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F J DIXON

Publications and source records attributed to F J DIXON.

At least 19 recordsLinked to original sources
PubMed1965

A ROLE OF POLYMORPHONUCLEAR LEUKOCYTES AND COMPLEMENT IN NEPHROTOXIC NEPHRITIS.

In acute nephrotoxic nephritis, polymorphonuclear leukocytes (polymorphs) accumulated in large numbers in the glomeruli in the first 12 hours. The endothelial cells were dislodged by the polymorphs which then came to lie immediately adjacent to the glomerular basement membranes. Ultrastructural changes in neither polymorphs nor basement membranes were observed. Depletion of polymorphs in both rats and rabbits prevented the development of proteinuria. This occurred when doses of nephrotoxic globulin were employed that produced proteinurias of as much as 1800 mg/kg/24 hours in intact rabbits, or enough to yield near maximal immediate proteinuria in intact rats. In addition, measurable glomerular damage was frequently averted until the onset of the secondary stage of NTN. Controls indicated that the polymorph depleted animals exhibited minimal non-specific changes in the blood, that the ability of their vascular beds to react to stimuli was not affected, and that deposition of nephrotoxic antibody and C' in the glomeruli was not inhibited. Elimination of polymorphs from the circulation was only partially effective in preventing glomerular damage when large doses of nephrotoxic globulin were used. This indicated that under these circumstances, a polymorph independent glomerular injury may also take place in first stage nephrotoxic nephritis. An indirect role of C', i.e., the accumulation of polymorphs, in bringing about glomerular injury in first stage nephrotoxic nephritis was apparent. When rabbit nephrotoxic globulin was injected into rats depleted of C', or when duck nephrotoxic globulin that fixed C' poorly was injected into normal rats, C' failed to bind with the antibody along glomerular basement membranes and polymorphs did not accumulate.

Animals↗
PubMed1965

METABOLISM AND FUNCTION OF GAMMA GLOBULIN IN ALEUTIAN DISEASE OF MINK.

Aleutian disease-affected mink, which are markedly hypergammaglobulinemic, show a decreased half-life of the serum gamma globulin indicating that the hyperglobulinemia is due to increased production. No evidence that the gamma globulin was antibody to the infectious agent, to autologous or isologous tissues, or to antigens the animal was responding to prior to development of the disease was obtained. The increased gamma globulin was found to be of the 6.4S variety, and gamma globulin containing protein-protein complexes of 9S to 17S and 22S to 25S classes were observed in serums of affected mink. The findings are most consistent with the Aleutian disease virus acting as a direct and somewhat selective stimulus to plasma cell proliferation. There is no evidence that the arterial and glomerular lesions of Aleutian disease have an immunologic pathogenesis. It seems possible that these vascular changes may be directly caused by the viral agent, or may be the result of the increased gamma globulin levels.

Aleutian Mink Disease↗
PubMed1965

EXPERIMENTAL GLOMERULONEPHRITIS. V. STUDIES ON THE INTERACTION OF NEPHROTOXIC ANTIBODIES WITH TISSUE OF THE RAT.

A direct correlation between the amount of kidney-fixing antibody and the degree of associated renal injury was demonstrated for rabbit and duck nephrotoxic antibodies. No evidence for a qualitative difference among nephrotoxic antibodies of a given type was obtained. It appeared that duck nephrotoxic antibody was directed against a wider spectrum of rat renal antigens than was rabbit nephrotoxic antibody. In order to produce immediate proteinuria an amount of rabbit or duck gamma-2 kidney-fixing antibody capable of occupying approximately 45 per cent or more of the capillary filtration surface was needed. For immediate proteinuria an amount of rabbit gamma-2 kidney-fixing antibody capable of reacting with more than one-half of the available antigenic sites was needed. Less than twice that amount of rabbit antibody completely saturated available antigenic sites in the kidney. Virtually all nephrotoxic antibodies in hyperimmune rabbit nephrotoxic sera were of the gamma-2 variety while nephrotoxic antibodies in comparable duck nephrotoxic sera were found in gamma-2 (with 5.8 and 7.4S sedimentation coefficients) and gamma-1M fractions. Gamma-1M duck nephrotoxic antibody was 60 times more potent a nephritogen than gamma-2 duck nephrotoxic antibody on a molecular basis. Mercaptoethanol abolished the nephrotoxicity of gamma-1M duck antibody and reduced that of gamma-2 duck antibodies but had no effect on rabbit gamma-2. In no case did mercaptoethanol treatment have an effect on the kidney-fixing properties of the antibodies involved. After injection of nephrotoxic antibodies there appeared to be a prompt fixation of a majority of the antibody to tissue antigens primarily in the kidney. However, a small amount of potentially kidney-fixing antibody remained in the circulation for a considerable period apparently reflecting a dissociation of less avid antibodies with an equilibrium between fixed and free antibody. The role of this more easily dissociable antibody in the progression of nephrotoxic nephritis is not certain but it is possible that it could play a role in the early progression of the disease.

Animals↗
PubMed1965

EXPERIMENTAL GLOMERULONEPHRITIS. VI. THE AUTOLOGOUS PHASE OF NEPHROTOXIC SERUM NEPHRITIS.

Nephrotoxic serum nephritis was studied in rats receiving variable amounts of kidney-fixing antibody and active or passive immunization to the heterologous gamma globulin of the species supplying the nephrotoxic antibody. Rats injected with a moderate to a large amount of kidney-fixing antibody (180 to 380 microg) and immunized to the heterologous gamma globulin developed a more severe nephritis than rats receiving similar amounts of antibody without further immunization. Rats injected with minimal amounts of kidney-fixing antibody (2 to 45 microg) and immunized to the heterologous gamma globulin developed a moderate nephritis in contrast to rats receiving similar amounts of antibody without further immunizations which showed no evidence of renal injury. In the rats receiving small doses of kidney-fixing antibody and immunization to the heterologous gamma globulin a lag period existed between the appearance of circulating antibody and kidney-fixed host antibodies and the appearance of renal injury. This delay apparently reflects the need for a continuing antigen-antibody reaction for some time in order to produce detectable injury with the small amounts of reactants involved. From these data it appears that, in the presence of excess circulating antibody, antigens occupying at most a few per cent of the glomerular capillary surface can provide an antigen-antibody interaction which will over a period of time cause detectable morphological and functional alterations of the glomerulus.

Animals↗
PubMed1964

EXPERIMENTAL GLOMERULONEPHRITIS. IV. PARTICIPATION OF COMPLEMENT IN NEPHROTOXIC NEPHRITIS.

Rats with nephrotoxic serum nephritis may show fixation of complement (C') in the glomeruli during two periods. The first period occurs immediately after the injection of the antisera and extends until the host response occurs. The second period is related to the deposit of rat gamma globulin in the glomeruli presumably occurring at the time of the immune response to the heterologous nephrotoxic serum (NTS). This second period terminates about 2 to 3 weeks after injection of NTS, presumably at the time the rat stops making antibodies to the nephrotoxic gamma globulin fixed in the glomeruli. After this period, the glomerular lesion is incapable of fixing detectable amounts of circulating C' unless the antibody response to the heterologous globulin is reactivated. The immunological events which take place in the initial 2 to 3 week period appear to produce a permanent and irreparable lesion in the glomeruli leading to chronic nephritis. Rabbit NTS produces fixation of rat C' during both periods. Duck NTS shows no detectable fixation of rat C' until rat gamma globulin fixes in the glomeruli at the time of the host immune response to the heterologous nephrotoxic gamma globulin. Decomplementation of rats injected with rabbit NTS produces an amelioration of the initial period of nephrotoxic serum nephritis. The fixation of C' in the glomerular lesions was studied with the use of fluorescent antibody methods. The detection of host beta-1C globulin and gamma globulin in the glomerulus pointed to an immune reaction but not necessarily an active one. The tissue C' fixation test using kidney slices and guinea pig C' proved to be a more sensitive method of detecting tissue reactants capable of fixing C', but its relationship to in vivo events is not certain.

Animals↗
PubMed1963

Experimental glomerulonephritis. II. Immunologic events in the pathogenesis of nephrotoxic serum nephritis in the rat.

The primary phase of nephrotoxic serum nephritis produced by rabbit nephrotoxic serum appears to be dependent to a great extent, but not completely, upon the participation of serum complement. On the other hand, duck nephrotoxic serum produces its primary renal injury without detectable utilization of or dependence upon serum complement. The secondary phase of nephrotoxic serum nephritis appears to be largely or entirely dependent upon the host's antibody response to the heterologous gamma globulin fixed in the glomeruli. No evidence could be obtained for the existence of an autoimmune antikidney response by the host in this experimental model.

Animals↗
PubMed1963

Enhancement of antibody formation by whole body x-radiation.

Enhancement and acceleration of the antibody response can be achieved in some situations with large, cytotoxic doses of whole body x-radiation given after antigenic stimulation. The timing of radiation is critical and varies with the kind and physical form of the antigen. It is postulated that the x-radiation depletes the cells of the lymphoid tissues just prior to the rapid proliferation of the antigen stimulated cells. In this situation those surviving cells which are stimulated by antigen multiply more rapidly than their non-stimulated counterparts and disproportionately repopulate the depleted lymphoid tissues. Whether the x-radiation produces other effects contributing to the multiplication of the antibody forming cells was not determined. It appears that x-radiation produces its enhancement of antibody formation by means different from those operating in endotoxin and colchicine induced enhancement.

Animals↗
PubMed1962

The metabolism of serum proteins in the hen and chick and secretion of serum proteins by the ovary of the hen.

In the chicken, serum gamma globulin (CGG) is preferentially transferred by the follicular epithelium of the ovary to the developing ova. The concentration of gamma globulin in the yolk of the unfertilized egg is many times the concentration of chicken serum albumin (CSA). This transfer occurs largely during the 4 to 5 days preceding ovulation when the growth of the ovum is most rapid. Thus, in the chicken, the follicular epithelium of the ovary serves the same purpose in the passive immunization of offspring as does the acinar epithelium of the udder in ungulates and the extraembryonic membranes in rabbits and man. The amount of gamma globulin synthesis by the chick is low during the first 2 weeks of life and is associated with low levels of serum gamma globulin. By the end of the 1st month of life, the level of serum gamma globulin increases, presumably reflecting an increased rate of synthesis. In the adult hens the half-life of I(131)-labeled CSA is 66 hours and that of I(131)-labeled CGG, 35 hours, while in the newly hatched chick for I(131)-labeled CSA it is 42 hours and for I(131)-labeled CGG, 72 hours. Thus, this species shows a gamma globulin sparing in the first days of life, as do most mammalian species.

Animals↗