Disease relevance of NP

• A decrease in the percentage of PNP-positive cells concomitant with a relative increase of cells with the low enzyme activity was observed in the lymphocytes of nine patients with chronic lymphocytic leukemia (CLL) [1].
• The PNP and ADA staining was observed in lymphoid cells of patients with lymphoproliferative disorders [1].
• Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis [2].
• Cells from 13 patients with T acute lymphoblastic leukemia (ALL) and 10 patients with T lymphoblastic lymphoma (LL) had very high levels of ADA (respectively 13.0 +/- 5.4 and 22.8 +/- 14) and low levels of PNP (respectively 1.9 +/- 0.8 and 2.5 +/- 1.4) [3].
• These results show that specific stages of T-cell development may be characterized by the relationships and the correlation between the two enzymes and suggest that T-ALL and T-LL appear to be the group of lymphoid malignancies with a high degree of incoordination between ADA and PNP activities [3].

Psychiatry related information on NP

• Detection of respiratory-related arousals was also improved by NP and only 3% could account for mouth breathing respiration [4].
• Optimum conditions for enzymatic hydrolysis of OCE were 50 degrees C, 2 h of reaction time, 0.1% amylase mixture (alpha-amylase plus glucoamylase), and 0.2% protease NP [5].

High impact information on NP

• However, GMP-PNP vesicles fail to target and fuse with the Golgi complex whereas GTP vesicles are functional [6].
• Uncapped U- or G-initiated transcripts were obtained in the presence of UMP-PNP or GMP-PNP, the respective imidodiphosphate analogs [7].
• Purine nucleoside phosphorylase deficiency: improved metabolic and immunologic function with erythrocyte transfusions [8].
• Deoxyguanosine toxicity on lymphoid cells as a cause for immunosuppression in purine nucleoside phosphorylase deficiency [9].
• Characterization of a cell culture model for the study of adenosine deaminase- and purine nucleoside phosphorylase-deficient immunologic disease [10].

Chemical compound and disease context of NP

• Purine nucleoside phosphorylase (PNP), the enzyme schematically next to adenosine deaminase in the purine salvage pathway, has been demonstrated cytochemically in peripheral blood lymphocytes of healthy subjects and chronic lymphocytic leukemia (CLL) patients [11].
• Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency [12].
• Combined assay of adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in the early clinical evaluation of B-chronic lymphocytic leukemia [13].
• Thus, we have determined if there is a differential distribution of adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzyme fluxes in glia, comparing primary cultures of central and ciliary ganglion neurons and glial cells from chick embryos [14].
• The erythrocyte adenosine deaminase, nucleoside phosphorylase, hypoxanthineguanine phosphoribosyltransferase and adenine phosphoribosyltransferase activities and plasma urate concentrations were measured in 20 cases of Down's syndrome and in 20 age- and sex-matched control subjects [15].

Biological context of NP

• The NP activities of the father, mother and brother of the propositus are in the heterozygote range [16].
• We performed a study in 83 children with untreated ALL to establish the relationships of ADA and PNP to clinical outcome, in vitro drug resistance and differentiation stage of B-cell lineage ALL [2].
• In the PNP-deficient patient, chimerism has not been documented on enzymatic testing [17].
• However, there is controversy about the identity of the nucleoside kinases that are responsible for intracellular phosphorylation of deoxyadenosine in adenosine deaminase deficiency and deoxyguanosine in purine nucleoside phosphorylase deficiency [18].
• Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals [19].

Anatomical context of NP

• 2. In the propositus no purine nucleoside phosphorylase (NP) activity could be detected in her red cells and lymphocytes, while the ADA activity was somewhat increased [16].
• In the two patients with PNP deficiency, contrary to the classical descriptions of this disorder, T-cell function fluctuated with time [17].
• Three of the ADA-deficient patients and one of the PNP-deficient patients were given transplants of haploidentical parental bone marrow stem cells without pretransplant immunosuppression [17].
• Erythrocyte adenosine deaminase and purine nucleoside phosphorylase activity in gout [20].
• The demonstration of substantial human PNP or ADA activity in virus-infected mouse fibroblasts by isozyme analysis suggested that active gene product was translated from either spliced or bicistronic message [21].

Associations of NP with chemical compounds

• The decreased activity of NP was not only found for the substrate inosine but also when guanosine or xanthosine were used as substrate [16].
• Deoxyadenosine and deoxyguanosine, substrates that accumulate in ADA and deoxyguanosine, substrates that accumulate in ADA and PNP deficiency, respectively, appear to be selectively phosphorylated by lymphoid cells to the corresponding deoxynucleoside triphosphate, resulting in inhibition of DNA synthesis in these cells [22].
• Because the immune deficiency in AIDS is similar to that in some purine enzyme deficiencies, we measured erythrocyte adenosine deaminase (ADA) and purine nucleoside phosphorylase activities in patients with AIDS, heterosexual controls, and a high-risk asymptomatic population [23].
• These viruses also contained a human hypoxanthine phosphoribosyltransferase gene as a selectable marker and a mouse metallothionein promoter (MMP) sequence just upstream from the PNP or ADA genes [21].
• No other enzyme deficient line formed any dGTP--with or without the PNP inhibitor 8-aminoguanosine (8-NH2GR)--with one exception [24].

Regulatory relationships of NP

• We found that a hemolysate from a patient with purine nucleoside phosphorylase deficiency had only 7% of control AdoHcyase activity, conforming the original observation [25].

Other interactions of NP

• A suspension of living lymphocytes is mixed with agarose sol containing the reagents for the detection of PNP or ADA activity on a glass slide [1].
• An inverse relationship between the two phosphorylases was demonstrated in patients, with higher MTA-phosphorylase and lower PNP activities than in control subjects [26].
• Adenosine deaminase, nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase activity in normal lymphocyte subpopulations [27].
• Endothelial cell activities were notably different from those in the human heart particularly in the case of SAHH (nine-fold higher) and PNP (16-fold higher).(ABSTRACT TRUNCATED AT 250 WORDS)[28]
• Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans [29].

Analytical, diagnostic and therapeutic context of NP

• 3. With starch gel electrophoresis no NP activity could be detected in the patient's haemolysate [16].
• No effects on ADA and PNP levels appeared to be induced by chemotherapy [30].
• Based on this information, ADA and NP activities were examined in a variety of congenital and acquired animal models of dysimmunity [31].
• The patient's PNP cDNA was amplified by PCR and sequenced [32].
• In order to prove that these mutations were responsible for the disease state, each of the three mutations was constructed separately by site-directed mutagenesis of the normal PNP cDNA, and each was transiently expressed in COS cells [32].

References