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Biomedical subjects

S S Bottomley

Publications and source records attributed to S S Bottomley.

35 records · Page 2Linked to original sources
PubMed1981

The diagnosis of acute intermittent porphyria. Usefulness and limitations of the erythrocyte uroporphyrinogen I synthase assay.

In acute intermittent porphyria (AIP) the inherited metabolic defect residues in a partial enzyme deficiency at the uroporphyrinogen I synthase (URO-S) step of heme biosynthesis. Assay of this enzyme in erythrocytes is increasingly used for diagnosis of the genetic defect. Erythrocyte URO-S activity was measured by three laboratories in members of 14 AIP kindreds and found helpful for diagnosing the asymptomatic carrier state, since activity of the enzyme was usually distributed bimodally. However, a definite diagnosis of the carrier state was not always possible with this assay: approximately 7% of a total of 340 determinations were inconclusive. Repeat enzyme assays, enzyme assays by more than one laboratory, quantitative urine porphobilinogen determinations, and studies of other family members all aided in arriving at a firm diagnosis for most of those in whom a single erythrocyte URO-S measurement was inconclusive. Because the enzyme is unstable, blood specimens should be stored frozen if immediate assay is not possible.

Acute Disease↗
PubMed1980

Bone marrow delta-aminolaevulinate synthase deficiency in a female with congenital sideroblastic anemia.

Heme biosynthesis was examined in erythroid tissue of a 4-yr-old girl with severe sideroblastic anemia since infancy, as documented by the presence of intramitochondrial deposits of iron in erythroblasts. Free red cell protoporphyrin, urinary porphyrins, and activities of erythrocyte porphobilinogen synthase, uroporphyrinogen 1 synthase, aspartate aminotransferase, and pyridoxine kinase were normal or increased. Bone marrow ferrochelatase activity was normal. Activity of bone marrow delta-aminolaevulinate (ALA) synthase was markedly reduced to 7 pmole ALA/10(6) erythroblasts/30 min (normal 127 +/- 29) but was enhanced fivefold by pyridoxal phosphate (normal 0%--25% increase). Therapy with oral pyridoxine and parenteral pyridoxal-5'-phosphate did not increase effective red cell production. The sideroblastic anemia in this patient appears to be related to a congenital defect in the initial step of heme biosynthesis.

5-Aminolevulinate Synthetase↗
PubMed1978

A new chromosome abnormality in idiopathic sideroblastic anemia: 46,XY,del11q23.

A new marker chromosome, deletion 11q23, was observed with the Giemsa banding technique in the bone marrow of a patient with idiopathic sideroblastic anemia. The abnormality was not detectable in the peripheral blood or with nonbanded chromosome studies. Nineteen of 40 cases of this disorder studied and reported to date had chromosomal aberrations, although the majority had only nonbanded karyotypes performed. This apparently high incidence of chromosomal defects and the finding in the present case indicate that more banded-karyotype analyses are needed to assess the presence of possible nonrandom cytogenetic changes in idiopathic sideroblastic anemia.

Anemia, Sideroblastic↗
PubMed1975

Diminished erythroid ferrochelatase activity in protoporphyria.

In two patients with protoporphyria the enzymatic synthesis of aminolevulinic acid and prophobilinogen in erythroid tissue was normal. Boine marrow ferrochelatase activity was less than one-fourth of the mean activity in normal control subjects. Ferrochelatase activity in peripheral blood reticulocytes was less than 10% of controls. This metabolic abnormality provides one biochemical explanation for the increased concentrations of blood protoporphyrin in protoporphyria and clarifies the apparent minimally impaired hemoglobin synthesis in the two case studies.

5-Aminolevulinate Synthetase↗
PubMedDate not supplied

Pure red cell aplasia associated with fenoprofen.

A 69-year-old man developed pure red cell aplasia after taking fenoprofen for ten months. The erythroid defect fully reversed after the drug was discontinued and could not be attributed to the patient's previously treated lung carcinoma. This case represents the third example of erythroid aplasia associated with an anti-inflammatory agent and the first instance due to fenoprofen.

Aged↗
PubMedDate not supplied

Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene.

PURPOSE: To identify mutations in families with acute intermittent porphyria, an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase. METHODS: Mutations were identified by direct solid phase sequencing. RESULTS: Two novel missense mutations E80G and T78P and three previously reported mutations, R173W, G111R, and the splice site lesion, IVS1+1, were detected, each in an unrelated proband. The causality of the novel missense mutations was demonstrated by expression studies. CONCLUSION: These findings provide for the precise diagnosis of carriers in these families and further expand the molecular heterogeneity of AIP.

Amino Acid Substitution↗