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)

Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.
Proc Eur Dial Transplant Assoc 1976
PMID:Transplant monitoring: patterns of the immune response. 77 32

The amount of advanced glycation end-products (AGE) in tissue proteins increases in diabetes mellitus, and the concentration of a subclass of AGEs, known as glycoxidation products, also increases with chronological age in proteins. The rate of accumulation of glycoxidation products is accelerated in diabetes and age-adjusted concentrations of two glycoxidation products, N epsilon-(carboxymethyl)lysine (CML) and pentosidine, correlate with the severity of complication in diabetic patients. Although AGEs and glycoxidation products are implicated in the development of diabetic complications, these compounds are present at only trace concentrations in tissue proteins and account for only a fraction of the chemical modifications in AGE proteins prepared in vitro. The future of the AGE hypothesis depends on the chemical characterization of a significant fraction of the total AGEs in tissue proteins, a quantitative assessment of their effects on protein structure and function, and an assessment of their role as mediators of biological responses. In this manuscript we describe recent work leading to characterization of new AGEs and glycoxidation products. These compounds include: (1) the imidazolone adduct formed by reaction of 3-deoxyglucosone with arginine residues in protein; (2) N epsilon-(carboxyethyl)lysine, an analogue of CML formed on reaction of methylglyoxal with lysine; (3) glyoxal-lysine dimer; and (4) methyl-glyoxal-lysine dimer, which are imidazolium crosslinks formed by reaction of glyoxal or methylglyoxal with lysine residues in protein. The presence of 3-deoxyglucosone, methylglyoxal and glyoxal in vivo and the formation of the above AGEs in model carbonyl-amine reaction systems suggests that these AGEs are also formed in vivo and contribute to tissue damage resulting from the Maillard reaction.
Nephrol Dial Transplant 1996
PMID:New biomarkers of Maillard reaction damage to proteins. 904 6

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.
Nephrol Dial Transplant 1996
PMID:Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions. 904 7

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.
Semin Dial
PMID:Dialysis-related amyloidosis: pathogenesis focusing on AGE modification. 1126 80

Molecular remissions were observed in some relapsed post allogeneic transplant chronic myeloid leukemia (CML) patients who received donor peripheral blood lymphocyte infusions (DLI). This was indirect evidence of immune-mediated tumor cell killing, and the process was termed graft-versus-leukemia (GVL). Mechanisms were hypothesized to be direct T cell mediated cell lysis or augmented programmed cell death. These observations formed the basis for exploring the role of DLI first in relapsed allogeneic transplant patients with other hematologic malignancies, then as prophylaxis for patients at high risk for relapse and then as adjunctive therapy for transplant strategies utilizing non-myeloablative conditioning regimens. Multiple clinical trials are underway to define dose, schedule, clinical and molecular response and laboratory assays to distinguish lymphocyte subsets mediating GVL and those responsible for graft-versus-host disease (GVHD) toxicity. This review outlines some of the donor/patient and therapy variables involved and some principles of mononuclear cell collection for cellular immunotherapy.
Ther Apher Dial 2003 Jun
PMID:A clinical role for peripheral blood lymphocyte infusions and perspectives on collection. 1292 5

Reduced-intensity hematopoietic stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than that of conventional HSCT. Favorable results have been reported particularly in hematological malignancies, such as chronic myelocytic leukemia and malignant lymphoma. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease and graft-versus-tumor remains unclear. More knowledge on the mechanism is crucial to enhance antitumor effect and to further improve the prognosis.
Ther Apher Dial 2003 Jun
PMID:Development of reduced-intensity hematopoietic stem cell transplantation in the National Cancer Center Hospital, Japan. 1292 7

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.
Ther Apher Dial 2004 Jun
PMID:A possible involvement of the carboxymethylation process in carpal tunnel syndrome in hemodialysis patients. 1515 81

Extreme thrombocytosis is a frequent feature in myeloproliferative disorders which can predispose a person to thrombotic complications. As opposed to other myeloproliferative disorders, symptomatic thrombocytosis is rare in chronic myeloid leukemia. We describe a second case report of chronic myeloid leukemia (Ph chromosome positive) in a patient in chronic phase on hydroxyurea who presented with sudden onset digital cyanosis of the left hand, giddiness, headache and malaise due to extreme thrombocytosis. A 67% global reduction in the platelet count from 1553 x 10(9)/L to 513 x 10(9)/L after two therapeutic plateletpheresis procedures was seen. There was simultaneous improvement in all symptoms except cyanosis on the tip of the middle finger that progressed to dry gangrene. Dramatic reduction in the platelet count and ablation of symptoms by therapeutic plateletpheresis is an effective therapy and should begin as soon as possible.
Ther Apher Dial 2004 Dec
PMID:Therapeutic plateletpheresis in a case of symptomatic thrombocytosis in chronic myeloid leukemia. 1566 50