Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dialysis-related amyloidosis (DRA) is a serious complication in long-term dialysis patients, and presents with carpal tunnel syndrome, cystic bone lesions, destructive spondylarthropathy, diffuse arthritis and periarthritis, systemic organ involvement, and dialysis-related spinal canal stenosis (DSCS). Recently a new concept of DSCS has been proposed that includes both destructive spondylarthropathy and myeloradiculopathy induced by extradural thickness. beta(2)-microglobulin (beta(2)M) amyloid was demonstrated to be modified with advanced glycation end products (AGEs) such as imidazolone, N(epsilon)-(carboxymethyl)lysine (CML), and pentosidine. Imidazolone is a reaction product of arginine residue in proteins with 3-deoxyglucosone (3-DG), which is markedly accumulated in uremic serum. Imidazolone is generated under nonoxidative conditions, while CML and pentosidine are formed by oxidative processes. Immunoelectron microscopy demonstrated that AGEs were localized not only in dialysis amyloid but also in nonamyloid collagenous structures, supporting the hypothesis that AGE modification of collagen might have pathogenic relevance in the deposition of beta(2)M on collagen. Serum levels of AGEs are increased in uremic patients. The dimeric form of beta(2)M in the dialysate and urine of uremic patients is more susceptible to imidazolone modification as observed in dialysis amyloid. However, the major component of dialysis amyloid is a native form of beta(2)M, while AGE-modified beta(2)M and truncated beta(2)M are the minor components. Thus I propose that 3-DG and the other dicarbonyl compounds accumulating in uremic serum promote the modification of beta(2)M with AGEs mainly after deposition of beta(2)M as amyloid. For the prevention and treatment of DRA, beta(2)M should be efficiently eliminated from circulating blood by kidney transplantation, hemodialysis, or hemodiafiltration using high-flux membranes and an adsorbent (Lixelle) column.
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PMID:Dialysis-related amyloidosis: pathogenesis focusing on AGE modification. 1126 80

A median motor nerve latency (DML) is generally prolonged in the carpal tunnel syndrome (CTS) of hemodialysis patients. Meanwhile, the advanced glycation process of proteins has been reported to be involved in the pathogenesis of the dialysis related amyloidosis. To investigate the role of carboxymethylation in dialysis related CTS, we measured a circulating carboxymethyllysine-hemoglobin (CML-Hb) level and nerve conduction velocity in 44 hemodialysis patients. The circulating CML-Hb level was 6.56 +/- 3.18 nmol CML/mg Hb, median motor nerve conduction velocity (NCV) was 49.8 +/- 4.64 m/s, median DML was 4.44 +/- 1.06 ms, and difference between median DML and ulnar DML (Delta DML) was 1.68 +/- 1.09 ms. Median and ulnar nerve NCV showed no correlation with circulating CML-Hb level. Both median DML and Delta DML were significantly correlated with CML-Hb (r = 0.429, P = 0.003, r = 0.472, P = 0.001). This study provided additional clinical evidence of an involvement of an advanced glycation process in the pathogenesis in CTS in hemodialysis patients.
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PMID:A possible involvement of the carboxymethylation process in carpal tunnel syndrome in hemodialysis patients. 1515 81