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At least 19 recordsLinked to original sources
PubMed1975

Immunological observations on patients with Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation.

Three patients with the Lesch-Nyhan syndrome were found to have normal delayed hypersensitivity, peripheral-blood T-lymphocyte counts, lymphocyte responses to P.H.A., and serum IgM, IgA, and IgE levels. However, the percentages of B-lymphocytes, IgG levels, serum-isohaemagglutinin titres, and lymphocyte responses to pokeweed mitogen (P.W.M.) were subnormal. These observations suggest that activity of the salvage pathway of purine synthesis catalysed by hypoxanthine-guanine phosphoribosyl transferase (H.G.P.R.T.) is not required for the responses of T-lymphocytes to mitogenic or antigenic stimulation, but may contribute to the proliferation and function of B lymphocytes. The major role of the de-novo pathway of purine synthesis in human lymphocyte responses to mitogenic or antigenic stimulation is shown by the effects of inhibitors of this pathway, including immunosuppressive agents, and by the effects of congenital deficiency or inhibition of adenosine deaminase.

Adenosine Deaminase↗
PubMed1976

Phosphoribosylpyrophosphate synthetase is elevated in fibroblasts from patients with the Lesch-Nyhan syndrome.

In subconfluent cultures of fibroblasts from patients with complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase activity is elevated. The abnormally high catalytic activity of the synthetase appears to account for the overproduction of purines by the cultured mutant cells and presumably for that by the patients.

Cell Division↗
PubMed1977

Purine mutants of mammalian cell lines: III. Control of purine biosynthesis in adenine phosphoribosyl transferase mutants of CHO cells.

Spontaneous and mutagen-induced 2,6-diaminopurine-resistant mutants of Chinese hamster ovary (CHO-K1) cells were isolated. Such mutants fell into two classes: spontaneous and ethylmethane-sulfonate-induced mutants had approximately 5% wild-type adenine phosphoribosyl transferase (APRT) activity, whereas ICR-170G-induced mutants had barely detectable APRT activity. Since it has been reported that human hypoxanthine-guanine phosphoribosyl transferase (HGPRT) (Lesch-Nyhan syndrome) and APRT mutants over-produce purines, we examined the control and rate of purine biosynthesis in the Chinese hamster mutants. End product inhibition by adenine could not be demonstrated in such mutants, indicating that the active feedback inhibitor is a nucleotide rather than the free purine base, HGPRT activity was normal in all mutants examined except in one isolate. Purine biosynthesis as measured by the accumulation of the purine biosynthetic intermediate phosphoribosyl formylglycineamide was not elevated in the mutants as might have been predicted from work with Lesch-Nyhan cells. The data also suggest that our strain of CHO-K1 is physically or functionally haploid for the APRT locus.

Adenine Phosphoribosyltransferase↗
PubMed1978

[Immunodeficiencies and enzyme deficiencies].

The first part of the paper outlines the actual situation of the recent investigations on the interpretative problem of the immunological deficits combined with enzymatic deficits. ADA deficit associated with combined immunodeficiency is an autosomal recessive form. Low enzyme levels, which is produced by a structural gene located on chromosome 20, were detected in chronic lymphatic leukemias where ADA decrease is correlated to low levels of T lymphocytes and the prevalence of an atypical B lymphocyte population. Particularly high levels of ADA were detected in acute lymphoblastic leukemias, in transplant rejection, in blastic crisis of chronic myeloid leukemia... NP deficit is associated with a T branch immunodeficiency, with high levels of inosine, guanosine, hypouricemia, hypochromic microcythemia and hematopoietic tissue megaloblastosis. This enzyme, with trimeric structure, whose structural gene is located on chromosome 14, shows a cytoplasmic location, and its maximum activity is to be found in T lymphocytes separated by rosetting. IGPT deficit is to be held responsible for the neurological Lesch-Nyhan syndrome. This deficit is associated with a depression of B lymphocyte function evaluated as response to the mitogens (PWM, Protein A) or as specific immunoglobulins production. At last the Authors report some personal investigations performed on hemolysates and lymphocytes of subjects with impaired immunity, as well as on some children at birth to establish the correlation between ADA and NP behaviour and immunosurveillance. Lastly, the data on the variations of the enzymatic and immunological parameters of subjects with immunodeficiency associated to enzymopenia after red cell transfusion are reported.

Adenosine Deaminase↗
PubMed1975

Phosphoribosylpyrophosphate overproduction, a new metabolic abnormality in the Lesch Nyhan syndrome.

The activity of phosphoribosylpyrophosphate synthetase and the rate of phosphoribosylpyrophosphate accumulation are significantly increased in cultured lymphocytes of Lesch Nyhan patients deficient in hypoxanthine guanine phosphoribosyltransferase and in a clone of mutagen-induced, hypoxanthine guanine phosphoribosyltransferase deficient human lymphocytes. The increase in phosphoribosylpyrophosphate synthetase activity is the cause of the abnormally high cellular phosphoribosylpyrophosphate content and possibly of the purine overproduction described in this syndrome.

Cell Line↗
PubMed1977

The purinergic nerve hypothesis.

Experiments over the past decade have revealed a third component in the autonomic nervous system which is neither adrenergic nor cholinergic. These nerves are strongly represented in the gastrointestinal tract of a wide range of vertebrate species and have also been identified in lung, trachea, retractor penis, bladder, oesophagus, eye, seminal vesicle and in some parts of the cardiovascular system and brain. Evidence has been presented that the principal active substance released by these nerves in the gut is a purine nucleotide, probably ATP, and they have therefore been termed 'purinergic'. The evidence includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) mimicry by exogenously applied ATP of the action of nerve-released transmitter; (4) the presence of Mg2+-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) the similar blocking and potentiating effects produced by drugs on the responses to exogenously applied ATP and nerve stimulation. A tentative model for the synthesis, storage, release and inactivation of ATP during purinergic nerve transmission is proposed. Some properties of purinergic receptors are described.

Adenine Nucleotides↗
PubMed1979

An ultramicrochemical test for mycoplasmal contamination of cultured cells.

A sensitive ultramicrochemical enzyme test for mycoplasmal contamination of cultured cells, based on the determination of the activity of adenosine phosphorylase, is described. The test was performed by assaying the enzymatic conversion of [8-14C]adenine and ribose-1-phosphate to [8-14C]adenosine by incubating a plastic leaflet carrying a counted number of cells (1 to 10). These leaflets were isolated from the bottom of the same plastic film dish in which the cells were cultured for experimental or diagnostic purposes, e.g. prenatal diagnosis or inborn errors of metabolism. The present test should be several 1000-fold more sensitive than the originally reported enzymatic method because (a) the adenosine-phosphorylase reaction is measured in the nucleoside forming direction which is by far the most active; and (b) the assay is performed with the cells and not with the culture medium. The latter is of special importance for the detection of those low-grade contamination in which most of the mycoplasma particles are attached to cell membranes.

Cell Line↗
PubMed1978

Two-dimensional thin-layer chromatography for the screening of disorders of purine and pyrimidine metabolism.

A method is presented for the two-dimensional thin-layer chromatographic screening of purines, pyrimidines and their nucleosides in the urine. Prior to chromatography, isolation of these substances from the urine is performed by anion-exchange column chromatography. Purines and pyramidines are quantitatively eluted with formic acid 0.01 M and 4 M respectively. The results of recovery and stability experiments are given. Normal excretory patterns are presented. Also results in patients with various diseases are shown: ornithine transcarbamylase deficiency, adenosine deaminase deficiency, purine nucleoside phosphorylase deficiency, adenine phosphoribosyltransferase deficiency, xanthine oxidase deficiency and hypoxanthine-guanine phosphoribosyltransferase deficiency. Finally the pattern of a patient on treatment with allopurinol is given.

ATP Phosphoribosyltransferase↗
PubMed1975

Somatic cell hybrids between mouse peritoneal macrophages and simian-virus-40-transformed human cells: II. Presence of human chromosome 7 carrying simin virus 40 genome in cells of tumors induced by hybrid cells.

Cells derived from tumors induced in "nude" mice after injection of cells that were hybrids between mouse peritoneal macrophages and simian virus 40 (SV40)-transformed human cells were found to retain the human chromosome 7 carrying the SV40 genome, and indicate that the presence of human chromosome 7 carrying the SV40 genome is responsible for the expression of the tumorigenic phenotype in the hybrid cells.

Animals↗