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Biomedical subjects

R W Watts

Publications and source records attributed to R W Watts.

At least 127 records · Page 7Linked to original sources
PubMed1977

Lymphocyte purine 5'-nucleotidase edficiency in primary hypogammaglobulinaemia.

The mean activity of purine 5'-nucleotidase (E.C.3.1.3.5) in lymphocytes was significantly lower in patients with non-familial adult onset "variable" primary hypogammaglobulinaemia than in non-hypogammaglobulinaemic control subjects. These findings suggest that 5'-nucleotidase activity is necessary for normal lymphocyte function. This may be related to its role in facilitating the transfer of newly formed purines across cell membranes by converting them from nucleotides to nucleosides. This enzyme defect may be a characteristic metabolic lesion in at least some of the patients; alternatively, it may be secondary to some other metabolic defect or plasma-membrane change.

Agammaglobulinemia↗
PubMed1977

The role of de novo purine synthesis in lymphocyte transformation.

Genetic defects in purine metabolism are associated with severe immunodeficiency. Adenosine deaminase deficiency impairs the function of both B- and T-lymphocytes whereas in purine nucleoside (inosine) phosphorylase deficiency there is more severe impairment of T-lymphocyte functions than of B-lymphocyte functions. The relative unimportance of the salvage pathway catalysed by hypoxanthine-guanine phosphoribosyltransferase is shown by the normal responses of T-lymphocytes from patients with the Lesch-Nyhan syndrome to antigenic and mitogenic stimulation. A mild deficiency of B-lymphocyte function is found in these patients. Agents inhibiting the de novo pathway of purine synthesis, including azaserine, 6-mercaptopurine and azathioprine in low doses, block the responses of normal human lymphocytes to mitogenic stimulation. These observations emphasize the importance of the de novo pathway of purine synthesis in lymphocyte responses to antigenic and mitogenic stimulation. There is considerable heterogeneity in the amount of labelled uridine incorporated into human and rat lymphocytes. This does not appear to reflect only a difference between T- and B-lymphocytes

Adenine Phosphoribosyltransferase↗
PubMed1977

Inherited metabolic disease: prospects for the future in both basic and clinical research.

The birth of a child with an inherited disorder is often the beginning of a life-long problem for the whole family. About 8.5% of paediatric deaths and 4.7% of paediatric hospital admissions are due to autosomal and sex-linked recessive diseases. These figures are likely to be erroneously low because of incomplete ascertainment. The inherited metabolic diseases therefore merit study on economic as well as humanitarian grounds. Investigations of the disorders of purine metabolism have been conducted for more than a century and a half in the borderland between biochemistry and medicine, illuminating both disciplines and reflecting their separate developments. These studies are a general model for work in other branches of human intermediary metabolism. It is hoped that the basic study of the inborn errors or metabolism will expand our knowledge of the defective gene and of its product, the enzyme protein. Clinical studies should aim to improve the prenatal, postnatal and carrier-state diagnosis of these disorders, and to improve their treatment by methods which can be made practicable and generally available at the clinical level. There may be some hope for enzyme replacement in certain circumstances. The prospect for genetic modification at the clinical level is almost infinitely far away, where many would say that is should remain.

Amniotic Fluid↗
PubMed1977

Biochemical expression of the galactosemic defect in lymphocytes and the effects on glycoprotein synthesis.

Incorporation of radioactive galactose, fucose, mannose, glucosamine, and N-acetylmannosamine into acid-precipitable glycoproteins of purified peripheral blood lymphocytes froom three patients with congenital galactosemia, their healthy parents, and control subjects have been measured. In the galactosemic lymphocytes, the incorporation of galactose into acid-precipitable glycoproteins was less than 7% of values obtained with controls and the presumed heterozygotes. The incorporation of other sugars into the glycoprotein fraction did not differ significantly from normal. Attempts to demonstrate a deficiency in cell-surface galactose groups proved negative. Galactosemic lymphocytes responded well to galactose-binding mitogens and were fully sensitive to a galactose-binding toxic lectin. We conclude that a defect in the galactose-1-phosphate uridyl transferase pathway to uridine diphosphate-galactose does not affect appreciably normal carbohydrate chain assembly in galactosemic lymphocytes. However, we cannot rule out minor changes which might account for the decreased responsiveness to serotonin in an experimental animal model of galactosemia. The approaches used in this paper may be useful in detecting other inborn errors of carbohydrate metabolism.

Adolescent↗
PubMed1977

A comprehensive screening method for detecting organic acidurias and other metabolic diseases in acutely sick infants and children.

A protocol is described for the comprehensive screening of acutely ill neonates and infants for inherited metabolic diseases, with particular reference to the organic acidurias. A group of simple initial tests provide positive pointers to metabolic disorders, leading to comprehensive screening tests for the aminoacidopathies and organic acidurias. Specimen chromatograms of urinary organic acids in the normal neonate, infant, and child, obtained using the methods described, are given and compared with that from the urine of a child with previously unreported 2-hydroxyglutaric aciduria. The place of the scheme in the management of inherited metabolic disease in the perinatal period and its relationship to other screening programmes are discussed. It is estimated that use of the protocol would allow the detection of about one-half of the known inborn errors of metabolism, including the aminoacidopathies, the organic acidurias, the hyperammonaemias, and several disorders of carbohydrate metabolism, many of which present acutely in the neonate and infant.

Amino Acids↗
PubMed1977

Low Dose D-penicillamine in cystinuria.

(1) A single dose of D-penicillamine (not more than 750 mg) taken at 2200 h, together with a prescribed fluid intake of two to three litres during the waking hours, without extra drinks at night, is sufficient to keep the concentration of the urinary cystine below the saturating concentration of urine throughout the 24 h period. (2) This regime does not materially reduce the total 24 h excretion of cystine. (3) The effect of D-penicillamine is mainly seen in the urine excreted between 0200 and 0800 h. (4) This regime is provisionally recommended for the prevention of cystine stone recurrence but not for stone dissolution. Larger total amounts of D-penicillamine given in divided doses are still recommended for the latter purpose.

Adolescent↗
PubMed1976

Metabolic investigations after xylitol infusion in human subjects.

Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed.

Adult↗
PubMed1976

Use of phytohaemagglutinin stimulated lymphocytes to study effects of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency on polynucleotide and protein synthesis in the Lesch-Nyhan syndrome.

The incorporation of [14C]thymidine and [14C]uridine into the nucleoprotein, and [14C]phenylalanine into the protein by phytohaemagglutinin (PHA) stimulated lymphocytes from a patient with the Lesch-Nyhan syndrome [hypoxanthine-guanine phosphoribosyl transferase (EC 2.4.2.8 HGPRT) deficiency] and controls, was studied over 72 hours of incubation, with and without azaserine to block de novo purine biosynthesis. No difference was observed between the values obtained for Lesch-Nyhan and control lymphocytes, when PHA-stimulated without added azaserine. The percentage reduction in the incorporation of precursors into nucleoprotein and protein after PHA stimulation in the presence of azaserine was more obvious in the lymphocytes of the patient with the Lesch-Nyhan syndrome than in the controls after the shorter incubation periods at the lower rates of synthesis. Blocking the de novo purine biosynthetic pathway, in control PHA stimulated lymphocytes, inhibited transformation, whereas loss of the purine salvage enzyme HGPRT did not have this effect. These results are compatible with the view that the brain and bone-marrow damage that occur in the Lesch-Nyhan syndrome are the result of lack of HGPRT in tissues with little de novo purine biosynthetic capability. Other tissues with both pruine biosynthetic and salvage pathways are less vulnerable to the enzyme defect. Some possible mechanisms by which HGPRT deficiency could act are discussed. We suggest that inability to increase the supply of guanylic acid (GMP) in response to a mitotic stimulus may mediate the effect of HGPRT deficiency.

DNA↗
PubMed1976

Double-blind clinical trial of 5-hydroxytryptophan in a case of Lesch-Nyhan syndrome.

5-Hydroxytryptophan (5-HTP) treatment of a single case of Lesch-Nyhan syndrome showing compulsive self-mutilation, athetoid movements, and characteristic clinical biochemical picture was studied on a double-blind basis. 5-HTP or placebo was administered for seven fortnightly treatment blocks. 5-HTP produced a significant reduction of athetoid movement and a sedative effect but did not improve the patient's mood or reduce self-mutilation.

5-Hydroxytryptophan↗
PubMed1976

Metabolic investigations during xylitol infusion.

The excretion of urinary acidic metabolites by 10 patients undergoing gastric or biliary tract surgery has been studied. Five patients were infused with xylitol and 5 with glucose. Four of the xylitol-infused patients had hyperglycollic aciduria and 3 of the glucose-infused patients had hyperlactic aciduria. There was no hyperoxaluria. Four of the xylitol-infused patients excreted more tetronic acids than any of the glucose-infused patients. Threonic acid was the predominant tetronic acid excreted by most (4/5) of the xylitol-infused subjects. Erythronic acid predominated in the glucose-infused as in control ambulant non-hospitalised subjects. It is suggested that these changes point to overloading of the transketolase pathway during xylitol infusion.

Biliary Tract Diseases↗