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J T Eells

Publications and source records attributed to J T Eells.

30 records · Page 2Linked to original sources
PubMed1983

Determination of ribonucleosides, deoxyribonucleosides, and purine and pyrimidine bases in adult rabbit cerebrospinal fluid and plasma.

Purine and pyrimidine base and nucleoside levels were measured in adult rabbit cisternal CSF and plasma by reversed-phase high-performance liquid chromatography. The concentrations of bases, nucleosides, and nucleoside phosphates were similar in plasma and CSF except for the adenosine phosphates and uracil which were higher in the plasma. In plasma and CSF, adenosine levels were low (0.12 microM) and guanosine, deoxyadenosine, deoxyguanosine, and deoxyinosine were not detectable (less than 0.1 microM); inosine and xanthine concentrations were 1-2 microM and hypoxanthine concentrations were approximately 5 microM; uridine (approximately 8 microM), cytidine (2-3 microM), and thymidine, deoxyuridine, and deoxycytidine (0.5-1.4 microM) were easily detectable. In both plasma and CSF, guanine, and thymine were undetectable (less than 0.1 microM), adenine and cytosine were less than 0.2 microM, but uracil was present (greater than 1 microM). Adenosine, inosine, and guanosine phosphates were also detectable at low concentrations in CSF and plasma. These results are consistent with the hypothesis that purine deoxyribonucleosides are synthesized in situ in the adult rabbit brain. In contrast, pyrimidine deoxyribonucleosides and ribonucleosides, and purine and pyrimidine bases are available in the CSF for use by the brain.

Adenine↗
PubMed1983

Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma.

Purine and pyrimidine base and nucleoside levels were determined in adult human lumbar (CSF) and plasma by reversed-phase high performance liquid chromatography (HPLC). Guanine, thymine, cytosine and uracil were not detectable (less than 0.1 microM) in human CSF or plasma. Adenine was detectable in plasma (0.3 microM) but was not found in CSF (less than 0.2 microM). Hypoxanthine and xanthine levels in CSF were each approximately 2.5 microM. Plasma levels of hypoxanthine and xanthine were considerably lower (0.4-0.6 microM). Purine and pyrimidine ribonucleosides in human CSF were less than or equal to 0.2 microM with the exception of uridine which was present at concentrations of 2-3 microM. Although low concentrations of thymidine and deoxyuridine (0.2 microM) were present in human plasma, purine and pyrimidine deoxyribonucleosides were less than 0.1 microM in human lumbar CSF.

Chromatography, High Pressure Liquid↗
PubMed1983

Identification, development, and regional distribution of ribonucleotide reductase in adult rat brain.

The development and regional distribution of ribonucleotide reductase (EC 1.17.4.1) were determined in rat brain. Ribonucleotide reductase was partially purified by ammonium sulfate fractionation (20-40% saturation). Enzyme activity was measured by a specific radiochemical assay. This method involved the reduction of [14C]cytidine diphosphate (CDP) to [14C]deoxycytidine diphosphate with subsequent hydrolysis and separation of the product ([14C]deoxycytidine) from substrate ([14C]cytidine) by Dowex-1-borate ion-exchange chromatography. The specific activity of ribonucleotide reductase in whole brain of newborn rats was 3.78 +/- 0.55 units (pmol/h)/mg protein (SEM; n = 6) and declined to 0.17 +/- 0.01 units/mg protein (n = 7) at 10-12 weeks of age, with a further decline to 0.11 +/- 0.01 units/mg protein (n = 3) at 1 year. Ribonucleotide reductase activity in rat liver decreased from 4.58 +/- 0.62 units/mg protein (n = 3) in newborn animals to 0.06 +/- 0.01 units/mg protein (n = 7) at 10-12 weeks and was present at trace levels at 6 months of age. The decline in specific activity with age was not due to a change in the Km for CDP. The Km for CDP in brain of newborn and adult rats was 80-90 microM. In 10- to 12-week-old rats, the specific activity of ribonucleotide reductase was similar in the various regions of the brain tested except for the brainstem, which had 50% lower specific activity than the whole brain. These results indicate that ribonucleotide reductase activity is present and widely distributed in adult rat brain.

Aging↗
PubMed1983

Methanol toxicity in the monkey: effects of nitrous oxide and methionine.

Methanol poisoning in monkeys and humans is characterized by the development of formic acidemia, metabolic acidosis and ocular toxicity. Formate, the metabolite associated with the toxicity of methanol, is oxidized to carbon dioxide by a tetrahydrofolate-dependent pathway. Nitrous oxide treatment was used to inhibit the tetrahydrofolate-generating enzyme, 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase, E.C. 2.1.1.13.), to delineate the role of this enzyme in regulating formate oxidation in the monkey. The importance of methionine in the regulation of formate oxidation in the monkey also was evaluated. Nitrous oxide inhibited the oxidation of formate generated from the metabolism of methanol (1 g/kg i.p.) in the monkey, resulting in the development of severe metabolic acidosis and high blood formate levels in these animals compared with air-breathing monkeys administered the same dose of methanol. Treatment of nitrous oxide-exposed monkeys with repetitive doses of methionine (100 mg/kg 10, 12 and 14 hr after methanol) reversed the effects of nitrous oxide on formate oxidation, resulting in a marked decrease in blood formate levels and an increase in the rate of [14C]O2 formation from methanol. Methionine treatment also reversed the development of metabolic acidosis and bicarbonate depletion observed in nitrous oxide-exposed monkeys. These results indicate that hepatic methionine synthetase is important in the regulation of tetrahydrofolate-dependent metabolism in the monkey and that the generation of tetrahydrofolate by this enzyme is a major factor in determining the sensitivity of a species to methanol poisoning.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1981

Methanol poisoning and formate oxidation in nitrous oxide-treated rats.

Formic acid does not accumulate in the rat after the administration of methanol as it does in methanol-poisoned humans and monkeys. In addition, rats do not manifest the metabolic acidosis and ocular toxicity characteristic of methanol intoxication in primates. Nitrous oxide treatment was used to inhibit 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase, EC 4.2.99.10) in order to delineate the role of this enzyme in regulating the metabolism of formate in rats and in determining the sensitivity of this species to methanol intoxication. Nitrous oxide treatment resulted in a decrease in hepatic levels of nonmethylated tetrahydrofolate forms and an increase in 5-methyltetrahydrofolate. Rats treated with nitrous oxide exhibited a marked decrease in the rate of oxidation of formate to carbon dioxide. The rate of disappearance of formate from the blood in these animals was decreased to half the control rate. Rats treated with nitrous oxide and administered methanol accumulated formate in blood and developed metabolic acidosis. These studies support the concept of a key role of methionine synthetase in supplying the tetrahydrofolate required for the folate-dependent oxidation of formate to carbon dioxide as well as the importance of this pathway in determining the sensitivity of a species to methanol poisoning.

Amitrole↗
PubMed1980

Methanol toxicity: treatment with folic acid and 5-formyl tetrahydrofolic acid.

After methanol administration to monkeys, an accumulation of formate in blood occurs coincident with the development of metabolic acidosis and a depletion of blood bicarbonate. Formate metabolism in monkeys depends upon and is regulated by a folate-dependent system; therefore, the effect of folic acid pretreatment and 5-formyl tetrahydrofolic acid administration on methanol toxicity was investigated. Treatment of monkeys with repetitive doses of either sodium folate (48, 24, 12, and 4 hr prior to methanol) or 5-formyl tetrahydrofolic acid (2 mg/kg at 0, 4, 8, 12, and 18 hr after methanol) resulted in a marked decrease in the levels of blood formate and an absence of both metabolic acidosis and depletion of blood bicarbonate following methanol administration. Also, 5-formyl tetrahydrofolic acid reversed methanol toxicity once it was established in the monkey. The results indicate that folate compounds decrease formate accumulation after methanol by stimulating formate oxidation or utilization and suggest a possible use for folates in the treatment of certain cases of human methanol poisoning.

Animals↗
PubMedDate not supplied

[Folic acid deficiency and increased concentrations of formate in serum and cerebrospinal fluid of patients with epidemic optical neuropathy].

We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del Río province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50% of samples and high formate concentration levels in almost 25% of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.

Alcohol Drinking↗