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Biomedical subjects

C Horgan

Publications and source records attributed to C Horgan.

26 records · Page 2Linked to original sources

Quantitative determination of anti-dsDNA antibodies and antibody/dsDNA stoichiometries in prepared, soluble complement-fixing antibody/dsDNA immune complexes.

We have investigated quantitatively the complement-mediated binding of prepared, soluble 125I-7S IgG antibody/3H-dsDNA immune complexes to human red blood cells (RBCs). We have performed these studies by using a detailed modification of the RBC-CF assay [Pedersen et al., J. Immun. Meth. 38, 269-280 (1980)] which now allows for the simultaneous measurement of both 3H-DNA and 125I-binding to the cells. Our results indicate that, in the case of three SLE patients, their anti-dsDNA antibody titers are sufficiently high that a small fraction of their 125I-7S IgG antibodies (ca 0.1-0.2%) can be identified as specifically anti-dsDNA. We have also used an indirect method (with 125I-labelled rabbit anti-human IgG) for the determination of IgG anti-dsDNA antibodies in complement-fixing antibody/dsDNA immune complexes that bind to RBCs, and the results of these measurements are in reasonable agreement with the direct binding experiments. These studies have also allowed us to estimate the antibody/DNA stoichiometries in complement-fixing immune complexes. The results of these experiments may provide a useful standard for the analysis of monoclonal anti-dsDNA antibodies.

Antibodies, Antinuclear↗

The kinetics of [3H]-dsDNA/anti-DNA immune complex formation, binding by red blood cells, and release into serum: effect of DNA molecular weight and conditions of antibody excess.

[3H]dsDNA/anti-DNA immune complexes (IC) formed, fixed complement, and bound rapidly to red blood cells (RBC) in whole blood (less than 5 min), but were released from the cells more slowly. The rate of release was dependent on both the antibody:DNA ratio and the m.w. of the DNA in the complex. For example, complexes formed with high m.w. DNA (6 X 10(6) daltons) were released more slowly (t1/2 = 60 min) than complexes formed with lower m.w. DNA (2 to 6 X 10(5) daltons, t1/2 = 15 to 20 min). The [3H]dsDNA/anti-DNA complexes, which were released from the cells as intact antigen/antibody/complement complexes, did not rebind to RBC, but did bind to Raji cells and could be precipitated by monoclonal antibody to C3d. When these released IC (RIC) containing high m.w. DNA were incubated with additional anti-DNA antibody and fresh complement, they rebound to RBC. However, RIC containing lower m.w. DNA (5 X 10(5) daltons) did not rebind to RBC under the same conditions. These data suggest that IC containing high m.w. DNA bind to and remain bound to RBC more effectively than IC containing lower m.w. DNA, and thus may be more easily cleared from the circulation by the RBC IC clearance mechanism. Thus, the size of the DNA in the IC may be a significant factor in the pathogenicity of DNA/anti-DNA complexes in SLE.

Antibodies, Antinuclear↗

Quantitative analyses of complement fixation in three immune complex systems.

The quantitative interaction of three different immune complex systems with complement has been investigated. dsDNA/anti-DNA, heat-aggregated IgG subfractions, and human IgG/rabbit anti-human IgG complexes were tested for their ability to consume complement (immune haemolysis assay) and to bind to red blood cells in a complement-mediated reaction (the RBC-CF assay). Our results indicate that some physical and immunological properties of the dsDNA/anti-DNA immune complex systems are significantly different from those of immune complexes that involve more common globular protein antigens. This difference in properties may help explain the role of dsDNA/anti-DNA immune complexes in systemic lupus erythematosus pathogenesis.

Animals↗

Decreased complement mediated binding of antibody/3H-dsDNA immune complexes to the red blood cells of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies.

The complement mediated binding of prepared antibody/3H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.

Adolescent↗

Growth and reproduction of two species of Akodon and their hybrids.

Growth and reproduction of Akodon molinae (A.m.), A. dolores (A.d.) (Rodentia: Cricetidae), and their hybrids are described. A.d. showed less fertility under animal room conditions, fewer "successful" matings, similar litter sizes, and an altered sex proportion as compared to A.m.; A.d. ovulatory index is supposed to be higher than mean litter size. X-linked lethal gene(s) and chromosome polymorphisms are possible causes of these variations. Interspecific crosses showed a marked seasonal (summer) tendency in parturitions. Intraspecific matings also produced young during winter. F1 hybrids showed a reversed tendency, while F2 matings returned to the parental pattern. A.d. male X A.m. female and F1 crosses presented larger litter sizes than the other pairings. A.m. exhibited sexual differences in weight after 60 days of age. A.d. and F1 hybrids did not show significant differences in weight of both sexes at any age. A.m. males and females were heavier than A.d. individuals except 12 months after birth. F1 hybrids born to A.m. male were heavier at birth than the A.d. female s interspecific offspring, and may be interpreted as a maternal influence of the A.m. females. Hybrids were heavier than their parents at birth and some of them were also heavier at 21 days, and probably is due to pseudoheterosis. The comparison of body measurements between sexes of both species did not give conclusive results. A.m. females were larger than females of A.d. Males of both species showed similar total lengths; A.m. males had larger body lengths and shorter tails. Body measurements were not related to weight variations. However, differences in weight and measurements between sexes appeared simultaneously at 2-6 months. This probably reflected the attainment of maturity.

Animals↗

The complement-mediated binding of soluble antibody/dsDNA immune complexes to human neutrophils.

The complement-mediated binding of soluble antibody/3H-dsDNA immune complexes (prepared in vitro) to human polymorphonuclear leukocytes (PMN) has been investigated quantitatively. Studies with isolated complement components in conjunction with experiments on the binding of these complexes to human red blood cells suggest that the binding to both cell types is mediated predominantly by CR1 (C4b-C3b) receptors but that CR3 (iC3b or C3d-g) receptors may play a role in binding to PMN but probably not to RBC. Our results also indicate that under the standard conditions of these assays (37 degrees C, 20 to 40 min incubations) there is no significant internalization of the soluble antibody/dsDNA immune complexes after they are bound by the PMN.

Antigen-Antibody Complex↗

Do individuals with substance abuse diagnoses incur higher charges than individuals with other chronic conditions?

Concerns about high costs have led to limits on the services covered by most insurance plans for substance abuse treatment. But, the commonly used comparison group for cost analyses, all enrollees in a health-care plan, may not be appropriate because addiction is a chronic condition. Therefore, to determine whether substance abusers incur higher charges than patients with other serious chronic conditions, we used health insurance information for employees and dependents over 3 years (1989 to 1991) for two firms with a total of almost 40,000 employees to do alternate comparisons. We compared average annual charges for patients with the following diagnoses: substance abuse, substance abuse with mental illness, arthritis, asthma, and diabetes. Patients who undergo treatment for abusing alcohol, drugs, or both often (but not always) incur higher charges than people with other chronic conditions. Clear differences in average charges emerge between patients with and without mental health claims.

Adult↗