Purine metabolism studied with high-pressure liquid chromatography [proceedings].
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Biomedical subjects
Publications and source records attributed to R A Harkness.
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The lactoperoxidase (LPO) activity in guinea-pig milk and saliva has been investigated in sows suckling normal young, and young orally infected with Escherichia coli. There was a 5-fold increase in activity in milk during the 3--4 weeks of lactation; infection of the young did not alter this. There was no comparable increase in lactoperoxidase activity of saliva during this same period, either in the infected or non-infected group. The antibacterial activity of milk from sows suckling normal young increased with the lactoperoxidase, and this bactericidal activity could be reversed by LPO inhibitors such as penicillamine and cysteine but not by addition of sufficient iron to saturate the lactoferrin. In milk from sows suckling infected young, bacteriostatic activity occurring in samples from about 14 days after infection needed iron or both iron and penicillamine (or cysteine) for reversal, indicating that both the antibody-lactoferrin system and the LPO system may be involved in the infected state.
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An elevation in salivary peroxidase activity has been found about the time of ovulation in 14 menstrual cycles in a total of six women. This peak coincided with the ovulatory luteinizing hormone (LH) and oestrogen peak in the four cycles in which endocrine studies were performed. Rises in some polymorphonuclear neutrophil leucocyte enzymes were also seen around ovulation. The possible use of changes in salivary peroxidase as a method for detection of ovulation is discussed.
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1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme.
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A patient with sea-blue histiocytosis in spleen and bone marrow with an accompanying hyperlipidaemia is described. The hyperlipidaemia was due to an increase in "free" cholesterol, lecithin, and triglycerides. Despite these findings lecithin-cholesterol acyl transferase activity was normal. Although the precise biochemical defect was not identified, there was a failure of transport of cholesterol from chylomicrons in vitro. We propose that the sea-blue histiocyte is a marker, in some cases, of abnormal lipid metabolism.
Adenosine deaminase activity (ADA) has been estimated in human tissues. Levels in the thymus during childhood were very much higher than in any of the other 6 tissues studied. Intermediate activities were obtained from spleen and lymph nodes and also skin. Cerebral cortex, liver and kidney had relatively low levels. ADA activity in lymphocytes from peripheral blood was significantly increased after antigenic stimulation by TAB immunization. The available evidence appears to be consistent with T-lymphocyte growth and development in the thymus being dependant on ADA.
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Doses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete. The administration of the drug has been checked and its metabolism studied from the pattern of urinary metabolites.
The clinical and biochemical findings are described in 2 brothers who had intermittent hypoglycaemia generally precipitated by the "stress" of infection. Both were tall and pigmented. Both boys showed a failure of adrenocortical response to ACTH which was progressive in the eldest boy. The diagnosis of familial glucocorticoid deficiency (hereditary adrenocortical unresponsiveness) was confirmed by the absence of electrolyte imbalance even on a low sodium diet, and by very high levels of ACTH in plasma. High levels of deoxycorticosterone (DOC) were found in both children with normal levels of other plasma corticosteroids. It is suggested that the high levels of DOC may be in some way related to the apparent persistence of a "fetal" type of adrenocortical steroid biosynthesis for 18 months or more in these boys. After the diagnosis, established by relatively simple methods, treatment with cortisone acetate has 0een highly effective.
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