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Biomedical subjects

R W Watts

Publications and source records attributed to R W Watts.

At least 145 records · Page 8Linked to original sources

Urinary organic acids in man. I. Normal patterns.

We studied qualitative pattern of urinary acidic metabolites excreted by normal persons. The results provide a basis on which to compare results for patients with potentially abnormal organic acidurias. A series of urinary polyhydroxy (aldonic and deoxyaldonic) acids has been identified. Most of these compounds have not been previously reported in human urine, except in connection with the present work, and are additional to the previously recognized urinary organic acids, which were also observed. Possible metabolic origins of some of the acids are briefly discussed.

Adolescent↗

Urinary organic acids in man. II. Effects of individual variation and diet on the urinary excretion of acidic metabolites.

We have assessed individual variations in urinary acidic metabolite excretion and the effects of extreme alterations in dietary composition on these metabolites in selected normal persons who we considered representative of the general ambulant normal population. Extreme dietary alterations produced relatively small changes in the patterns or amounts of metabolite excretion, but large individual within-subject variations were observed. Our results indicate that variation in the ranges of excretion for the normal population mainly depend on individual metabolic variations rather than on dietary factors, and provide a basis for the assessment of the normal ranges determined from population surveys. Our results are discussed in relation to previous studies on the variability of urinary acidic metabolite excretion in man.

Adult↗

Urinary organic acids in man. III. Quantitative ranges and patterns of excretion in a normal population.

We studied the urinary excretion of organic acids by normal human subjects in an ambulant normal population, chosen without conscious bias. Quantitative ranges and frequency distribution patterns of excretion are reported, as a basis on which to compare results obtained for patients whose clinical condition suggests that their excretion values may be abnormal. The quantitative valuse we observed enable the relative significance of different urinary anionic metabolites to be assessed, including the recently identified aldonic and deoxyaldonic acids. The frequency distribution patterns observed are discussed briefly.

Adolescent↗

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↗

Depression of bone marrow colony formation in gold-induced neutropenia.

Bone marrow culture in semi-solid agar was used to assess the proliferative activity and the response to sodium aurothiomalate of the myeloid precursor cells from patients during and after recovery from neutropenia associated with the use of this drug. Colony formation was reduced during the neutropenia and returned to normal after recovery. The rheumatoid process itself did not impair colony formation even in patients with Felty's syndrome. Sodium aurothiomalate inhibited colony formation by normal marrow in a dose-dependent manner. Bone marrow colonies from patients who had recovered from neutropenia induced by sodium aurothiomalate were not abnormally sensitive to the inhibitory effect of the drug in vitro. The metabolism of gold is probably altered in a small proportion of patients, which causes high local concentrations within the bone marrow leading directly to marrow depression.

Adult↗

Abnormal organic acidurias in mentally retarded patients.

Urine specimens from 1778 mentally retarded patients and 420 age and sex matched non-retarded controls selected from a general practice have been analysed for non-amino organic acids by a quantitative extraction and gas chromatographic method. The compounds were identified by combined gas chromatography and mass spectrometry. Approximately 5% of the patients had an abnormal organic aciduria. The frequency of abnormalities was slightly higher (about 7%) in a group of 248 severely subnormal children, but not in cases with a family history of mental retardation, retarded sibs, or whose parents were consanguineous. The most frequently observed abnormalities were phenylalanine metabolites in cases of phenylketonuria (about 1%), increased excretion of benzoic acid (about 1%), and increased excretion of 2-oxoglutaric acid with or without raised urinary citric-acid levels (about 1%). The biochemical and clinical significance of these findings is being further investigated.

Acidosis↗

Methionine adenosyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase activity of rat liver subcellular particles, human blood cells and mixed white cells from rat bone marrow.

1. Methionine adenosyltransferase (ATP:L-methionine-S-adenosyl transferase, EC 2.5.1.6), cystathionine beta-synthase F1L-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] and cystathionine gamma-lyase [L-cystathionine cysteine-lyase (deaminating), EC 4.4.1.1] activities were found only in the cytosol fraction of rat liver cells. None was found in the mitochondrial or endoplasmic reticulum fractions as judged by the distribution of marker enzymes on a density gradient after centrifugation of the cytoplasmic fraction of a liver homogenate, or in a preparation of liver cell nuclei. 2. Polymorphs, lymphocytes (with admixed monocytes) and mixed bone marrow white cells contained no methionine adenosyl transferase, cystathionine beta-synthase or cystathionine gamma-lyase activities. 3. The possible bearing of these results on the problem of abnormal cystine storage in cystinosis is briefly discussed.

Animals↗

Some biochemical effects of chloral hydrate in an infant with a tyrosinemia-like syndrome.

An infant with a combination of clinical and biochemical features resembling those found in hereditary tyrosinemia ("inborn hepatorenal dysfunction with tyrosyluria") but with spontaneous recovery is described briefly. The child also had severe congenital hydrocephalus, and was being given chloral hydrate. She was not treated by restriction of dietary phenylalanine and tyrosine. The abnormal aromatic aciduria was unaltered by ascorbic acid administration. The results of loading tests with phenylalanine, tyrosine, and sodium 4-hydroxyphenylpyruvate are compatible with the existence of a partial block in the oxidation of 4-hydroxyphenylpyruvate to homogentisate which was exacerbated by administering chloral hydrate.

4-Hydroxyphenylpyruvate Dioxygenase↗