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Biomedical subjects

H Harris

Publications and source records attributed to H Harris.

At least 253 records · Page 14Linked to original sources

Sub-unit structure of soluble and mitochondrial malic enzyme: demonstration of human mitochondrial enzyme in human-mouse hybrids.

1. Malic enzyme has been examined by starch-gel electrophoresis in human cultured fibroblasts and in 60 brain samples. The polymorphism of MEM has been confirmed and the electrophoretic pattern suggests that this enzyme, like MES, is a tetramer. 2. The appearance of the soluble and mitochondrial malic enzymes in mouse and Chinese hamster is described, and the identity of the enzymes in man, mouse and hamster has been established from a study of interspecific somatic cell hybrids. In man and in hamster MES migrates anodal to MEM, whereas in the mouse MES is relatively less anodal than MEM. 3. Segregation of human enzymes in human--mouse and human--hamster somatic cell hybrids confirms the synteny of MES and PGM3. Data from human--mouse hybrids suggest that MEM is probably not syntenic with MES is probably not syntenic with MES in man, nor is it syntenic with GPI.

Animals↗

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↗

Genetically determined polymorphism of a form of hexokinase, HK III, found in human leucocytes.

1. A form of hexokinase which appears to correspond to HK III, seen in liver, spleen and lung, has been identified in human polymorphonuclear leucocytes. HK III activity has not been demonstrated in lymphocytes, permanent lymphoblastoid cell lines or in cultured fibroblasts. 2. In fresh leucocyte preparations HK III usually appeared as a single band, but in extracts of post-mortem tissues multibanded patterns were seen. Leucocyte preparations also give multi-banded patterns after storage for more than a few hours. 3. In certain individuals the HK III showed a two-banded pattern even in fresh preparations. Repeat samples and family studies suggested that this pattern was genetically determined and represented a heterozygote for a common allele HK1III and a less common variant HK2III. Out of a total of 330 English people successfully tested 10 probable heterozygotes were found. 4. It is suggested that HK III may be a monomeric enzyme whose genetic determination is independent of that of the other main forms of hexokinase.

Alleles↗

Studies on the properties and tissue distribution of the isozymes of guanylate kinase in man.

The isozyme patterns of guanylate kinase were examined in fetal and adult tissues, in cultured cells and also in red cells separated by density gradient fractionation. Results from fetal and cultured cells inidcated that there are three primary isozymes a, c, and e among the seven isozymes of guanylate kinase in man. Serial secondary isozyme production in red cells in vivo showed that isozyme a produces b, c produces d, and e produces f and g. The three sets of isozymes were found to differ in the following properties: activation/inhibition by EDTA; thermostability, and molecular weights. Isoelectric points of several of the isozymes were estimated by isoelectric focusing. It was concluded that the isozymes of guanylate kinase are determined by three separate gene loci.

Brain↗

Affinity chromatography of DNA-binding proteins from human, murine and man-mouse hybrid cell lines.

About 60 proteins from human and murine cell lines were isolated by their ability to bind to different preparations of DNA. In the intact cell, the majority of these proteins are to be found in the cell nucleus. The electrophoretic mobilities of the DNA-binding proteins from human, murine and man-mouse hybrid cell lines were compared in two-dimensional acrylamide gels. Few, if any, species-specific differences were found. These observations suggest that the structures of the vast majority of the proteins that interact with DNA are conserved through evolution. A molecular basis is thus provided for the intracellular of hybrid cells derived from different animal species.

Animals↗

Haemoglobin synthesis in fused cells.

When primitive erythroid cells from 5-day-old chick embryos are exposed to inactivated Sendai virus they do not undergo haemolysis but fuse with other cells by the normal process of cytoplasmic coalescence. In this way cells actively engaged in the synthesis of haemoglobin may be fused with others that are not. In heterokaryons formed by the fusion of such erythroid cells with cells from established mouse or hamster lines, haemoglobin synthesis initially continues at a high level, but then declines and ceases altogether within a period of about 60 h. This decline affects the synthesis of both haem and globin and reflects the activity of specific regulatory mechanism, for under these conditions other chick proteins continue to be synthesized. The haemoglobin synthesized in the heterokaryons is entirely chick, and not mouse or hamster, haemoglobin.

Animals↗

Lack of correlation between malignancy and sensitivity to killing by concanavalin A.

Eight mouse cell lines and seven hybrid clones, both malignant and nonmalignant, were tested for possible correlations between malignancy and sensitivity to killing by concanavalin A (Con A). These cells included six highly malignant and two less malignant cell lines, two malignant and three nonmalignant hybrid clones derived from five different crosses, and two malignant hybrid clones segregated from a cross between malignant and nonmalignant cells. The malignancy of the cells was determined by their ability to grow progressively in irradiated, syngeneic newborn mice and to kill the host. All these cells, except one, showed similar sensitivities to killing by Con A. No correlation could be established between the malignancy of a cell line or of a hybrid clone and its sensitivity to the lectin.

Animals↗