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Biomedical subjects

A E Stitzel

Publications and source records attributed to A E Stitzel.

32 records · Page 2Linked to original sources
PubMed1976

Activation of the alternative pathway of complement in childhood acute lymphoblastic leukemia.

Sequential studies in children with acute lymphoblastic leukemia have demonstrated that at diagnosis or relapse there is defective utilization of complement by the alternative pathway. Thus, the sera of 17/18 patients fail to completely consume C3 to C9 when incubated with zymosan or cobra venom factor (CoF). This underutilization is due to a specific inhibitor of C3 activation which has been partially isolated. By remission, the inhibotor disappears and the CoF and zymosan assays return to normal. In addition, serum levels of C3 and factor B are elevated at the time of diagnosis or relapse but fall to below 3 S.D. from the mean in nearly 60 per cent of the cases during induction therapy. Similarly, serum C4 levels which are normal at diagnosis fall to less that 3 S.D. from the mean in 7/12 cases during treatment. Low C3 levels correlate well with factor B values, suggesting that if C3 to C9 are utilized after the inhibitor has been eliminated, such utilization occurs primarily through the alternative pathway. Presumably, as illustrated by the low C4 levels, this activity is mediated by the ampliciation loop of the alternative pathway involving classical pathway generation of C3b.

Child↗
PubMed1975

Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test.

The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidative metabolism. The oxidation of glucose-1-14-C by supernatant prepared from selectively depleted sera indicated that the neutrophil-stimulating factor(s) was generated through the alternate pathway of complement activation. The possibility that inulun had been ingested as a particle was ruled out by light microscopy and radiolabeling studies. The failure of neutrophils stimulated by the serum-inulun supernatants to migrate after exposure to a chemotactic agent suggested that the site of neutrophil-complement interaction was on the cell membrane. It is concluded from these results that biologically active fragments generated through the alternative pathway of complement activation can stimulate neutrophil metabolism in the absence of phagocytosis. Interaction of such fragments with circulating neutrophils in vivo and the subsequent metabolic activation of these cells is one explanation for the spontaneous reduction of nitroblue tetrazolium dye in vitro by neutrophils from patients with certain infections and inflammatory disorders.

Absorption↗
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↗
PubMedDate not supplied

Complement changes during granulocyte adhesion.

The granulocyte adherence assay was investigated as a potential in vitro model of filtration leukapheresis to study the effects produced on the complement system by passing anticoagulated blood through columns packed with nylon fibers. Complement activation per se was found not to be a prerequisite for the simple attachment of neutrophils to nylon fibers in this system, because none of the complement components studied were consumed in blood freely flowing through or incubated within adherence columns. Moreover, concentrations of the B antigenic determinant of C3 were unchanged, an indication that this pivotal component had not been cleaved. Although not required for adherence, complement activation is probably initiated by the process of neutrophil attachment, because chemotactic activity was generated. The precise nature of this activity was not identified, but information from previous studies of filtration leukapheresis and granulocyte adherence suggests the possibility of complement origin.

Cell Adhesion↗
PubMedDate not supplied

On the origin and control of C3NeF.

Nephritic factors are a relatively recent addition to the growing list of autoantibodies. C3NeF was the first of these to be described and acts by stabilizing the alternative pathway C3/C5 convertase. IgG and IgM C3NeF as well as anti-idiotypic antibody to C3NeF, may be found in normal individuals at all ages. In addition, internal image anti-idiotypic antibody can also be demonstrated in patients with glomerulonephritis. Thus, C3NeF appears to fulfill all of the criteria for being a product of normal B-cell function. The potential dysregulation of this process and the role of C3NeF in glomerulonephritis remains theoretical at best.

Autoantibodies↗