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Biomedical subjects

B A Cunningham

Publications and source records attributed to B A Cunningham.

135 records · Page 8Linked to original sources
PubMed1969

The covalent structure of an entire gammaG immunoglobulin molecule.

The complete amino acid sequence of a human gammaG1 immunoglobulin (Eu) has been determined and the arrangement of all of the disulfide bonds has been established. Comparison of the sequence with that of another myeloma protein (He) suggests that the variable regions of heavy and light chains are homologous and similar in length. The constant portion of the heavy chain contains three homology regions each of which is similar in size and homologous to the constant region of the light chain. Each variable region and each constant homology region contains one intrachain disulfide bond. The half-cystines participating in the interchain bonds are all clustered within a stretch of ten residues at the middle of the heavy chains.These data support the hypothesis that immunoglobulins evolved by gene duplication after early divergence of V genes, which specified antigen-binding functions, and C genes, which specified other functions of antibody molecules. Each polypeptide chain may therefore be specified by two genes, V and C, which are fused to form a single gene (translocation hypothesis). The internal homologies and symmetry of the molecule suggest that homology regions may have similar three-dimensional structures each consisting of a compact domain which contributes to at least one active site (domain hypothesis). Both hypotheses are in accord with the linear regional differential of function in antibody molecules.

Amino Acid Sequence↗
PubMed1969

Subgroups of amino acid sequences in the variable regions of immunoglobulin heavy chains.

The amino acid sequence of the first 133 residues of the heavy (gamma) chain from a human gammaG immunoglobulin (He) has been determined. This gamma-chain is identical in Gm type to that of protein Eu, the complete sequence of which has been reported. Comparison of the two sequences substantiates the previous suggestion that there are subgroups of variable regions of heavy chains. The variable region of Eu has been assigned to subgroup I and that of He to subgroup II; on the other hand, the constant regions of the two proteins appear to be identical. Comparison of the sequence of the heavy chain of He with the heavy chain sequences determined in other laboratories suggests that the variable region of subgroup II is at least 118 residues long. The nature and distribution of amino acid variations in this heavy chain subgroup resemble those observed in light chain subgroups. These studies provide evidence that the translocation hypothesis applies to heavy as well as to light chains, viz., genes for variable regions (V) are somatically translocated to genes for constant regions (C) to form complete VC structural genes.

Amino Acid Sequence↗
PubMedDate not supplied

Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition.

Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition. To determine if muscle atrophy could be minimized with exercise therapy, 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive: (1) no therapy (controls), (2) physical therapy thrice weekly (PT3), or (3) physical therapy five times weekly (PT5). Patients were studied through 35 days posttransplant. Muscle protein status and turnover was assessed by weekly nitrogen balance, and creatinine and 3-methylhistidine excretion. Results favored a muscle protein-sparing effect of exercise, as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity. Changes in arm muscle area correlated with energy, but not protein intake. Large individual variation, inadequate nutritional support and differences in admission arm muscle area may have clouded these results.

Acute Disease↗
PubMedDate not supplied

Intravenous branched chain amino acid trial in marrow transplant recipients.

Branched chain amino acids (BCAA) improve nitrogen balance and end-organ function in surgical patients, but are untested in marrow transplant recipients. We compared nitrogen balance, urinary 3-methylhistidine-to-creatinine ratio, upper arm anthropometry, serum prealbumin, and day to peripheral engraftment in a randomized, double-blinded trial between 45% (high-leucine) and 23% BCAA intravenous solutions in 40 adult leukemia patients for 1 month following allogeneic marrow transplantation. Nutritional support, provided at approximately 30 nonprotein calories/kg and 0.21 g nitrogen/kg ideal weight, did not differ between groups. Despite greater nitrogen loss and muscle breakdown evidenced by increased 3-methylhistidine-to-creatinine ratio and loss of arm muscle area by study end in the 45% BCAA, no statistical differences were observed when nitrogen balance was compared by week and within stress level as defined by organ and infectious complications. It is likely the patients in the 45% BCAA experienced greater metabolic stress by study end. Serum prealbumin and day posttransplant to peripheral engraftment also did not differ between groups. The chances (power) of this study exceeded 85% in detecting a difference in nitrogen balance of 2.5 g during study week 1 and 4.0 g during week 2. The power during week 3 was 77% for detecting a difference of 4.0 g, and it is unlikely that the true difference exceeds this magnitude. Thus, we did not find any evidence that intravenous BCAA-enriched solutions improved nitrogen balance during the first month after marrow transplantation.

Adolescent↗