Search PubMed⌕ Search

Biomedical subjects

R W Watts

Publications and source records attributed to R W Watts.

At least 91 records · Page 5Linked to original sources
PubMed1983

Biochemical and histopathological studies on patients with mucopolysaccharidoses, two of whom had been treated by fibroblast transplantation.

Biochemical and pathological observations on tissues from two patients with Hurler disease (mucopolysaccharidosis IH; alpha-L-iduronidase deficiency) who had been treated by fibroblast transplants as a means of enzyme replacement treatment are reported. These results and those obtained in three surgical specimens [ligamentum flavum with dura mater from a case of Scheie disease (mucopolysaccharidosis IS; alpha-L-iduronidase deficiency); a fetus with Hurler disease; and tonsil from a patient with Hunter disease (mucopolysaccharidosis II; alpha-L-idurono-2-sulphate sulphatase deficiency)] illustrate the inadequacy of routine histological processing to demonstrate the abnormal glycosaminoglycan accumulation in this group of diseases. A combined approach using histochemistry and electron microscopy enables the extent of both extracellular and intracellular involvement to be assessed. The fetus (20 wk gestation) already showed evidence of Hurler disease. The pathological appearances in both of the fibroblast-transplanted patients were those which would have been expected in patients dying with unmodified Hurler disease. There was no detectable alpha-L-iduronidase activity in the brain, liver, kidney or in fibroblasts cultured from either the transplantation sites or from remote subcutaneous sites in either of the transplanted patients. These results are discussed from the viewpoint of their bearing on the pathophysiology of the mucopolysaccharidoses and proposals for their treatment by enzyme replacement.

Adult↗
PubMed1983

Purine de novo synthesis in liver and developing rat brain, and the effect of some inhibitors of purine nucleotide interconversion.

The rate of purine de novo synthesis from sodium formate in developing rat brain falls in the late gestational stages to birth, rises again in the 1st week of life and then decreases rapidly to the 3rd week, and continues declining up to 8 weeks of life (adulthood). The changes in the overall purine biosynthetic rate with respect to time are similar to those in the activity of the rate-limiting enzyme [amidophosphoribosyltransferase (phosphoribosyl diphosphate amidotransferase; EC 2.4.2.14)]. Azaserine [O-diazoacetyl-L-serine], a known inhibitor of glutamine requiring metabolic steps, inhibits purine de novo synthesis by more than 90%. This confirms that the method used to assess purine de novo synthesis in fact does so. The effects of virazole [1-beta-ribofuranosyl-1-H,1,2,4-triazole-3-carboxamide], an inhibitor of IMP dehydrogenase (EC 1.2.1.14), and of alanosine [L-2-amino-3-(hydroxynitrosamino)propanoic acid] an inhibitor of adenylosuccinate synthetase (EC 6.3.4.4), on the rate of purine de novo synthesis were investigated in liver and brain tissue. The effect of the xanthine oxidase inhibitor allopurinol [4-hydroxypyrazolo(3,4-d)pyrimidine] was also investigated in liver tissue. The biosynthesis of the purines which were extruded into the incubation medium as well as those which remained in the tissue was studied. Only inhibitory effects were observed, and these were confined to the purines remaining in the tissue. Allopurinol was completely inert from this viewpoint. The results are compared with those of other workers using lymphoid cells, and emphasize the differences in the control of de novo purine synthesis in different tissues and under different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1983

Changes in crystal size and orientation of acidic glycosaminoglycans at the fracture site in fractured necks of femur.

The aim of this study was to try to elucidate the increased susceptibility of the neck of femur to fracture. Quantitative polarised light microscopy has been applied to fresh, undecalcified sections of samples of bone taken from the site of fracture, in specimens taken at operation from patients with fractures of the femoral neck or osteoarthritic femoral heads or from the equivalent site from otherwise normal subjects at necropsy. In all 21 specimens of fractured necks of femur, but in none of the other specimens, relatively large crystals (up to 2.5 X 0.5 micrometres) were found close to the site of fracture; the properties of these crystals were compatible with their being apatite. Measurement of the natural birefringence of the collagen showed no difference in the orientation of the collagen in all three types of specimen. However, the orientation of acidic glycosaminoglycans, measured by the birefringence of alcian blue bound to these moieties, was 45 per cent lower in the specimens from fractured necks of femur than in the other specimens, even though the total content of acidic glycosaminoglycans was unchanged. Although the decreased orientation was most marked close to the site of fracture, it was still apparent 15 millimetres from that site. These changes were unlikely to be simply the sequelae of fracture since they were not found in traumatic fractures of other bones. Thus it is conceivable that changes in the orientation of the ground substance allow formation of relatively large crystals of apatite and that such crystals, in the microcrystalline mass of apatite, are the cause of the increased fragility of such bones.

Aged↗
PubMed1982

Serum methionine and hepatic enzyme activity in anaesthetists exposed to nitrous oxide.

Normal serum concentrations of methionine, leucine, isoleucine and valine have been found in 10 anaesthetists using nitrous oxide under their regular working conditions without scavenging of patients' exhaled gas. Mean inhaled concentrations of nitrous oxide ranged from 150 to 400 p.p.m. The results indicate either that there was no significant inhibition of methionine synthase (attributable to oxidation of vitamin B12 by nitrous oxide) or that methionine concentrations were maintained by dietary intake or by the alternative betaine pathway of methylation of homocysteine. In either case, anaesthetists working under these conditions should not be at risk from reduced methionine concentrations. We also report normal serum activities of aspartate transaminase and gamma glutamyl transpeptidase.

Adult↗
PubMed1982

Activities of enzymes involved in purine metabolism and some related adenine nucleotide concentrations of leucocytes in renal failure.

We have studied purine metabolism in mononuclear and polymorphonuclear cells from uraemic patients using microradiochemical enzyme assays and high-pressure liquid chromatography. In mononuclear cell lysates the mean activities of adenosine deaminase (EC 3.5.4.4) and 5'-nucleotidase (EC 3.1.3.5) were significantly diminished. The activities of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), adenine phosphoribosyltransferase (EC 2.4.2.7), and hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were not significantly different in the two groups. The activities of adenosine deaminase and adenine phosphoribosyltransferase were reduced in the polymorphonuclear cell lysates. No clear differences emerged in the concentration of adenine nucleotides in the mononuclear cells. The significance of these changes, which are less marked than those in erythrocytes, is discussed with reference to the immunodeficiency associated with uraemia.

Adenine Nucleotides↗
PubMed1981

Urinary organic acids in normal full-term newborns aged 1-7 days.

urinary organic acid metabolite excretion patterns in normal newborns aged 1 to 7 days were analysed by GC and MS. Statistical analysis showed significantly different relationships between metabolite excretion, age, sex and feed. The data provide a necessary background for the diagnosis of inborn errors or organic acid metabolism.

Aging↗
PubMed1981

Effect of renal failure on erythrocyte purine nucleotide, nucleoside and base concentrations and some related enzyme activities.

1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes. 2. The mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant elevations of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and adenosine deaminase (EC 3.5.4.4) but not of adenine phosphoribosyltransferase (EC 2.4.2.7) and ribosephosphate pyrophosphokinase (phosphoribosylpyrophosphate synthetase; EC 2.7.6.1) activities were demonstrated. However, there was an overlap between results from patients with renal failure and normal (control) subjects. Erythrocyte phosphoribosylpyrophosphate levels were also unchanged. 3. Erythrocyte nucleotide concentrations especially those of inosine were raised in renal failure. 4. The plasma inosine was reduced in renal failure. 5. The significance of these changes is discussed.

Adolescent↗
PubMed1981

A newly recognized syndrome of connective tissue dysplasia in siblings (previously described as a variant of Morquio disease).

Siblings (one male and one female) with a striking combination of multiple skeletal abnormalities, hypermobility in some joints with a restricted range of movements in others, mesodermal dysgenesis of the iris and cutaneous atrophy with thin skin, multiple telangiectases, shallow ulcers, and café au lait lesions are described. The patients were reported in early childhood as cases of Morquio disease (mucopolysaccharidosis IV) with previously unrecognized skin changes. The results of specific enzyme assays exclude a diagnosis of both of the known biochemical types of Morquio disease; the evolution of their disease and the present clinical findings are in accord with this. These patients do not correspond to any of the other mucopolysaccharidoses, mucolipidoses or sphingolipidoses. We have been unable to classify them as examples of other inherited skeletal dysplasias and we suggest that they probably have an, as yet unidentified, recessively inherited disorder of collagen.

Adolescent↗
PubMed1980

Trimethylaminuria.

We describe the case of an otherwise healthy 7-year-old girl whose mother noticed that she intermittently smelt of fish. This was due to the intermittent excretion of trimethylamine which could be precipitated by choline ingestion and by eating fish. Excluding eggs, liver and salt-water fish from the diet relieved the symptom. After a standard 15 g choline load, the child's father, but not her mother, excreted amounts of trimethylamine which were intermediate between those excreted by the patient and normal control subjects.

Animals↗
PubMed1980

D-2-hydroxyglutaric aciduria: case report and biochemical studies.

A patient with protein-losing gastroenteropathy and egg allergy has been shown to have a previously unrecognized organic aciduria, D-2-hydroxyglutaric aciduria. The observations made are consistent with an inherited metabolic disorder in the catabolism of 5-aminolaevulinate possibly due to deficient activity of a specific D-2-hydroxyglutarate dehydrogenase.

Aminolevulinic Acid↗
PubMed1980

Activities of amidophosphoribosyltransferase (EC2.4.2.14) and the purine phosphoribosyltransferases (EC2.4.2.7 and 2.4.2.8), and the phosphoribosylpyrophosphate content of rat central nervous system at different stages of development--their possible relationship to the neurological dysfunction in the Lesch-Nyhan syndrome.

(1) This communication reports the amidophosphoribosyltransferase (PRPP-At; EC2.4.2.14), hypoxanthine phosphoribosyltransferase (HPRT; EC2.4.2.7) and adenine phosphoribosyltransferase (APRT; EC2.4.2.8) activities and the phosphoribosylpyrophosphate (PRPP) content of rat brain at different stages of development. The results are not age-related in the foetal and neonatal animals and the data for whole brain homogenates are similar to the average results for the individual regions of the brain at the same stage of development. (2) The enzyme activities and PRPP content are similar in the different regions of the rat central nervous system. PRPP-At has the lowest activity of the 3 enzymes studied and this decreases gradually from birth until 8 weeks. HPRT is the most active of the three enzymes, its activity increases markedly between birth and the end of the third week of life. The time course of these changes shows only minor differences between the regions of the brain studied. The ratio of HPRT activity to PRPP-At activity increases from age 1 week in all parts of the rat brain. (3) The APRT activities in rat brain are intermediate between those of PRPP-At and HPRT and essentially steady except for a decrease in the cerebellum during the first 3 weeks of life. (4) The PRPP concentrations in rat brain decrease between birth and the end of the 3rd week of life. (5) The systemic tissues examined have PRPP-At, HPRT and APRT activities. The relationship between the activities of the different enzymes appears to be characteristic of the tissue concerned. (6) Correlating the observed time course of the changes in the ratio of hypoxanthine phosphoribosyltransferase activity to amidophosphoribosyltransferase activity in the rat with other workers' data on changes in the rate of DNA accretion in human brain during development indicates that the main increase in this ratio is after the major bursts of neuroblast and neuroglia proliferation. We suggest that the neurological dysfunction in the Lesch-Nyhan syndrome is due to lack of a purine derivative with a physiological or neuropharmacological function, rather than to an effect of the biochemical lesion on brain morphogenesis.

Adenine Phosphoribosyltransferase↗