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Biomedical subjects

R I Carr

Publications and source records attributed to R I Carr.

At least 55 records · Page 3Linked to original sources

A naturally occurring antibody in New Zealand mice cytotoxic to dissociated cerebellar cells.

A spontaneously occurring antibody cytotoxic to dissociated cells of the neonate mouse cerebellum was found in the sera of some New Zealand (NZ) mice. No significant activity was found in the sera of six non-autoimmune mouse strains. The degree of cytotoxicity was similar towards both allogeneic and syngeneic cells. Absorption of the cytotoxic sera with brain and kidney homogenates removed the reactivity, while liver removed less reactivity. Absorptions with thymocytes and several other tissue homogenates and cells had no effect on the cytotoxicity levels, nor was there a correlation between the levels of thymocytotoxicity and cerebellar cell cytotoxicity. The antibody cytotoxic for cerebellar cells could not be demonstrated in the cerebrospinal fluid (CSF) of any mice examined, including a mouse with high serum cytotoxic levels. Gel filtration of reactive sera indicated that the antibody is of the IgM class.

Animals↗

A study of serum antibodies to isolated milk proteins and ovalbumin in infants and children.

Serum antibodies to cow milk proteins and ovalbumin were measured quantitatively. Food hypersensitivity of the immediate type was determined to be present or absent by skin tests and double-blind food challenges. Elevated levels of antibodies to milk proteins in sera characteristic of infants fed cow milk were found to decline with age, so that sera from children who were 6 to 15 years of age (inclusive), not hypersensitive to food, had significantly lower levels than the infants. In contrast, sera from age-matched children, who were shown to have hypersensitivity to some food, were found to have levels of antibodies to milk proteins as elevated as in infancy. Hypersensitivity was not necessarily to milk but often to some other food. This persistence of greater antibody production to milk throughout childhood in those hypersensitive to some food indicates a fundamental difference from those without hypersensitivity to food, either in permeability, in immunological reactivity of the gut or in development of immunological unresponsiveness. Implications for pathogenesis of clinical disorders are discussed.

Adolescent↗

The prognostic and therapeutic implications of DNA:anti-DNA immune complexes in systemic lupus erythematosus (SLE).

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.

Adolescent↗

Comparison of DNA binding in normal population, general hospital laboratory personnel, and personnel from laboratories studying SLE.

Sera from 18 of 56 individuals working in SLE laboratories bound more than 30 per cent of 0.1 mug of 125-I denatured calf thymus DNA, in an ammonium sulfate precipitation assay. Only two of 58 normal non-laboratory personnel and four of 40 sera from routine hospital laboratory personnel bound more than 30 per cent. Statistical analysis of these results with the Kolmogorov-Smirnov nonparametric test indicated this was a very significant difference (p less than .001). Using native DNA as a test antigen a similar pattern was seen, but it was not as clear cut. Part of this increased reactivity is heat labile. Further studies must be carried out before an adequate interpretation of these findings is possible.

Animals↗

Studies on the nature of circulating DNA in systemic lupus erythematosus (SLE).

The isolation and purification of DNA from the sera of patients with SLE is described. Buoyant density determinations of this DNA using CsCl gradients suggest in some cases that it may be of endogenous origin. DNA from the synovial fluid of an SLE patient with septic arthritis was also shown to have a buoyant density of human DNA as well as being of considerable size variation. In addition, this synovial fluid contained antibody to DNA and evidence of DNA:anti-DNA complexes, suggesting that immune complexes composed of human DNA and antibody may be involved in the pathogenesis of the arthritis. Also described are preliminary experiments characterizing the conformation of the DNA present in DNA:anti-DNA immune complexes.

Animals↗

Clinical studies on the significance of DNA:anti-DNA complexes in the systemic circulation and cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus.

Evidence has gradually accumulated that DNA antibodies play a pathogenic role in SLE in combination with DNA, as DNA: anti-DNA complexes, but until recently there was no direct assay for such complexes. By measuring DNA binding before and after DN'ase digestion, an indication of the amount of DNA complexes in biological fluids was obtained. This assay was used to examine sera from patients with SLE or non-SLE nephritis. DNA:anti-DNA complexes were detectable only in the circulation of patients with SLE, almost invariably with active nephritis. When a large series (50) of SLE patients were serially examined, similar results were found. Significant amounts of DNA:anti-DNA complexes were found in the circulation only during active CNS and/or renal lupus. Persistence of the complexes was associated with treatment resistance and increased morbidity and mortality. In addition, DNA:anti-DNA complexes were found in the CSF of a patient with CNS lupus.

Adult↗

DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera.

Antibody to DNA was measured before and after treatment of systemic lupus erythematosus (SLE) sera with bovine pancreatic deoxyribonuclease (DNase I). In 11 of 15 cases of SLE with active renal disease there was a significant increase in DNA-binding after DNase digestion, while no such increase was noted in inactive SLE, normal controls or in patients with nonlupus renal disease. The significant rise in DNA-binding after digestion indicated that DNA had bound in vivo to the anti-DNA in these sera. A striking correlation between the occurrence of these complexes and disease activity was shown. In eight cases of SLE nephritis where serial blood samples were obtained, the greatest increase in DNA-binding after DNase digestion occurred at the time of the severest renal disease. In addition, serum from a case of SLE with acute cerebritis but without evidence of renal disease also had a significant rise in binding during the acute phase. This assay provides proof of the existence of circulating DNA:anti-DNA complexes in some cases of SLE and can also be used to measure an apparently critical parameter of disease activity.

Antigen-Antibody Complex↗

Antibodies to polynucleotides: distribution in human serums.

Hemagglutination procedures were used to determine the distribution of antibodies to native DNA, single-stranded DNA, and double-stranded RNA. Antibodies to all three polynucleotides were found in a high percentage of the serums of patients with systemic lupus erythematosus. Antibodies to native DNA occurred almost exclusively in serums of patients in the active stages of systemic lupus erythematosus, whereas antibodies to single-stranded DNA were observed in the serums of patients with several diseases and of some normal individuals.

Antibody Formation↗