Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine deaminase (EC 3.5.4.4. - ADA) deaminates adenosine and deoxyadenosine to inosine and deoxyinosine. The distribution of ADA isoenzymes depends on a binding protein. Purine nucleoside phosphorylase (EC 2.4.2.1. - PNP) catabolizes inosine and guanosine to hypoxanthine and guanine. Patients with severe combined immuno-insufficiency often suffer from a congenital ADA deficiency. The PNP deficiency is associated with severely defective T-cell immunity and normal B-cell immunity. Deficiency of ADA leads to an accumulation of adenosine, deoxyadenosine, adenine nucleotides (cAMP, dATP). In PNP deficiency an increased production of inosine, guanosine, deoxyinosine and deoxyguanosine was found. The pathogenesis of the immuno-insufficiency is to be traced back to disturbances in the purine metabolism interfering with the mitogenically induced lymphocyte transformation and other lymphocyte functions, as determined by in vitro tests. Deoxyadenine inhibits the ribonucleoside diphosphate reductase and synthesis of DNA. The overproduction of S-adenosyl-L-homocysteine inhibits methyltransferase reactions and 2'-deoxyadenosine the S-adenosylhomocysteine hydrolase. A decrease of ADA activities was found in T-lymphocytes of patients with Hodgkin's disease. Measurements of ADA activity in patients with leukemias do not explain the impairment of the cellular immune response in leukemias and may be regarded as indicator of increased purine metabolism. The ADA activities are increased in patients with acute immature and chronic myeloic leukemias depending on the activity of the disease. The ADA activity is low in chronic lymphatic leukemia. ADA inhibitors were used for the treatment of T-cell leukemias.
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PMID:[Immune insufficiency in enzyme defects of purine metabolism]. 630 5

Two new techniques were used to quantify cell death (i.e. DNA fragmentation) in situ: (1) 3' overhangs of the fragmented DNA were end labelled with biotin-7-dATP and TdT (peroxidase/DAB). (2) In situ nick translation (ISNT) was performed with DNA polymerase 1 and biotin-7-dATP, to label single strand segments of DNA (peroxidase/DAB). Both methods were tested to be negative in ischemic and tumor necrosis, and negative for mitotic figures. In 26 centroblastic Non Hodgkin lymphomas (CB) (monomorphous subtype [n = 9], polymorphous subtype [n = 7], secondary [n = 10]), 14 chronic lymphocytic leukemias and two immunocytomas these methods were employed to quantify the rate of cell death. ISNT proved to be more sensitive than end labelling. By ISNT, CB had a mean cell death rate of 250/10HPF (monomorphous type: 429/10HPF, polymorphous type: 222/10HPF, secondary: 111/10HPF). CLL showed a significantly lower rate (28/10HPF). These data suggest, that the low rate of cell turnover in CLL is indicated by a low rate of cell proliferation and a low rate of programmed cell death. In CB the high proliferation rate was accompanied by a high level of cell death. In CB/monomorphous a high turnover state with a very high proliferation and cell death rate was found, whereas CB/polymorphous represents an expansive state as indicated by a lower rate of cell death. CB/secondary showed almost no programmed cell death and therefore was interpreted as a high expansive state neoplasia.
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PMID:[Specific in situ labeling of apoptosis shows different rates of programmed cell death in non-Hodgkin lymphomas]. 788 32

The malignant Hodgkin and Reed-Sternberg cells of Hodgkin's lymphoma (HL) and HL-derived B cell lines were previously shown to be resistant to different apoptotic stimuli. We show here that cytochrome c fails to stimulate caspases-9 and -3 activation in cytosolic extracts of HL-derived B cells, which is due to high level expression of X-linked inhibitor of apoptosis (XIAP). Coimmunoprecipitation studies revealed that XIAP, apoptosis protease-activating factor-1, and caspase-3 are complexed in HL-derived B cell lysates. Even after stimulation with exogenous cytochrome c and dATP, XIAP impairs the proteolytic processing and activation of caspase-3. In cytosolic extracts, inhibition of XIAP by the second mitochondria-derived activator of caspases (Smac)/DIABLO, or immunodepletion of XIAP restores cytochrome c-triggered processing and activation of caspase-3. Smac or a Smac-derived agonistic peptide also sensitized intact HL-derived B cells for the apoptotic action of staurosporine. Finally, Hodgkin and Reed-Sternberg cells of primary tumor HL tissues also constitutively and abundantly express XIAP. The results of this paper suggest that high level XIAP expression is a hallmark of HL, which may play a crucial role in resistance to apoptosis.
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PMID:XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cells. 1287 65