Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4-35-7), which recognized HLA-A1, A23 and A24, were determined by means of the reverse transcriptase-polymerase chain reaction. This antibody was generated by Epstein-Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids, while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti-HLA antibody.
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PMID:Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA-A1, A23, and A24. 769 91

Cardiomyopathy due to monoclonal light chain deposits is a complication of plasma cell disorders. The deposits may be either fibrillar as in light chain amyloid or nonfibrillar as in light chain deposition disease. The reasons for these structural differences are still unknown. We characterized the myocardial deposits by immunohistochemical examination of sections and extraction and biochemical analysis of the tissue deposits in a patient (MCM) who died of myeloma and systemic light chain deposition disease. Amino acid sequence analysis of the extracted nonfibrillar MCM kappa-light chain reveals that it belongs to the L12a germline subset of the kappa(I) protein and contains five distinctive amino acid substitutions (three in the framework region III and two in the complementarity-determining region III) that have not been reported previously in the same positions in other kappa(I) light chains. The theoretically determined isoelectric point (pI 8.21) of the MCM light chain is high compared with the low isoelectric point of other Bence Jones proteins from subjects without light chain deposition disease. The diffuse binding to basement membranes and the high isoelectric point of the MCM kappa-light chain suggest electrostatic interaction as a possible mechanism of tissue deposition. The spatial locations of the five distinctive residues and a sixth rare substitution of the MCM protein modeled on the backbone structure of REI, a kappa(I)-soluble Bence Jones light chain of known three-dimensional structure, may be responsible for protein destabilization, partial unfolding, and aggregation leading to tissue deposition.
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PMID:Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. 862 4