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Biomedical subjects

J F Henderson

Publications and source records attributed to J F Henderson.

At least 73 records · Page 4Linked to original sources
PubMed1977

Studies of the relationship between adenosine deaminase and immune function.

The relationship between adenosine deaminase deficiency and immunologic responsiveness was studied in mice treated in vivo with deoxycoformycin to produce very low levels of adenosine deaminase activity in tissues. Effects of such treatment on thymocyte response to concanavalin A in vitro and on mixed cultures of splenic cells were determined. Under the conditions used, inhibition of adenosine deaminase by deoxycoformycin had no effect on the viability or responsiveness of either thymocytes or splenic cells.

Adenosine Deaminase↗
PubMed1977

Effects of ethidium and isometamidium on adenosine triphosphate catabolism and purine nucleotide synthesis in Ehrlich ascites tumor cells in vitro.

Ethidium and isometamidium induce the breakdown of intracellular adenosine triphosphate in Ehrlich ascites tumor cells incubated in vitro. Ethidium induces appreciable adenosine triphosphate breakdown only when cells are incubated without glucose, whereas isometamidium produces this effect both in the presence and absence of glucose. In cells treated with isometamidium, purine nucleoside monophosphates accumulate, whereas these are mostly dephosphorylated when ethidium is used. Both ethidium and isometamidium inhibit purine nucleotide synthesis and incorporation of precursors into nucleic acids, although the magnitudes of these effects varied with the precursor used. Isometamidium inhibited the conversion of inosinate to adenine and guanine nucleotides, and both compounds partially inhibited the accumulation of phosphoribosyl pyrophosphate.

Adenine↗
PubMed1977

Consequences of inhibition of guanine nucleotide synthesis by mycophenolic acid and virazole.

Mycophenolic acid and virazole are inhibitors of inosinate dehydrogenase and produce growth inhibition and loss of viability in cultured murine lymphoma L5178Y cells. Treatment with 1 muM mycophenolic acid produced the following changes in concentrations of acid-soluble nucleotides: (a) guanosine triphosphate decreased to less than 10% of control within 2 hr; (b) uridine triphosphate and cytidine triphosphate concentrations increased markedly; (c) adenosine triphosphate did not change; (d) deoxyguanosine triphosphate decreased; and (e) thymidine triphosphate increased. DNA synthesis was inhibited by 90% within 2 hr, whereas the incorporation of adenosine into RNA and of leucine into protein were much less affected. Virazole (100 muM) produces similar effects. These biochemical effects of mycophenolic acid, as well as its effects on cell growth, can be prevented by addition of guanylate to the medium. Mycophenolic acid treatment also appears to cause breakdown of high-molecular-weight DNA.

Adenosine Triphosphate↗
PubMed1976

Uric acid lithiasis associated with altered kinetics of hypoxanthine-guanine phosphoribosyltranferase.

1. A patient is described who had uric acid calculi which obstructed both kidneys. Serum uric acid was 34 mg/100 ml upon admission to hospital, and evidence of precipitation of uric acid in joints was obtained. 2. Total activity of hypoxanthine-guanine phosphoribosyltransferase in erythrocytes lysates from this patient was 44% of normal. Kinetic studies revealed that the apparent Michaelis constant of this enzyme for phosphoribosyl pyrophosphate was elevated 15-fold, while these values for hypoxanthine and guanine were in the normal range.

Adult↗
PubMed1976

Relative importance of alternative pathways of purine nucleotide biosynthesis in Ehrlich ascites tumor cells in vivo.

Several alternative pathways of purine nucleotide synthesis coexist in cells and the relative importance of each pathway for maintaining purine nucleotide concentrations in cells have been studied. Specific inhibitors were used to block these synthetic routes in Ehrlich ascites tumor cells in vivo and the effect of inhibiting each pathway was evaluated by measuring intracellular purine nucleotide concentrations by high-speed liquid chromatography. The results of this study indicate that adenosine triphosphate and guanosine triphosphate concentrations of Ehrlich ascites tumor cells are maintained primarily by purine biosynthesis de novo although other pathways do make significant contributions.

AMP Deaminase↗
PubMed1976

Utilization of dietary nucleic acid purines for nucleotide and nucleic acid synthesis in the mouse.

Three preparations of radioactive yeast nucleic acids were fed to mice. One was labeled predominantly in the guanine moiety, one was labeled predominantly in the adenine moiety, and in one adenine and guanine were labeled equally. Most of the nucleic acid purines produced by digestion were excreted in the urine. However, a small amount was utilized for nucleotide and nucleic acid synthesis in the mouse tissues. Small intestine, liver and skeletal muscle contained most of the purines that were retained in the tissues. Dietary nucleic acid adenine appeared to be utilized somewhat more efficiently than was dietary nucleic acid guanine.

Adenine↗
PubMed1976

Relationships between nucleoside triphosphate pyrophosphohydrolase activity and inosine triphosphate accumulation in human erythrocytes.

The relationship between nucleoside triphosphate pyrophosphohydrolast (NTPH) (EC 3.6.1.19) activity in erythrocyte lysates and accumulation of radioactive inosine triphosphate (ITP) in human erythrocytes incubated in vitro with [14C]hypoxanthine, was studied in 93 humans. When ITP accumulation, expressed as percentage of total radioactive nucleotides, was plotted against NTPH specific activity, an inverse relationship was found to exist. A continous spectrum of NTPH specific activities and ITP accumulation values exists in the human population and the relationship between these two parameters follows the relationship of substrate concentration to enzyme activity predicted by Michaelis-Menten enzyme kinetics. One interpretation of these data is that the ITP concentration in human red blood cells is controlled by the degradation of ITP to IMP and pyrophosphate catalyzed by NTPH.

Erythrocytes↗
PubMed1976

Inhibitors of hypoxanthine metabolism in Ehrlich ascites tumor cells in vitro.

One hundred and sixty-one purine analogs and derivatives were tested for their ability to inhibit ten parameters of purine metabolism in Ehrlich ascites tumor cells incubated in vitro with radioactive hypoxanthine. Sixty-seven compounds were inhibitory against at least one parameter and 30 were inhibitory against two or more.

Adenosine Diphosphate↗
PubMed1975

Individual variation in inosine triphosphate accumulation in human erythrocytes.

Erythrocytes from 5% of a normal population accumulated relatively high amounts of radioactive inosine triphosphate (i.e., greater than 70 nmoles/10(10) cells in 2 hr) when they were incubated with [14C]hypoxanthine. The incidence of this characteristic in a mentally retarded population was 16%. Inosine triphosphate was synthesized from [14C]hypoxanthine, but not from [14C]adenine or [14C]guanine. The metabolism of [14C]adenine and [14C]guanine was the same in erythrocytes that accumulated "normal" and "high" amounts of inosine triphosphate. Inosine triphosphate did not accumulate in leukocytes.

Adenine↗
PubMed1975

Studies of the regulation of purine nucleotide catabolism.

Ehrlich ascites tumor cells containing radioactive ATP were incubated in vitro with a range of concentrations of 2-deoxyglucose in order to produce different rates of ATP catabolism. Concentrations of all radioactive products of ATP catabolism were measured, and apparent rates of adenylate deaminase and inosinate dehydrogenase and of adenylate and inosinate dephosphorylation were calculated. It was concluded that these processes were reggulated primarily by the rate of formation of substrate, and to a lesser extent in some cases, by substrate concentration. No evidence was obtained for regulation of these processes by the concentration of ATP. The deoxyglucose-induced catabolism of radioactive GTP was also studied. When ATP catabolism was induced by incubation with 2,4-dinitrophenol, time courses of accumulation of purine nucleoside monophosphates and rates of alternative pathways of their metabolism were quite different than when deoxyglucose was used.

Adenosine↗
PubMed1975

Effects of hormones and drugs on phosphoribosyl pyrophosphate concentrations in mouse liver.

Concentrations of phosphoribosyl pyrophosphate (PP-ribose-P) in mouse liver were studied as a function of time of day and following injection of a number of metabolites and drugs. A twofold diurnal variation in liver PP-ribose-P concentration was observed. Liver PP-ribose-P concentrations were elevated following injection of glucagon, insulin, epinephrine, and ethylaminothiasiazole.

Animals↗
PubMed1975

Consequences of methotrexate inhibition of purine biosynthesis in L5178Y cells.

Addition of 1 muM methotrexate to cultures of L5178Y cells results in an initial inhibition of thymidine, uridine, and leucine incorporation into acid-insoluble material followed, after about 10 hr, by a partial recovery in the extent of incorporation of these precursors. Acid-soluble adenosine triphosphate and guanosine triphosphate concentrations are greatly reduced initially, but guanosine triphosphate concentrations appear to recover partially by 10 hr. Acid-soluble uridine triphosphate and cytidine triphosphate concentrations initially increase after methotrexate treatment but then, with time, they too decline. Hypoxanthine and guanine are more effective than is adenine in overcoming the methotrexate-induced inhibition of thymidine incorporation. These results suggest that, in the presence of methotrexate, guanine nucleotides become limiting for nucleic acid synthesis before adenine nucleotides do. The block of purine de novo synthesis in L5178Y cells by methotrexate is almost complete and is not reversed with time. This suggests that the additional purine nucleotides that are available for nucleic acid synthesis 8 to 10 hr after addition of methotrexate are being derived from nucleic acid breakdown. Consistent with this is the observed reduction in the number of polyribosomes and hence, presumably in messenger RNA levels.

Adenine↗