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Biomedical subjects

D Carson

Publications and source records attributed to D Carson.

At least 55 records · Page 3Linked to original sources

Occurrence of two germline-related rheumatoid factor idiotypes in rheumatoid arthritis and in non-rheumatoid seropositive individuals.

Human rheumatoid factor (RF) paraproteins express two distinct light chain cross-reactive idiotypes defined by the monoclonal antibodies 17.109 and 6B6.6. These germline gene-related cross-reactive idiotypes are both carried on VK3 light chains and are each present on about one-third of IgM RF paraproteins. We assessed the degree to which these idiotypes are represented in polyclonal RFs. We used rheumatoid arthritis (RA) and non-RA RF-positive sera selected from a large cross-sectional population study (the Mini-Finland Health Survey), and sera from a community-based follow-up study of recent-onset RA patients from Heinola, Finland. In the Mini-Finland Health Survey, elevated levels of the 17.109 RF idiotype were seen in sera of 13% of the RA and 19% of the non-RA group; 6B6.6 RF was seen in 26% of the RA and 28% of the non-RA group. In sera of the Heinola follow-up study, 17.109 RF was seen in 12% initially, but in only 3% at 8 years. Similarly, 6B6.6 RF was detected in 25% initially, but in only 7% at 8 years. Ten sera positive for RF prior to the onset of clinical RA were identified from individuals of a second large population study from Finland (North Karelia project); two of these sera exhibited the 6B6.6 idiotype; none exhibited the 17.109 idiotype. The data are consistent with the concept that these germline gene-related cross-reactive RF idiotypes occur frequently in the polyclonal RF of non-RA as well as RA sera, and that in RA the idiotypes may sometimes be reduced or lost as a consequence of somatic diversification of the RF through somatic mutation, usage of new germline genes, or both.

Arthritis, Rheumatoid↗

Evidence that secondary rat Schwann cells in culture maintain their differentiated phenotype.

Schwann cells, on receiving the correct signal, will encircle an axon and wrap it with a myelin sheath. To begin examining some of the mechanisms underlying the process of myelination in vitro, we isolated Schwann cells from the sciatic nerves of neonatal rats and generated large cell populations with cholera toxin. The immunological and biochemical properties of these secondary Schwann cells were characterized after five to seven passages in the absence of axonal contact. These cells continued to express antigens found in both myelinating (P0 and 2',3'-cyclic nucleotide phosphohydrolase) and nonmyelinating cells in vivo (A5E3 and glial fibrillary acidic protein) in addition to the markers common to both types of cells (Ran-1, 217c, S-100, and laminin). Biochemical analyses showed that these cells synthesize the very-long-chain fatty acids (22-26 carbon atoms) found in myelin membranes. Moreover, the enzymes required for the synthesis of myelin glycolipids (including sphingosine acyltransferase, UDP-galactose:ceramide galactosyltransferase, and cerebroside sulfotransferase) were still active, and metabolic labeling studies showed that galactocerebroside and sulfatide were synthesized even though the galactocerebroside pool was insufficient to be detected by immunostaining. Secondary Schwann cells also synthesized four species of myelin basic protein and the major structural glycoprotein in myelin, P0. The pathway necessary for glycosylation of P0 protein remained active, and an analysis of the oligosaccharide chain revealed that approximately 70% was processed to a complex form. In summary, we found that secondary Schwann cells still express most of the immunological markers of differentiated cells and continue to synthesize low levels of myelin components. Therefore, Schwann cells do not dedifferentiate in culture, as previously believed.

Animals↗

Cerebral oedema complicating diabetic ketoacidosis.

Signs of raised intracranial pressure (ICP) developed during treatment of diabetic ketoacidosis in a young child. A CT scan revealed cerebral oedema and direct measurement confirmed elevated ICP. Aggressive treatment was successful in maintaining cerebral perfusion pressure. The child survived with mild handicap in contrast to the poor outcome of previous reports.

Brain Edema↗

Structural and idiotypic characterization of the L chains of human IgM autoantibodies with different specificities.

We have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1. JK and CK genes did not show the same pattern of restriction. There is a good correlation between the amino acid sequence and the presence of the kIIIb marker. The idiotypic marker PSL2 was present in 34 out of 35 kIIIb L chains analyzed (97%) and the PSL3 in 27 (80%). Moreover, the hydrophilicity and antigenic profiles of these L chains corroborate the presence of the epitopes detected by the anti-CRI. These results demonstrate a restricted selection of the Vk genes used by a family of self reacting proteins, and an unusual evolutionary conservation of the idiotypic structure that may be involved in the network regulation.

Agglutinins↗

Pituitary function studies in a case of mild Hunter's syndrome (MPS IIB).

Pituitary function studies were performed in a patient with mild Hunter's syndrome (mucopolysaccharidosis type IIB, MPS IIB) in order to exclude growth hormone deficiency as a possible contributing cause of his short stature. The results indicated that anterior pituitary function and, in particular, growth hormone secretion was normal. The most likely explanation for the short stature is an osseous growth plate disturbance with infiltration of the epiphyses by mucopolysaccharides.

Adolescent↗

Alternative measures of diarrhoeal morbidity and their association with social and environmental factors in urban children in The Gambia.

Diarrhoeal morbidity was studied during a 15-week period of the rainy season in 244 children aged 6 to 35 months in an urban Gambian community. The average prevalence of diarrhoea was 12.0% and the mean number of episodes per child varied between 2.4 and 2.9 depending on the definition of an episode. The number of chronic episodes lasting 14 d or more was tripled when 7 rather than one diarrhoea-free days were required to define a new episode. Neither prevalence nor the number of episodes varied significantly with age or sex. There was little association between the social and environmental characteristics of the children and diarrhoeal morbidity. The implications of using differing measures of diarrhoeal morbidity are discussed.

Child, Preschool↗