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N C Davis

Publications and source records attributed to N C Davis.

At least 55 records · Page 3Linked to original sources
PubMed1971

The antigenic and molecular alterations of C3 in the fluid phase during an immune reaction in normal human serum. Demonstration of a new conversion product, C3x.

During the reaction of an immune precipitate with fresh human serum, C3 undergoes a number of molecular alterations with the formation of conversion products differing from those obtained when purified components react. Those products which remain in the fluid phase, the subject of the present paper, have been identified by their reaction with monospecific antisera to the three antigenic determinants of C3, A, B, and D, after electrophoresis in agar or polyacrylamide gel. When purified C3 reacts with EAC1,4,2, C3i is found in the fluid phase. C3i, a loose complex of C3a and C3b, is in a conformational state whereby only the A and D antigens, present on its C3b portion, will consume antibody. The B antigen, present on the C3a portion of C3i, is unavailable for combination with antibody until C3i dissociates. In the fluid phase of the reaction of an immune precipitate with whole serum, C3i, C3a, and C3b, formed when purified components react, cannot be found. Instead the end products of the reaction appear to be C3c, which contains the A antigen, and C3d, which contains the D antigen. C3c and C3d are similar to the beta1A and alpha2D produced by the aging of serum but differ in their mobilities in acrylamide gel and in agar. The C3c and C3d generated by an immune precipitate also differ slightly from the C3c and C3d produced by the reaction of trypsin with C3 in whole human serum. As human serum reacts with an immune complex, native C3 appears to undergo a primary alteration before conversion. This alteration results in a molecular species of C3 which is labile at 56 degrees C for 30 min, fails to expose additional A and D antigenic sites upon aging, and which forms beta1A and C3d rather than beta1A and alpha2D during aging. In addition to this altered form of native C3, a new conversion product, C3x, is formed as whole serum reacts with an immune complex. C3x is not found in systems utilizing pure complement components. C3x is like C3 in that it bears all three antigenic determinants but differs in that it has a slightly faster mobility in polyacrylamide gel than does native C3. C3x is not only found in the fluid phase but is also bound to the immune precipitate. Finally, the fluid-phase kinetics of each of the antigens of C3 have been determined as normal human serum reacts with an immune precipitate. These illustrate that nearly the entire population of native C3 molecules undergoes conversion rapidly as manifested by the disappearance of the B antigen from the fluid phase. Moreover, the kinetics of the fluid-phase A and D antigens reflect that the conversion of C3 in serum is quantitatively not the same as when purified C3 reacts with C4,2.

Adult↗
PubMed1971

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

Adolescent↗
PubMed1970

Characteristics of a non-complement-dependent C3-reactive complex formed form factors in nephritic and normal serum.

When serum from a patient with membrano-proliferative glomerulonephritis and normal serum are mixed at 37 degrees C, C3 is rapidly broken down to two more rapidly migrating components. In the mixture, a heat-labile pseudoglobulin, designated as the C3 nephritic factor or C3NeF, reacts with a pseudogolbulin in the normal serum, designated as cofactor, to form a C3 inactivator. By analogy with the cobra venom factor, the C3 inactivator is most likely a complex of the nephritic factor and cofactor. The complex has been designated as the C3 lytic nephritic factor or C3LyNeF. The reaction which results in the Formation of C3LyNeF requires the presence of Mg(++), is highly temperature sensitive but occurs very rapidly at 37 degrees C. In 20 min at 37 degrees C, C3LyNeF can break down over 80% of the C3 in a mixture of normal and nephritic serum. The two-step reaction which leads to C3 breakdown has an optimum pH ranging from 6.0 to 9.0. Experiments employing serum depleted of C4 and C2, as well as certain characteristics of the C3NeF system provide evidence that C3 breakdown with nephritic serum is not dependent on complement-inactivating immune complexes or on the action of convertase (C4, 2). Data relating rate of C3 breakdown to the concentrations of C3NeF, C3, and C3LyNeF in the reaction mixture are similar to those for the reaction of enzyme with substrate. The biological significance of C3LyNeF in the production of glomerular inflammation has not been established.

Antigen-Antibody Reactions↗
PubMed1969

Serum C'3 lytic system in patients with glomerulonephritis.

The serums of patients with hypocomplementemic glomerulonephritis contain a substance that combines with a normal serum cofactor in the presence of magnesium ion to specifically cleave the third component of complement. This lysis of C'3 is 80 to 90 percent complete in 20 minutes at 37 degrees C and pH 7. Neither the nephritic factor nor its cofactor is identifiable with the complement system.

Antigen-Antibody Reactions↗
PubMed1967

Evidence for in vivo breakdown of beta-10-globulin in hypocomplementemic glomerulonephritis.

Evidence has been obtained for the presence in vivo of alpha(2D)-globulin, a breakdown product of serum beta(1C)-globulin, in patients with acute and persistent hypocomplementemic glomerulonephritis. The protein has been identified by immunoelectrophoretic analysis, and the amounts present have been determined by direct measurement of specific antigenic determinants present on alpha(2D). beta(1A)-Globulin, another breakdown product of beta(1C)-globulin, may also be present in vivo in severely hypocomplementemic patients, but its levels are much lower than those of alpha(2D)-globulin.Alpha(2D)-globulin has been identified by immunoelectrophoretic analysis of fresh EDTA plasma from patients with hypocomplementemic nephritis as an arc in the alpha(2) region that shows a reaction of identity with the arc representing alpha(2D)-globulin produced by aged normal serum. beta(1A)-Globulin was not seen in these patterns. Measurement of specific antigenic determinants has been carried out in both fresh EDTA plasma and aged serum. In the fresh plasma, the concentration of D antigen, found on both beta(1C)- and alpha(2D)-globulins, has been related to that of B antigen, found only on beta(1C) and taken as a measure of the concentration of this protein. In the hypocomplementemic patients, the concentration of D antigen, in comparison to that of B, was greater than in the normal subjects. Similarly, in aged serum, the level of alpha(2D) was greater than would be expected from the amount of beta(1C) that had been broken down in vitro, measured by the concentration of beta(1A). Calculations indicated that the in vivo alpha(2D) level in severely hypocomplementemic patients ranged from 7.5 to 18% of that which would be found in a pool of aged normal serum in which beta(1C) is completely broken down. The levels tended to be lower in less severely hypocomplementemic patients, and none could be detected in normal plasma. Only small quantities of A and D antigens are detectable in the urine of patients with hypocomplementemic nephritis. The rate of excretion is about equal to that of the normal subject. The study indicates that the low serum levels of beta(1C)-globulin that may be present over long periods in patients with persistent hypocomplementemic glomerulonephritis can be ascribed, in part, to in vivo breakdown of this protein as a result of reaction with immune complexes. The contribution of beta(1C) deposition on immune complexes and of diminished synthesis to the depressed serum levels cannot be assessed by the present study.

Adult↗