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D M Walford

Publications and source records attributed to D M Walford.

9 recordsLinked to original sources
PubMed1980

Globin chain biosynthesis in iron deficiency.

Globin chain synthesis was studied in seven severely iron-deficient patients before and after treatment with iron. There was no appreciable difference between the individual pre- and post-treatment alpha/beta specific activity ratios and the mean alpha/beta ratio for each group was 1.00+/-SD 0.04. In a further six untreated iron-deficient patients the mean alpha/beta ratio was 1.00+/-SD 0.04. There was therefore no evidence that iron deficiency caused a reduction in alpha/beta ratio. Three patients with beta thalassaemia trait and coexistent iron deficiency had lower alpha/beta ratios before treatment than after treatment with iron. It appeared that iron deficiency had caused reduced alpha chain synthesis in this group. Preliminary experiments have shown that the alpha/beta specific activity ratio of purified haemoglobin A is decreased in iron deficiency, indicating an increase in the size of the free alpha chain pool. It is suggested that iron deficiency may interfere with the proteolytic mechanism normally responsible for the destruction of excess alpha chains. In combined iron deficiency and beta thalassaemia trait, the resulting increase in free alpha chains might act by negative feedback to inhibit further alpha chain synthesis (Blum et al, 1970) thereby reducing the pre-treatment alpha/beta ratio.

Globins↗
PubMed1976

Alpha-thalassaemia trait in various racial groups in the United Kingdom: characterization of a variant of alpha-thalassaemia in Indians.

Patients whose red-cell indices are suggestive of thalassaemia trait, but who have a normal haemoglobin electrophoretic pattern, may be carriers of alpha-thalassaemia. A diagnosis of alpha-thalassaemia trait was made in 44 such patients, using the incorporation of [3H]leucine by reticulocytes to measure the relative rates of synthesis of the alpha- and beta-chains of adult haemoglobin. Patients with alpha-thalassaemia trait had a reduced rate of synthesis of the alpha-chains, with a mean alpha/beta specific activity ratio of 0.79+/-SD 0.07. The mean alpha/beta specific activity ratio of 20 control subjects was 1.06+/-SD 0.08. The diagnostic value of the haemoglobin H(Hb H) preparation was assessed in proven alpha-thalassaemia heterozygotes of various races. A high proportion of 'false negative' results in Indian and Negro heterozygotes indicated that the Hb H preparations is a highly unreliable screening test for use in a multi-racial population. There was no significant difference in the mean level of Hb A2 in alpha-thalassaemia heterozygotes (2.0+/0SD 0.6) compared with that of the control group (2.1+/0SD0.5). Comparison of data from patients with alpha- and beta-thalassaemia traits showed that alpha-thalssaemia trait is the milder disorder, in terms of its effects of red-cell morphology, red-cell indices and degree of globin chain imbalance. Amongst individual patients with alpha-thalassaemia trait, there was no correlation between the alpha/beta specific activity ratio and the red-blood-cell(RBC) d the red-blood-cell (RBC) count, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). This suggests that the alpha/beta ratio cannot be used to distinguish between carriers of a mild gene ('silent carriers') and carriers of a more severe disease. This is the first sutdy to characterize alpha-thalassaemia trait in Indians, in whom it appears to be a common disorder. Haematologically, alpha-thalassaemia trait in Indians is milder than that seen in Chinese and the fact that haemoglobin Bart's hydrops fetalis does not occur in Indians makes it likely that the genetics of Indian alpha-thalassaemia differ from those of the Chinese disease. A possible genetic model for Indian alpha-thalassaemia is discussed and the identification of the homozygote is seen as the first step in the determination of the underlying molecular defect.

China↗