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Biomedical subjects

H Harris

Publications and source records attributed to H Harris.

At least 217 records · Page 12Linked to original sources

Polymorphism and the subunit structure of enzymes: a contribution to the neutralist-selectionist controversy.

The occurrence of polymorphism in a series of 87 different loci coding for enzyme structure in human populations has been related to the size and the number of subunits in the corresponding enzymes. Polymorphic and nonpolymorphic enzymes did not differ on average in subunit size. However, multimeric enzymes showed a significantly lower incidence of polymorphism than didmonomeric enzymes. A particularly low incidence of polymorphism was noted among multimeric enzymes in which interlocus molecular hybrids occur. The findings are discussed in terms of the "neutralist" and "selectionist" hypotheses of polymorphism.

Enzymes↗

The distribution of subunit sizes of soluble proteins in human tissues.

1. The distribution of subunit sizes of soluble proteins in human tissues has been examined by the technique of gel filtration chromatography followed by SDS polyacrylamide gel electrophoresis. 2. Up to 101 different polypeptides were identified. These appear to represent primarily the substituent polypeptides of easily solubilized 'non-enzyme' proteins. 3. The subunit sizes ranged between 7000 and 270000 and the distribution was continuous unimodal and skewed. The mean size was estimated at 54 600+/-42 900. 4. The distribution of subunit sizes and the overall mean were found to be similar to those reported for easily solubilized human enzymes and other vertebrate proteins. These results suggest that the average structural gene coding such polypeptides consists of about 1400 base pairs.

Electrophoresis, Disc↗

Lysosomal enzymes in human lymphoblastoid lines: unusual characteristics of RAJI and DAUDI.

The lysosomal enzymes N-acetyl hexosaminidase, alpha-galactosidase and alpha-mannosidase vary in electrophoretic mobility in different human lymphoblastoid (lymphoid) lines. The relative mobilities of these three enzymes and three out of four other lysosomal enzymes tested correlate well with each other. The patterns appear to be relatively stable characteristics of each line. The lines RAJI and DAUDI show a strikingly fast electrophoretic mobility for all of these enzymes. N-acetyl hexosaminidase is also markedly deficient in DAUDI.

Cell Line↗

The deficiency of a lysosomal acid hydrolase in two clones derived from the human lymphoblastoid line F137 after mutagen treatment.

Two clones (out of a total of 181 clones tested) derived from the human lymphoblastoid (lymphoid) line F137 after mutagen treatment were found to be deficient in a lysosomal acid hydrolase. The clone N32 derived from EMS-treated F137 is deficient in N-acetyl hexosaminidase A and B but contains normal levels of N-acetyl hexosaminidase C and low levels of an enzyme resembling N-acetyl hexosaminidase S. Thus the enzyme deficiency in this clone appears to resemble the so-called Sandhoff variant of Tay-Sachs disease, a disease inherited as an autosomal recessive condition. The clone G3 derived from MNNG treated F137 is deficient in alpha-galactosidase A. This clone resembles the situation in X-linked Fabry's disease. Karyotype analysis of the clones failed to reveal any chromosome rearrangement or losses of chromosomal material that might have accounted for the mutations and it is suggested that a single point mutation might in each case account for the loss of enzyme activity. No storage of the natural substrates of the two enzymes could be demonstrated in the clones.

Cell Line↗

The distribution of isoelectric points of human soluble proteins and in particular of the enzyme products of 88 human gene loci.

The isoelectric points of the 'primary' isozymes coded for by 88 human gene loci have been determined. The distribution was found to be bimodal with an antimode at the 'physiological pH'. Soluble human proteins have the same distribution and this appears to be characteristic of soluble mammalian proteins in general. There may be some correlation with function, mitochondrial enzymes being more basic and hydrolytic enzymes being more acidic than other classes of enzymes. The bimodal distribution can be explained in terms of the buffering effects of the charged amino acids. Most proteins would thus appear to be charged at neutral pH values.

Alleles↗

Architectural design: the spatial location and interactions of old people.

Residents' interactions in the sitting spaces of purpose-built Homes for old people were studied by participant and structural observation. Eight Homes were sampled from a larger number to represent factors of size (large and small), design (institutional and family) and mental designation of residents (confused or rational). Verbal exchanges between residents were analysed in terms of initiators' and respondents' mental designations. The residents' locations within the sitting spaces and in the sleeping and dining areas of the Homes were recorded. Examination of these data suggests that residents of different mental designations are segregated from each other. Some architectural design elements of physical settings that might foster integration are outlined.

Aged↗

The analysis of malignancy by cell fusion. VIII. Evidence for the intervention of an extra-chromosomal element.

Diploid human fibroblasts and lymphocytes were fused with the cells of a malignant mouse melanoma and a range of hybrid clones selected for study. The ability of these clones to produce progressive tumours was assayed in nude mice. Although human chromosomes were preferentially eliminated in all the hybrid clones, the human diploid cells were as effective as mouse diploid cells in suppressing the malignancy of the mouse melanoma cells. The suppression produced by fibroblasts was again more profound than that produced by lymphocytes. Malignancy was also found to be suppressed in a hybrid clone in which a single X was the only human chromosome present; and this clone continued to give a very low take incidence even after the human X had been eliminated by back selection. Hybrids were made between the melanoma cells and diploid human fibroblasts that had been given 100 J kg-1 of gamma radiation before cell fusion. These hybrids contained no recognizable human chromosomes, but their ability to produce progressive tumours was greatly reduced compared to that of the melanoma parent cells. The take incidences given by the crosses between the melanoma cells and the irradiated human fibroblasts were, however, substantially higher than those given by the crosses between the melanoma cells and unirradiated fibroblasts. These findings suggest that the suppression of malignancy involves the activity of some extra-chromosomal element and that this element is radio-sensitive.

Animals↗

Gene transfer by means of cell fusion I. Statistical mapping of the human X-chromosome by analysis of radiation-induced gene segregation.

Hybrid cells were obtained by virus-induced fusion of hamster cells with irradiated human cells. The analysis of such hybrids permits a study of the effects of lethal doses of radiation on human cells and provides a method of sub-chromosomal genetic mapping that is independent of karyological analysis. Radiation-induced chromosome exchanges are shown to be extremely localized, and a map of 4 X-linked genes is presented.

Animals↗

Gene transfer by means of cell fusion. II. The mapping of 8 loci on human chromosome 1 by statistical analysis of gene assortment in somatic cell hybrids.

A method is described which should permit determination of the order and spacing of genes on all human chromosomes by the analysis of just one set of man-mouse hybrid cells. This method is used to determine the map of 8 loci on human chromosome I. A comparison of the statistical maps of chromosome I and of the X-chromosome with the cytogenetic maps of these chromosomes at metaphase indicates that the statistically derived distances between genes are related to the amount of Giemsa light-band material between the genes.

Animals↗

Growth in vitro of tumour cell x fibroblast hybrids in which malignancy is suppressed.

We have studied the growth in vitro of a lymphoma x fibroblast hybrid and several melanoma x fibroblast hybrids in which malignancy is suppressed. The parental cells, the hybrids, and malignant segregants derived from the hybrids were analysed for serum requirement, cloning efficiency in soft agarose, density-dependent inhibition of growth, and secretion of plasminogen-activating enzyme. One malignant segregant from the lymphoma x fibroblast cross was found by a number of criteria to have a more highly 'transformed' phenotype than the hybrid from which it was derived. However, in the case of the melanoma x fibroblast crosses, none of the parameters examined could be correlated in a direct way with malignancy.

Clone Cells↗

Pulmonary pseudocysts in the newborn infant.

Five neonates who developed a pulmonary pseudocyst are reported. All infants had clinical hyaline membrane disease and were treated with continuous distending airway pressure. The pseudocysts developed between 39 hours and 7 days of age. In all but one pulmonary interstitial emphysema preceded or occurred together with the development of the pseudocyst. All babies went on to complete clinical recovery without surgical intervention. Radiologic documentation of the spontaneous resolution of the pseudocyst was obtained in three infants and occurred over three days, five days, and three months, respectively.

Cysts↗

Tumorgenicity of L cell derivatives and hybrid cells derived from them.

Hybridization studies on high and low malignant L cell derivatives support our previous conclusions, in showing that crosses between highly tumorigenic and poorly tumorigenic lines to a marked suppression of the malignant phenotype. Malignant behaviour is not, however, suppressed when cells from one highly tumorigenic line are crossed with those of another tumorigenic line. The present results show further that these rules apply even when all the cells crossed are closely related derivatives of one cell line.

Animals↗