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[Activity of pyrimidine 5'nucleotidase (py5'Nd) of erythrocytes in essential hypertension].

Activity of pyrimidine 5'nucleotidase was measured in hemolysate of erythrocytes of healthy persons and patients with essential hypertension. Cytidine 5'monophosphate (CMP) and uridine 5'monophosphate (UMP) were used as the substrates for evaluation of activity of so called I-isoenzyme and uridine 3'monophosphate (U3'MP) was used as a substrate for the II isoenzyme of Py5'Nd. It was found that the activity of Py5'Nd I was lower in hypertensives (26.8 mU/gHb (CMP)) and 69.3 mU/gHb (UMP) in comparison with normotensives (62.3 and 117.4 mU/gHb respectively) (p < 0.05). The activity of Py5'Nd II did not differ between studied groups. Possible metabolic consequences of decreased activity of Py5'Nd are discussed.

5'-Nucleotidase↗

[Adenylate cyclase and 5'-nucleotidase activities in the sensorimotor and limbic structures of the rat brain after training in a manipulative skill].

The activities of adenylate cyclase (AC) and 5'-nucleotidase (NT) were studied in the limbic (amygdala, hippocampus) and sensorimotor (cortex, striatum) brain structures of three rat groups: control (without training), not well and well learning to perform movements with pushing the operandum. It was found, that after training the activity of AC was decreased in all structures studied. Moreover, in the cortex and the striatum the decrease was more pronounced in the group of well learning rats, while in the amygdala--in not well learning ones. The activity of NT in all brain structures, excepting the striatum, was more significantly decreased in the rats with low ability to learn the movements with prolonged pushing. Only in the striatum the increase of NT activity (initially the lowest in the control animals--1.0 +/- 0.04 microgram P(i)/mg protein/min) up to 1.3 +/- 0.1 in not well and up to 2.0 +/- 0.1 in well learning animals was found. The interhemispheric [correction of intrahemispheric] asymmetry of AC activity in the cortex and of NT in the hippocampus was revealed. Thus, the changes of the activity of the enzymes, participating in the biogenesis of adenosine (NT) and c-AMP (AC) are different in the limbic and sensorimotor structures dependently on learning ability of rats. The increase of NT activity after learning only in the striatum could reflect a specific role of purinergic system of this brain structure in the regulation of sensory controlled movements.

5'-Nucleotidase↗

[Variation of cholostase enzymes (5'-nucleotidase and alkaline phosphatase) during a specific treatment for malaria in the Gabonese child].

Biological variations of 5'nucleotidase (5'NU) and alkaline phosphatase (AP) in 102 Gabonese children with malaria features (MF) and malaria infection (MI) receiving treatment are reported. [formula: see text] During the therapeutic assay, 5'NU rate decreases faster than AP'S; Fourteen days after the beginning of treatment, difference between AP MF and AP M1 is still significant. Enzymes decrease is an indication of the malaria drugs tolerance (MSP (*)).

5'-Nucleotidase↗

[Method of comparative evaluation of cytotoxicity of low-soluble dust by lowered activity of 5-nucleotidase in macrophage culture].

The authors suggest a new method to evaluate cytotoxicity of silicosis-dangerous dust through lowered activity of 5'-nucleotidase, a marker of cytolemma, in macrophageal culture. The scientists used the new method to compare cytotoxicity of 4 groups of industrial dust and correlated the results with those obtained in the test of lowered viability of macrophages (by incorporation of trypan blue). Both tests appeared to have correlation of the dust ranks according to cytotoxicity grade. Damage and activation of macrophages by products of their destruction change the cytotoxicity grade in the same direction, so the results could be considered more easily than for the tests where the changes are in opposite directions.

5'-Nucleotidase↗

A de-sialylated isoform of serum 5'-nucleotidase: clinical and biological significance in hepatobiliary disease.

Using an electrophoretic technique on cellulose acetate, three multiple forms of the 5'-nucleotidase (5'NU) with mobilities alpha 1, alpha 2, and beta appear in the serum of healthy subjects. The difference between the alpha 1 and alpha 2 isoforms lies in their sialylation degree, the alpha 2-5'NU being a de-sialylated form. In 147 patients with different hepatobiliary diseases the alpha 2 isoform was present in only 19% of cases, and there was no significant difference in the activity of total 5'NU, alpha 1-5'NU and beta-5'NU between patients with or without alpha 2-5'NU, alpha 1-5'NU and beta-5'NU (P < 0.001), as with other biochemical indicators of liver damage. It is suggested that in hepatobiliary diseases an increase of the sialylation of serum 5'NU occurs, which would explain the absence of the desialylated alpha 2 isoform in the majority of cases. However, the decrease of hepatic receptors of asialoglycoproteins would lead to an increase of this de-sialylated isoform in the serum of certain patients.

5'-Nucleotidase↗

Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine.

The agent 2-chlorodeoxyadenosine (2-CdA) has chemotherapeutic activity in hairy cell leukemia (HCL) and in refractory chronic lymphocytic leukemia (CLL). The cytotoxic activity of 2-CdA requires the intracellular accumulation of 2-CdA nucleotides. Deoxycytidine kinase (dCK) and cytoplasmic 5'-nucleotidase (5'-NT) are the principal enzymes that phosphorylate 2-CdA and dephosphorylate 2-CdA 5'-monophosphate, respectively. The net accumulation of 2-CdA nucleotides may therefore depend on both dCK and 5'-NT. The purpose of the present experiments was to determine if there is a relationship between pretreatment levels of dCK and 5'-NT in HCL and in CLL cells, and the clinical outcome of 2-CdA treatment. As measured by a direct immunoassay for dCK in 25 CLL patients, and by a 5'-NT activity assay in 23 patients, mean dCK levels were significantly higher in 2-CdA responders than in nonresponders (P < .01), whereas mean 5'-NT levels were significantly lower in 2-CdA responders than in nonresponders (P < .05). Mean dCK levels were higher in six HCL 2-CdA responders than in one nonresponder, whereas mean 5'-NT levels were lower in the 2-CdA responders than in the nonresponder. These results suggest that both dCK and 5'-NT are determinants of 2-CdA responsiveness.

5'-Nucleotidase↗

5' nucleotidase activity in leukaemic lymphocytes.

The enzyme 5' nucleotidase (E.C.3.1.3.5.) is present in lymphocytes isolated from the blood of normal subjects. The activity was extremely low in lymphocytes from 17 patients with B lymphocytic leukaemias. Removal of normal lymphocytes from the B-cell leukaemic samples decreased further the enzyme activity. Moderately low values were observed in three cases of T-ALL and in the cells from a case of Sézary syndrome. In contrast, normal or high values were observed in three cases of ALL in which T and B markers were not demonstrable and in two of T-CLL. No differences were observed in partially purified subpopulations of normal B and T cells.

B-Lymphocytes↗

[A method for the primary selection of immunomodulators by the level of 5'-nucleotidase activity in the macrophages of peritoneal exudate].

A method of primary selection of immunomodulators based on measuring of ecto 5'-nucleotidase activity level of macrophages of peritoneal exudate was developed. Immunostimulators were found to decrease the activity level, while immunosuppressors increased the activity. The preparations having no immunomodulatory effect do not change the activity of this enzyme.

5'-Nucleotidase↗

[Alkaline phosphatases in human feces, intestinal mucosa and bile, and the occurrence of 5'-nucleotidase in feces (author's transl)].

Alkaline phosphatase (EC 3.1.3.1) in extracts of human feces resembles alkaline phosphatase in extracts of duodenal mucosa, except for its electrophoretic mobility in starch gel. It is very probable that the normal feces alkaline phosphatase derives from intestinal mucosa. Gall bladder alkaline phosphatase, which is markedly different, has not been found in normal feces. Some patients with acute viral hepatitis or protozoasis excrete an alkaline phosphatase which resembles gall bladder alkaline phosphatase and has the characteristics of 5'-nucleotidase (EC 3.1.3.5). The appearance of this enzyme correlates with low total alkaline phosphatase activity of the excreta.

Adult↗

5'-Nucleotidase and adenosine deaminase activities in hypertrophied rat heart. The effect of tachycardia.

Activity of 5'-nucleotidase (5NT) and adenosine deaminase (ADA) in the left heart ventricle was examined at normal heart rate and after atrial pacing in six weeks after constriction of the aorta above or below the renal vessels and in sham operated rats. The aorta constriction above the vessels reduced activity of 5NT by 29% and increased activity of ADA by 33%, whereas the constriction below the vessels resulted in elevated activity of both enzymes: 5NT by 16% and ADA by 145% at normal heart rate. The atrial pacing reduced 5NT activity and did not affect ADA activity in control rats and in those with constriction of the aorta below the vessels. The activity of both enzymes increased after constriction of the aorta above the renal vessels. It is concluded that adenosine metabolism in the hypertrophied heart may be changed due to changes in its production and degradation. Renin-angiotensin-aldosterone system seems to be involved in regulation of the activities of adenosine metabolizing enzymes in the hypertrophied heart.

5'-Nucleotidase↗

Cytochemical demonstration of nitric oxide synthase and 5' nucleotidase in human glioblastoma.

Both nitric oxide (NO), formed from L-arginine by the enzyme nitric oxide synthase (NOS), and adenosine, which is produced by 5' nucleotidase (5' N) acting on adenosine 5' monophosphate (5' AMP) are implicated in several neurophysiological processes. In addition, 5' N is a linker protein involved in cell motility. Alterations of both enzyme activities seem to be responsible for some pathological states of the central nervous system (CNS). In the present report, we have studied the cytochemical demonstration of NOS and 5' N activities in human glioblastoma cells. Enzyme activity of both was observed in tumor cells; moreover, the coincidence of enzyme histochemistry and immunohistochemistry for NOS was noted in most cases. The findings were interpreted on the basis of the cytotoxic effects due to NO production by tumor cells, and on the non-catalytic role of membrane 5' N which acting as an adhesive molecule can favour tumor invasiveness.

5'-Nucleotidase↗

Simple, direct determination of serum 5'-nucleotidase.

A simple determination of 5'-Nucleotidase in blood serum without deproteinization is described. The enzyme activity is distinguished from that of a nonspecific alkaline phosphatase by nickel inhibition and the inorganic phosphate released from adenosine monophosphate used as substrate is determined by a method previously described. Additional studies include the determination of optimal conditions for the reaction and nickel inhibition.

Alkaline Phosphatase↗

Lack of cross-resistance with gemcitabine and cytarabine in cladribine-resistant HL60 cells with elevated 5'-nucleotidase activity.

Cross-resistance patterns between chemotherapeutic agents have implications for the treatment of hematologic and other diseases. Previous in vitro models have shown cross-resistance between the purine analog 2-chlorodeoxyadenosine (cladribine) and the pyrimidine analogs 2',2'-difluorodeoxycytidine (gemcitabine) and 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside, cytarabine) with reduced deoxycytidine kinase (dCK) activity as the underlying determinant of resistance. In this study, we continuously exposed the human promyelocytic leukemia cell line HL60 to as much as 1024 nM cladribine. After limiting dilution, the cladribine concentrations that caused 50% growth inhibition (IC50) of the two clones R13 and R23 were 33.3- and 18.7-fold, respectively, higher than the IC50 of the parental HL60 cells (8.7+/-1.3 nM). These cladribine-resistant clones, however, showed no cross-resistance to gemcitabine and only 3.3- and 2.7-fold resistance to cytarabine, respectively. Characterization of both clones revealed stably elevated levels of purine-specific "high-Michaelis constant (Km)" 5'-nucleotidase (5'-NT) messenger RNA expression and specific activity, whereas pyrimidine-specific "low-Km" 5'-NT activity was undetectable, and dCK activity was only marginally decreased in R13. Thus, the ratio of dCK (specific for cladribine) to high-Km 5'-NT activity in R13 and R23 was reduced to 65.3% and 63.7%, respectively. These results show that changes of high-Km 5'-NT activity can induce cladribine resistance, without cross-resistance to gemcitabine.

5'-Nucleotidase↗