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D M Swallow

Publications and source records attributed to D M Swallow.

99 records · Page 6Linked to original sources
PubMed1975

Acid alpha-glucosidase: a new polymorphism in man demonstrable by 'affinity' electrophoresis.

1. A new polymorphism of the enzyme acid alpha-glucosidase is described. The three phenotypes, 1, 2-1 and 2, appear to be determined by two alleles alpha-GLU1 and alpha-GLU2 at an autosomal locus. The allele frequencies in Europeans are approximately alpha-GLU1 = 0-97 and alpha-GLU2 = 0-03. 2. The polymorphism is not detectable after electrophoresis on other support media (cellogel and agarose) and evidence is presented that the separation is effected by a difference in binding of the isozyme products of the two alleles to the support medium starch, which contains alpha-1-4 and alpha-1-6 linked glucose units. We have called this type of separation affinity electrophoresis. 3. No difference in the kinetic properties of the two enzymes could be demonstrated using 4-methyl umbelliferyl alpha-D-glucopyranoside and maltose as substrates or maltose and turanose as inhibitors, but it is possible that differences might exist when macromolecular substrates are used. 4. One individual with the rare homozygous genotype has been found. There is at present no indication that this genotype is associated with a pathological condition.

Alleles↗
PubMedDate not supplied

The human tumour-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM.

A single highly-polymorphic autosomal gene locus PUM codes for a family of mucin-type glycoproteins, separable by SDS-gel electrophoresis, which we first identified in human urine. The locus also codes for glycoproteins which are abundant in several other normal epithelial tissues and body fluids, including milk, and in tumours of epithelial origin. These mucin-type glycoproteins seem to be very immunogenic in rodents and, in a search for epithelial specific or tumour-associated antigens, a large number of related antibodies have been isolated which bind to the PUM-coded mucins. Many of the antibodies show a pronounced tumour specificity on immunohistology and are being used widely in cancer diagnosis in vitro and in vivo and even in cancer therapy. To investigate the expression of these antigens in normal and malignant cells complementary DNA coding for the mammary mucin has been isolated. Here we present evidence obtained using this cDNA that the PUM locus is a hypervariable 'minisatellite' region of human DNA similar to those described by several groups, but which is novel in that it is transcribed and translated, and that the same polymorphism is demonstrable in the expressed gene product.

Base Sequence↗
PubMedDate not supplied

Common polymorphism in a highly variable region upstream of the human lactase gene affects DNA-protein interactions.

In most mammals lactase activity declines after weaning when lactose is no longer part of the diet, but in many humans lactase activity persists into adult life. The difference responsible for this phenotypic polymorphism has been shown to be cis-acting to the lactase gene. The causal sequence difference has not been found so far, but a number of polymorphic sites have been found within and near to the lactase gene. We have shown previously that in Europeans there are two polymorphic sites in a small region between 974 bp and 852 bp upstream from the start of transcription, which are detectable by denaturing gradient gel electrophoresis (DGGE). In this study, analysis of individuals from five other population groups by the same DGGE method reveals four new alleles resulting from three additional nucleotide changes within this very small region. Analysis of sequence in four primate species and comparison with the published pig sequence shows that the overall sequence of this highly variable human region is conserved in pigs as well as primates, and that it lies within a 1kb region which has been shown to control lactase downregulation in pigs. Electrophoretic mobility shift assay (EMSA) studies were carried out to determine whether common variation affected protein-DNA binding and several binding activities were found using this technique. A novel two base-pair deletion that is common in most populations tested, but is not present in Europeans, caused no change in binding activity. However, a previously published C to T transition at -958bp dramatically reduced binding activity, although the functional significance of this is not clear.

Adult↗
PubMedDate not supplied

Expression of the hypervariable PUM locus in normal and malignant lung: the tumor-associated epitopes are present but masked in normal tissue.

A single highly polymorphic gene locus PUM codes for a family of mucin-type glycoproteins present in human urine. These glycoproteins can be detected after electrophoresis using a group of monoclonal antibodies which show marked tumour specificity on immunohistology and include the HMFG and Ca antibodies (Swallow et al., 1986, 1987). Here we show by electrophoretic analysis of lung specimens and urine samples from nine individuals, that the PUM locus is expressed both in malignant and in normal lung. In contrast immunohistology of frozen sections of normal lung showed very little staining using the same antibodies, occasional reactive type 2 pneumocytes alone staining, whilst the carcinoma material showed strong staining in each case. However, after formalin fixation much more staining was observed in normal lung, all type 1 and 2 pneumocytes being stained. These observations suggest a difference in accessibility of the epitopes in normal and malignant lung, rather than a difference in expression of the PUM gene.

Antigens, Neoplasm↗
PubMedDate not supplied

The breast tumour-associated epithelial mucins and the peanut lectin binding urinary mucins are coded by a single highly polymorphic gene locus 'PUM'.

A family of mucin-type glycoproteins, present in human urine, is coded by a single highly polymorphic gene locus PUM. We have previously shown that these glycoproteins carry epitopes recognized by a series of monoclonal antibodies, many of which were raised to the human milk-fat globule membrane, and which bind to a wide variety of carcinomas and certain normal epithelia. Here we show that in the normal human mammary gland, and in breast cancers the epitopes are present on the same family of molecules as that found in urine. Thus the genetically determined variation at the PUM locus accounts for much of the electrophoretic heterogeneity of the mucin-type glycoproteins present in breast cancer and serum from breast cancer patients that has been reported previously. Knowledge of this normal inherited polymorphism is essential to the interpretation of possible changes to these molecules in malignancy.

Antigens, Neoplasm↗