites↗
PubMed1975

Studies on the inhibition of C56-initiated lysis (reactive lysis). III. Characterization of the inhibitory activity C567-INH and its mode of action.

An activity in serum which inhibits reactive lysis has recently been shown to do so by preventing the attachment of C567 complexes to cells, and hence has been designated C567-INH. This report describes certain physiochemical characteristics of the inhibitory activity. It behaves as a heat-stable pseudoglobulin, soluble in 20 per cent Na2SO4, and having alpha1 mobility on Pevikon block electrophoresis. It is excluded from CM cellulose at pH 6-0, RSC Equals 0.007 M, is retained by an XM-100 membrane and is heterogenous on Sephadex G-200, eluting in at least two peaks. The combined active materials from the Sephadex column elute from DE-52 in at least four peaks. The mechanism of action of material from each of these four peaks is shown to involve prevention of attachment of C567 complexes to membranes, and this is shown to involve an effect on C567 complexes in solution rather than an effect on the membrane. A less dramatic effect on the lysis of EC567 by limited quanities of C8 and C9 can be demonstrated. Haemolytic studies using cell-bound C567 suggest that the interaction of C567-INH with C567 involves a loose reversible association. It is therefore postulated that C567-INH inhibits reactive lysis primarily by reversibly associating with the nascent C567 complex in solution, increasing its bulk and decreasing its diffusion capacity so that it is unable to reach a cell membrane before its haemolytic potential decays.

Animals↗
PubMed1975

Studies on the inhibition of C56-induced lysis (reactive lysis). VI. Modulation of C56-induced lysis polyanions and polycations.

Multiple polyanions and polycations were tested for their ability to influence formation of EC567 from C56, C7, and sheep erythrocytes. Six of 11 polyanions tested, including polyanethol sulfonate, heparin, and dextran sulfate, inhibited this reaction. By contrast, polycations (five or seven tested), including polybrene, protamine, and polyornithine, potentiated formation of EC567. The inhibition was similar to that previously described for anionic serum factors termed C567-INH, while the potentiation seemed to involve neutralization of serum C567-INH. Thus, this step of the complement attack mechanisms seems amenable to modulation by certain polyelectrolytes, and may thereby be susceptible to pharmacologic manipulation.

Animals↗
PubMed1975

Studies on the inhibition of C56-initiated lysis (reactive lysis). V. The roleof C567-INH in the regulation of complement-dependent haemolysis initiated by cobravenom factor.

Activation of the alternative pathway of complement by a factor from cobra venom (CVF) can lead to lysis of unsensitized erythrocytes (E) of some species. In these studies we observed that alterations in CVF-induced lysis could be produced by manipulation of C567-INH, a naturally occurring inhibitory activity which acts on fluid phase C567 complexes. Venom lysis of sheep and guinea-pig E was markedly inhibited by serum fractions having C567-INH activity. Microgram quantities of poly-L-lysine (PLL), molecular weight 180,000, a polycation which is a functional antagonist to C567-INH in serum, potentiated CVF lysis of sheep and guinea-pig E, and permitted the lysis of human E, which are otherwise not suscepticle to CVF lysis. The potentiation of venom lysis by PLL seemed not to be due to alterations in the target cell membrane; furthermore, it in turn was reversed by substances with C567-INH activity. This suggests that the generation of fluid phase C567 complexes contributes to the CVF-induced lysis of erythrocytes of these species, and that the haemolytic potential of fluid phase C567 generated during alternative pathway activation by this means is regulated by C567-INH.

Ammonium Sulfate↗
PubMed1975

Complement activation by interaction of polyanions and polycations. I. Heparin-protamine induced consumption of complement.

Interactions of heparin and protamine in fresh human serum, in amounts far below those required for complement depletion by either agent alone, were found to induce virtually complete depletion of total hemolytic complement activity. This depletion was dependent on time, temperature, pH, divalent cations, and serum concentration. The predominant complement component hemolytic activity depleted was C1; under appropriate reaction conditions C4 and C2 were depleted as well. Equivalent amounts of heparin along induced lesser but substantial depletion of C3-9, whereas equivalent amounts of protamine had no effect upon complement component activities. We conclude that interaction of heparin with protamine, like interaction of antibody with antigen, markedly enhances its ability to interact with the first component of complement and activate the classical complement pathway. It is suggested that complement activation by interactions between certain polyanions and polycations, like interactions between antigens and antibodies, may have a role in the initiation of inflammatory reactions.

Adult↗
PubMed1975

Studies of the inhibition of C56-initiated lysis (reactive lysis). IV. Antagonism of the inhibitory activity c567-INH by poly-L-lysine.

The stable intermediate complex C56 can initiate the lysis (reactive lysis) of unsensitized erythrocytes (E) by the membrane attack machanism of complement. Certain serum constituents designated C567-INH inhibit reactive lysis by preventing the C567 complex, once formed, from attaching to a membrane surface. It is shown here that microgram quantities of poly-L-lysine (PLL), a synthetic polycation of molecular weight 180,000, can reverse the effests of C567-INH, and thereby potentiate formation of EC567 by erythrocytes, C56 and C7 in whole serum. Erythrocytes exposed to PLL in a preincubation step did not show either increased susceptibility to C567 or resistance to C567-INH, and reversal of C567-IHN by given amounts of PLL was not diminished as cell concentrations were greatly increased, indicating that the effect of PLL was predominantly directed against fluid phase rather than against erythrocyte membrane substrates. The effects of PLL and C567-INH were quantitatively reciprocal. Thus, PLL-induced potentiation of C56-induced lysis is a solute effect which seems to involve direct neutralization of naturally occurring serum inhibitors of the C567 trimolecular complex of complement. The use of PLL thus provides a suitable antagonist for C567-INH in reaction mixtures, and allows evaluation of the role of C567 and C567-INH in a variety of situations involving C-mediated lysis.

Alpha-Globulins↗
PubMed1974

Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera.

Protamine sulfate was found to consume large amounts of C selectively during preincubation with sera of individuals in the "acute phase". Marked depletion of C1, C4, and C2 with minimal, if any, depletion of C3-9, was observed. The consumption was time and temperature dependent, occurring most rapidly and extensively at 37 degrees C, 0.10 M relative salt concentration and pH 7.5-8.0; it required calcium ions. It was mediated by a heat-stable nondialyzable factor which separated with C-reactive protein (CRP) during fractionation and purification, correlated with serum CRP levels, and, like other known reactivities of CRP, was inhibited by phosphoryl choline. Preparations of CRP purified either from serum or ascites resulted in consumption of large amounts of C1, C4, and C2 when preincubated with normal serum and protamine. We conclude that CRP is a potent activator of the C system at the level of C1, and that polycations such as protamine sulfate are substrates of CRP which can bring about this activation. It seems not unlikely that one role of CRP in health and disease involves its ability to interact with the C system.

Animals↗