Biomedical subjects
Publications and source records attributed to S G Welch.
Evidence is presented that two levels of glycosylated haemoglobin can be defined which when exceeded indicate respectively the presence of diabetes mellitus and a significant risk for the development of microvascular complications, as judged by current glucose tolerance test criteria for such risk.
Erythrocyte NAD(P)H2 glutathione oxidoreductase (EC 1.6.4.2.) activation coefficients (EGR AC) and D-glucose-6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49 (G-6-PD) activities were measured in 155 West African women to determine whether heterozygous G-6-PD deficiency produces false negative results in the EGR test for riboflavin deficiency. A positive correlation was found between EGR AC and G-6-PD activity demonstrating that heterozygous G-6-PD deficiency does result in abnormally depressed EGR AC values when G-6-PD activity is significantly reduced. However, heterozygous deficient genotypes with normal G-6-PD activity showed undepressed EGR AC values. These results indicate that, in its present form, the EGR test is not a suitable index of riboflavin status in subjects whose G-6-PD activity is less than 9 IU/g Hb when measured by the WHO-37 degrees assay.
A total of 701 individuals from a village in The Gambia, West Africa were tested for serum alpha 1-antitrypsin phenotypes by isoelectric focusing in thinlayer polyacrylamide gels (pH 4--5). A new variant allele, PiGAM, was discovered at a polymorphic frequency (0.0642), and the inheritance of the variant phenotype was confirmed by family studies. The variant was not found to be associated with any decrease in serum alpha 1-antitrypsin concentration. The only other allele found within this population was the common allele PiM (0.9358).
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Glutamate pyruvate transaminase (GPT) has been studied in the red cells of 46 patients with a confirmed diagnosis of polycythaemia rubra vera (PRV). The red cells of many of the patients showed low levels of enzyme activity. This activity could be restored by in vitro incubation with pyridoxal phosphate suggesting that the effect was due to low levels of B6 rather than to a primary abnormality of the GPT. Patients with the lowest levels of GPT activity were likely to have clonal chromosomal abnormalities in the bone marrow cells, particularly 20q-. Among 43 patients in whom the GPT phenotypes could be determined by an electrophoretic method there was a marked deficiency of heterozygotes. This disturbance in phenotypic expression may be related to the clonal nature of the disease in PRV, the clone showing lack of response to homeostatic controls and irregularities of gene expression.
Serum samples from 857 inhabitants of the village of Keneba, The Gambia, West Africa, were examined by means of polyacrylamide gel electrophoresis. In 203 cases no haptoglobin could be detected, whilst in the remaining 654 samples the three common haptoglobin phenotypes were found with gene frequencies of 0.651 (Hp1) and 0.349 (Hp2). The D1 transferrin variant gene was found with a frequency of 0.025. In the serum Gc system the fast variant Gc-Ab was detected, the gene frequencies being: Gc1, 0.943; Gc2, 0.044; and GcAb, 0.013.
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1. Concentrations of high-density-lipoprotein cholesterol and of glycosylated haemoglobins [HbA1(a+b+c)] were measured in non-fasting blood samples taken from 171 diabetic patients. 2. Mean concentrations of high-density-lipoprotein cholesterol were lower in men, and in patients not requiring insulin. 3. There was no correlation between concentrations of high-density-lipoprotein cholesterol and of HbA1(a+b+c) in the patients as a whole, but a significant positive correlation was found between these values in male diabetics not requiring insulin. 4. Changes in the concentrations of HbA1(a+b+c) were not correlated with changes in concentrations of high-density-lipoprotein cholesterol.
A total of 637 individuals from the rural village of Keneba in The Gambia, West Africa, have been typed for red cell PGM using isoelectric focusing (pH 5--7) in polyacrylamide gels. Eight different phenotypes have been detected. The frequency of the four alleles at the PGM1 locus was found to be PGM1+(1) 0.795, PGM1-(1) 0.053, PGM2+(1) 0.133, AND PGM2-(1) 0.019. A study of the PGM phenotypes in 89 families confirmed the simple Mendelian codominant inheritance of the four alleles. Comparative population data suggest that red cell PGM typing by isoelectric focusing might prove to be a useful genetic marker in anthropological studies.
Blood samples from 1109 individuals, residents of two villages in The Gambia, West Africa, have been examined for red cell G6PD. Using both starch gel electrophoresis and a spectrophotometric assay, preliminary phenotypes were assigned to the 519 males and 590 females. The G6PD genotypes were established by reference to the family trees of the two village populations. In addition to the G6PD alleles B+, A+ and A-, a fourth allele, representing a new variant of human G6PD was discovered between the two villages, despite their being of the same tribal origin and only five miles apart.
During the course of a large survey of red cell G6PD genotypes in The Gambia, a slow electrophoretic variant with reduced enzyme activity was found to occur at a high frequency. This variant, G6PD Gambia, was found in the following genotypic combinations: males; G6PDGam, females; G6PDA+/Gam, G6PDB+/Gam, and G6PDA-/Gam. From the electrophoretic mobility and kinetic characteristics it was concluded that G6PD Gambia was a hitherto unreported variant of G6PD. The frequency of the G6PDGam gene amongst the 1109 individuals examined was 0.024.
A rapid method is described for the measurement of total glycosylated haemoglobins (HbA1(a+b+c). The procedure utilizes 0.05 ml of blood and takes forty minutes to complete manually. Eighty blood samples can be analysed without automation by one person in a day. Each analysis uses less than 2 mg of potassium cyanide, resulting in a method that is both safe and rapid for routine hospital laboratories. The inter-assay coefficient of variation was 4% and that for intra-assay measurements 3%, over the range 5-20%, HbA1(a+b+c). The method confirmed that the level of HbA1(a+b+c) is elevated in imperfectly controlled diabetics. Amongst patients with blood glucose levels of less than 10 mmol/l the mean level of HbA1(a+b+c) was found to be 8.5%; samples from 14 known diabetics gave a mean value of 10.9%, whereas 17 known non-diabetic samples gave a mean value of 8.3%. In the group of samples from 27 diabetic individuals with blood glucose levels above 10 mmol/l the mean level of HbA1(a+b+c) was found to be 13.5%.
1. Soluble extracts from different strains of Trypanosoma evansi were compared by several analytical procedures. 2. No isoenzymic differences were detected. 3. Some clear intraspecies differences in protein isoelectric points, in polypeptide sizes and in free amino acid contents were found.
Six hundred individuals of pure Dutch ancestry have been typed for their erythrocyte phosphoglucose isomerase phenotypes by starch gel and cellulose acetate electrophoresis. In two individuals a variant phenotype was discovered. One phenotype was found to be indistinguishable from PGI-Phillips. The other variant would appear to be a new phenotype and has been designated PGI-Jager.
Human erythrocyte glyoxalase I has been subjected to starch gel electrophoresis, and its isoenzymatic forms have been visualized by a new positive staining procedure. The enzyme exhibits polymorphism and holds promise as a useful new genetic marker.
Erythrocytes from 1,168 donors, comprising almost the entire populations of two rural Gambian villages, have been tested for Duffy blood group antigens using antisera to both Fya and Fyb. All tests were negative. Blood film examination of the same samples showed complete absence of Plasmodium vivax parasitaemia, but infections with P. falciparum,P. malariae and P. ovale were observed. The findings are consistent with the view that the Duffy-negative phenotype, FyFy, constitutes the basis of innate resistance towards infection with P. vivax but not towards infection with the other plasmodial species.
A survey of blood samples from the inhabitants of the Shetland Islands has revealed the presence of a variant haemoglobin in 1 individual out of the 345 tested. The rariant haemoglobin accounted for 46% of the total haemoglobin. Tryptic digestion and amino acid analysis indicated that the variant haemoglobin was caused by the substitution of a glutamic acid residue at position 22 in the beta chain by a lysine residue. This is the same amino acid substituion as found in haemoglobin E Saskatoon.