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Biomedical subjects

R E Gale

Publications and source records attributed to R E Gale.

46 records · Page 3Linked to original sources
PubMed1993

Frequency of clonal remission in acute myeloid leukaemia.

Analysis of X-chromosome inactivation patterns in females has been used to assess clonality of various tumours and for prenatal diagnosis of X-linked disorders. Studies with these methods in acute myeloid leukaemia suggest that a significant proportion of cases have clonal remissions (ie, persistence of the malignant clone), which may represent return to a preleukaemic state. We therefore analysed X-chromosome inactivation patterns with differential methylation patterns of heterozygotes for three DNA probes, HPRT, PGK, and M27 beta, in leukaemic patients and normal controls. As expected, blast cells from 67 of 68 analysable samples (99%) were monoclonal or had a skewed X-inactivation pattern. A skewed pattern in remission was also found in 26 of 77 patients (34%), proportion only slightly greater than control (16/75, 21%). In 7 of 10 patients with a skewed pattern in myeloid cells there was similar skewing in the T cells, which is compatible with the concept of a constitutively skewed X-chromosome inactivation pattern of haemopoietic cells in these patients. Our study illustrates the difficulty of interpreting clonality in individual tumour samples and emphasises the importance of comparisons with non-malignant tissue of the same cell type from that individual and from normal control populations.

Acute Disease↗
PubMed1992

Assessment of X-chromosome inactivation patterns using the hypervariable probe M27 beta in normal hemopoietic cells and acute myeloid leukemic blasts.

The value of the hypervariable X-linked probe M27 beta for use in the analysis of X-chromosome inactivation patterns in normal blood and bone marrow cells and in the assessment of clonality in acute myeloid leukemia (AML) blast cells has been determined. By electrophoresing samples for 30 h, heterozygosity of the M27 beta locus was demonstrable in 324/415 females (78%) and this value could be increased to 93% by electrophoresing for 50 h. Determination of the X-chromosome inactivation patterns in blood and bone marrow samples from hematologically normal females was possible in approximately 90% of heterozygous individuals. The X-chromosome inactivation ratios obtained with M27 beta were comparable with phosphoglycerate kinase or hypoxanthine phosphoribosyl transferase in 46 individuals heterozygous for one of these genes in addition to M27 beta. The results obtained were closely correlated (r = 0.89). In 21 of 35 (60%) AML blasts, however, there was hypermethylation of the M27 beta locus and clonal analysis was not possible. Hypermethylation was not related to FAB type.

Bone Marrow Cells↗
PubMed1991

X-chromosome inactivation patterns using HPRT and PGK polymorphisms in haematologically normal and post-chemotherapy females.

Clonal analysis using X-chromosome inactivation patterns of the hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) genes has been used in the assessment of haematological malignancies. In many analyses normal haemopoietic tissue or constitutive DNA from each individual has not been readily available and it has been assumed that when the ratio of the percentage of the two alleles remaining after differential methylation enzyme digestion is greater than 3/1 then an oligoclonal/monoclonal population of cells is present. We report here in a study of 65 haematologically normal females informative for HPRT or PGK that 15 (23%) had a skewed Lyonization pattern with clonal analysis ratios greater than 3/1. No correlation was observed between age and the X-chromosome inactivation pattern to suggest the detection of pre-malignant clonal states. The incidence was similar in 23 females who had received conventional combination chemotherapy, with six women (26%) having a ratio greater than 3/1. In the majority of individuals therefore, conventional chemotherapy does not appear to alter the patient's X-chromosome inactivation pattern. These results indicate that caution must be exercised in interpreting the results of clonal analysis of any given individual.

Adolescent↗
PubMed1980

Oxygen dissociation curve in Eales's disease.

The oxyhaemoglobin dissociation curve (ODC) was investigated in 15 patients with Eales's disease and 11 controls to test the hypothesis that Eales's disease is caused by retinal hypoxia secondary to impaired oxygen release from the blood. Patients with the peripheral form of Eales's disease did not have any significant difference in the P50 values when compared with the controls. However, the P50 values were significantly lower (P < 0.005) for the patients with mixed retinopathy. This degree of increased oxygen affinity is not physiologically significant but may reflect an intrinsic abnormality of the red cells in these cases.

Adult↗
PubMed1977

Haemoglobin Radcliffe (alpha2beta299(Gi)Ala): a high oxygen-affinity variant causing familial polycythaemia.

Three members of an Oxfordshire family have polycythaemia. In each case their whole-blood oxygen affinity is increased. This is due to a previously undescribed haemoglobin variant which has been named haemoglobin Radcliffe (alpha2beta299(Gl)Ala). In addition to having a high oxygen affinity haemoglobin Radcliffe shows virtually no haem-haem interaction and a diminished Bohr effect. It is synthesized at the same rate and is as stable as haemoglobin A. X-ray analysis indicates that crystals of deoxyhaemoglobin Radcliffe are isomorphous with those of deoxyhaemoglobin A. Solutions of haemoglobin Radcliffe were also studied by high-resolution proton nuclear magnetic resonance spectroscopy. The structure/function relationships of haemoglobin Radcliffe are discussed in the light of these studies.

Adult↗