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)

Collagen synthesis stimulated by materials released from platelets (MRFP) of patients with chronic granulocytic leukemia (CGL) and polycythemia vera (PV) was measured in human bone marrow fibroblasts derived from normal individuals. The MRFP of patients with CGL and PV stimulated normal fibroblast collagen synthesis significantly compared to the response from normal MRFP. Platelets derived from patients with CGL and PV may have some factors that dramatically stimulate collagen synthesis which is relevant to the frequently observed myelofibrosis in these diseases.
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PMID:Increased collagen synthesis of bone marrow fibroblasts by materials released from platelets of chronic granulocytic leukemia and polycythemia vera. 308 91

In 9 patients with myeloproliferative diseases (MPD) (6 with myelofibrosis, MF, 1 with Ph1 positive chronic granulocytic leukaemia, CGL, 1 with primary eosinophilia, PE, 1 with pre-leukaemia syndrome, preL) collagen, epinephrine, and ADP-induced aggregation, N-ethylmaleimide-induced malondialdehyde (MDA) production, beta-thromboglobulin (beta-TG) plasma levels, and platelet turnover were studied. Collagen-induced aggregation was found to be normal in 7 patients, absent in 1, and reduced in 1. In all but 3 patients, aggregation with ADP was markedly reduced. Epinephrine-induced aggregation was decreased in 7 patients. No difference was found between mean MDA production in MPD (3.21 +/- 0.50 nmol/10(9) PLTs) and in control group of 21 normal subjects (3.04 +/- 0.26 nmol/10(9) PLTs). Mean beta-TG levels were significantly higher (P less than 0.01) in MPD patients (165.00 +/- 28.29 ng/ml) than in healthy controls (81.76 +/- 14.63 ng/ml). Mean platelet production half-time was significantly shorter in MPD (2.48 +/- 0.24 d) than in the control group (3.43 +/- 0.17 d), after adjustment for age by covariance analysis (P less than 0.005). Our data do not indicate an abnormal prostaglandin synthesis and are consistent with the hypothesis that a disseminated intravascular platelet aggregation might take place in MPD patients.
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PMID:Defective platelet aggregation and increased platelet turnover in patients with myelofibrosis and other myeloproliferative diseases. 646 Oct 58

To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins.
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PMID:Accumulation of Maillard reaction products in skin collagen in diabetes and aging. 851 58

We conducted a retrospective study to assess the changes in bone marrow (BM) stromal antigenic profile and fibrosis in chronic myeloid leukemia (CML) under combined interferon-alpha (IFN) and Ara-c therapy. Bone marrow biopsies were taken before therapy and twice (at 4 and 15 months) during therapy in 10 CML patients and compared with non-CML samples. Collagen and reticulin fibrosis was assessed by histochemical methods and phenotypic changes were studied by immunohistochemistry (APAAP) with antibodies directed against endothelial cell antigens, cell adhesion molecules, and HLA-DR. It was found that: (1) BM endothelial cells in patient and in control specimens showed a specific pattern of antigen expression: high expression of FVIII and CD34 (except on sinusoids for the latter), variable expression of UEA I, and no expression of HLA-DR and E-selectin. (2) Compared to non-CML controls, CML specimens at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopoietic cells. (3) Treatment did not influence BM fibrosis, the vascular content of the BM, or the expression of the antigens tested except an increase in the number of CD34+ sinusoids (5/10 patients), an increase in the number of HLA-DR+, and a decrease in the number of CD34+ hemopoietic cells (6/10). (4) On therapy, difficulty in aspiration and/or reduced BM fragment numbers were noted in 8 of 10 patients whose bone marrow was still normocellular or slightly hypercellular. In conclusion, CML samples at diagnosis showed increased fibrosis and decreased CD31 and CD61 expression compared to controls. During the period of observation, combined therapy did not modify BM fibrosis; however, an increase in CD34+ sinusoids and a decrease in CD34+ hemopoietic cells were noted.
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PMID:Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. 904 64

Diabetes increases the risk of bone fracture. Organic and inorganic bone extracellular matrix components determine bone strength. Previous studies indicate that in diabetes, glycation of collagen causes abnormal arrangements of collagen molecules and fragile bones. Diabetic bone fragility is additionally attributed to reduced levels of lysyl oxidase enzyme-dependent collagen cross-links. The mechanism underlying the presence of lower enzymatic collagen cross-links in diabetic bone has not been directly investigated. Here we determine in primary osteoblast cultures the regulation of lysyl oxidase protein by type I collagen and collagen modified by carboxymethylation (CML-collagen), a form of advanced glycation endproducts. Data indicate that non-glycated collagen up-regulates lysyl oxidase levels both in primary non-differentiated and in differentiating mouse and rat osteoblast cultures, while CML-collagen fails to regulate lysyl oxidase in these cells. Collagen binding to Discoidin Domain Receptor-2 (DDR2) mediates lysyl oxidase increases, determined in DDR2 shRNA knockdown studies. DDR2 binding and activation were disrupted by collagen glycation, pointing to a mechanism for the diminished levels of lysyl oxidase and consequently low lysyl oxidase-derived cross-links in diabetic bone. Our studies indicate that collagen-integrin interactions may not play a major role in up-regulating lysyl oxidase. Furthermore, non-collagenous ligands for the receptor for advanced glycation end products (RAGE) failed to alter lysyl oxidase levels. Taken together with published studies a new understanding emerges in which diabetes- and age-dependent inhibition of normal collagen-stimulated DDR2- and integrin-signaling, and independent advanced glycation-stimulated RAGE-signaling, each contributes to different aspects of diabetic osteopenia.
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PMID:Collagen advanced glycation inhibits its Discoidin Domain Receptor 2 (DDR2)-mediated induction of lysyl oxidase in osteoblasts. 2412 Mar 83