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H Harris

Publications and source records attributed to H Harris.

At least 235 records · Page 13Linked to original sources
PubMed1976

Human enolase isozymes: electrophoretic and biochemical evidence for three loci.

1. Four major enolase isozymes have been identified in human tissues and are referred to as L, M, 'intermediate' and 'fast'. The M isozyme is the major form found in skeletal muscle and heart extracts and the L isozyme the major form found in extracts of liver and most other tissues. The 'intermediate' and 'fast' isozymes are most active in brain but are observed as weak components in most other tissues including heart but are not seen in skeletal muscle. It was observed that during fetal development of heart and skeletal muscle the L form declines in activity while the M form increases in activity. 2. The kinetic properties, heat stabilities and molecular sizes of the main enolase isozymes have been compared. Although the isozymes share many features in common, the 'fast' isozyme is more stable when subjected to heat treatment than either the L or M isozymes. Further, the 'fast' isozyme retains its dimeric structure and activity in the absence of magnesium ions while the L and M isozymes dissociate and lose activity. The 'intermediate' isozyme has properties which are intermediate to those of the L and 'fast' isozymes. 3. The 'intermediate' isozyme can be partially dissociated to equal quantities of L and 'fast' isozymes by storage at room temperature or by freezing and thawing in the presence of 2 M-NaCl. Conversely, mixtures of L with 'fast' and M with 'fast' give rise to an 'intermediate' isozyme after freezing and thawing. 4. Evidence derived from this study has led to the suggestion that three separate gene loci are involved in the determination of human enolase. It is proposed that one of these, ENO1, determines the L isozyme which is the homodimer alphaalpha; another locus, ENO2, determines the 'fast' isozyme which is the homodiner betabeta; and the third locus, ENO3, determines the M isozyme which is the homodimer gammagamma. The 'intermediate' isozyme seen as a strong component in brain and as a weak component in most other tissues is thought to be the heterodimer alphabeta. In heart however it is probably mainly betagamma.

Brain↗
PubMed1976

Adenylate kinases in man: evidence for a third locus.

The tissue distribution of the adenylate kinase isozymes in man has been examined using various substrates. The isozymes attributable to the AK1 and AK2 loci were identified, and an additional set of isozymes probably attributable to a third locus was also found. This locus has been provisionally designated AK3. The AK3 isozymes show activity with either GTP + AMP or ITP + AMP but do not show activity with ATP + AMP. They also differ from the AK1 and AK2 isozymes in electrophoretic mobility and from the AK1 isozymes in being resistant to silver inhibition. They are similar in molecular size to the AK1 isozymes whereas the AK2 isozymes are apparently larger. The AK3 isozymes evidently correspond to the enzyme nucleosidetriphosphate-adenylate kinase (2.7.4.10). Somatic cell hybrid studies indicate that the AK3 locus is not syntenic with that of AK2 (chromosome 1). The AK3 locus is however, probably syntenic with the AK1 locus, on chromosome 9. Genetically determined variation of AK3 has not been seen in a survey of about 80 individuals.

Adenosine Monophosphate↗
PubMed1976

The distributions of subunit numbers and subunit sizes of enzymes: a study of the products of 100 human gene loci.

1. A tabulation of subunit numbers and subunit sizes of a series of enzymes which have been studied electrophoretically in man is presented. The series of subunit numbers cover the isozyme products of 100 distinct gene loci. For 99 of these, estimates of subunit size are given. 2. The distribution of subunit numbers in the whole series is as follows: monomers, 28; dimers, 43; trimers, 4; tetramers, 24; octamers, 1. 3. The subunit sizes range from 13,000 to 116,000. The average subunit size for the whole series is close to 45,800. This corresponds to an average polypeptide chain length of about 425 amino acids. 4. No significant differences were found between the average subunit sizes for the separate classes of enzyme with different subunit numbers. 5. The enzymes were categorized in six different types according to the classification of the International Enzyme Commission. It was found that the oxido-reductases differed from the other types (transferases, hydrolases, lyases, isomerases, ligases) in showing a much greater proportion of multimeric enzymes. Only 1 out of 24 oxido-reductases appeared to be a monomer, whereas in the other enzyme types approximately one-third of the enzymes considered appeared to be monomers. No significant differences in subunit size were found between the various enzyme types. 6. It was found that, in general, where two or more separate gene loci are concerned in determining sets of isozymes with the same or very similar enzyme characteristics, there is a close correlation in subunit size and in most, though not all, cases the subunit numbers are the same.

Chromosome Mapping↗
PubMed1976

Characterization and tissue distribution of N-acetyl hexosaminidase C: suggestive evidence for a separate hexosaminidase locus.

1. An electrophoretic system in which N-acetyl hexosaminidase C (HEX(C)) MIGRATES LESS ANODALLY THAN N-acetyl hexosaminidase A (HEX(A)) is described. 2. HEX(C) is shown to differ from HEX(A) and HEX(B) in substrate specificity, molecular size and affinity for Concanavalin-A. 3. HEX(C) is present in a wide range of adult and foetal tissues and in tissues from patients with Tay-Sachs and Sandhoff's diseases. It is particularly prominent in brain, testis, thymus and lymphoblastoid cell extracts and in several foetal tissues. 4. It is suggested that HEX(C) is coded at a separate gene locus from HEX(A) and HEX(B).

Acetylglucosaminidase↗
PubMed1976

Isozymes of glyceraldehyde-3-phosphate dehydrogenase in man and other mammals.

Multiple electrophoretically distinct forms of glyceraldehyde-3-phosphate dehydrogenase have been observed in human and other mammalian tissues. The human isozymes appear to have essentially the same structural and kinetic properties. An apparent correlation between red-cell age and the relative intensities of the isozymes supports the idea that the isozymes arise as a result of post-translational modification of the polypeptide chain. The possibility that a second locus is involved in the determination of these isozymes is discussed.

Adult↗
PubMed1976

Nasal continuous positive airway pressure. Improvement in arterial oxygenation in hyaline membrane disease.

Continuous positive airway pressure (CPAP) was employed using nasal prongs in 30 neonates with hyaline membrane disease (HMD). There was a significant improvement in mean PaO2 (from 47 to 80 mmHg;p less than 0.001) with no significant change in PaCO2 or pH within a mean 36 min of therapy. Use of the technique allowed reduction of FiO2 to less than 0.60 in less than 20 h in 18 infants. Infants treated within 24 h of birth had significantly greater improvements in PaO2. Complications were infrequent and only 3 of 30 babies developed a pneumothorax while on nasal CPAP. Only 1 of the 23 survivors required mechanical ventilation in addition to nasal CPAP.

Carbon Dioxide↗
PubMed1976

Synthesis of a liver enzyme in hybrid cells.

Rat hepatoma cells were fused with cells of an established mouse lymphoma line, with normal diploid mouse macrophages, lymphocytes and fibroblasts and with normal diploid rat macrophages and lymphocytes. The liver-specific enzyme tyrosine aminotransferase was produced by almost all the hybrid cells, but usually at a lower level than in the parental hepatoma cells. Most of the hybrids also showed increased levels of this enzyme after exposure to dexamethasone. In the rat x mouse hybrids, the electrophoretic mobility of the enzyme indicated that only the rat hepatoma enzyme was produced. The findings are difficult to explain in terms of simple models involving a single diffusible repressor or activator of tyrosine aminotransferase synthesis.

Cell Line↗
PubMed1976

Endotracheal intubation and its relationship to bacterial colonization and systemic infection of newborn infants.

The role of antibiotics in preventing respiratory tract bacterial colonization and systemic infection after orotracheal intubation was prospectively studied in 54 newborn infants. Respiratory tract colonization was assessed from nasopharyngeal and tracheal aspirate cultures obtained at intubation and daily thereafter, while systemic infection was monitored by blood, cerebrospinal fluid, and suprapubic urine cultures performed initially and every three days thereafter while intubated. Colonization and systemic cultures were also obtained at extubation or death. The study group, provided with antibiotics at intubation, and the control group were similar in birthweight and gestational age, as well as race, sex, hospital or origin, and indication for intubation. Colonization at intubation was five times more common in infants intubated 12 or more hours after birth than in infants intubated earlier. Subsequent colonization was twice as frequent in infants intubated longer than 72 hours as well as in those requiring two or more reintubations. Systemic infection occurred only in those infants who were initially or subsequently colonized and was three times more frequent in the control group than in the study group.

Anti-Bacterial Agents↗
PubMed1975

An examination of the age-related patterns of decay of the hexokinases of human red cells.

A previous method for red cell fractionation by density gradient centrifugation, using a swing-out rotor, has been scaled up to deal with larger volumes of red cells. This method, involving the use of a zonal rotor, is described and has been applied to the study of the decay of hexokinase in the red cells of normal individuals. Hexokinase activity was seen to fall very rapidly in the young cells followed by a much more gradual decline in older cells. It is estimated that the mature red cell probably contains no more than 2-3% of the hexokinase activity originally present in the reticulocyte. An electrophoretic study showed a changing pattern of the isozymes HK1 and HK2 with increasing cell age. HK2 declines very rapidly in the early fractions whereas HK1 appears to decay more gradually.

Erythrocyte Aging↗
PubMed1975

An investigation of some factors affecting levels of erythrocyte inorganic pyrophosphatase activity.

A reproducible method has been devised for assaying erythrocyte inorganic pyrophosphatase. The activity level in healthy individuals appears to be a constant characteristic. Population surveys have been carried out in 100 Europeans and 34 Indians. In each population an otherwise normal individual was found with activity approximately three standard deviations from the mean. Investigation of the family of one such individual indicated that this was an inherited characteristic. A few individuals with clinical abnormalities were examined and some were found to have activity levels above the normal range. High activity levels appeared to be associated with those diseases in which raised circulating reticulocyte levels are found. The rate of in vivo decay of erythrocyte inorganice pyrophosphatase has been measured in healthy individuals. The decay pattern appears to be of the constant logarithmic type. An estimate has been made of the activity in circulating reticulocytes, and the half life of the enzymes has been calculated.

Adolescent↗
PubMed1975

Genetic determinants of morphological differentiation in a lymphoma-sarcoma hybrid.

Hybrid cells, YACIR/MSWBS were produced by fusion of the cells of a methylcholanthrene induced murine sarcoma MSWBS and a virus induced murine lymphoma YACIR. The hybrid cells were maintained in vitro and syngenic mice challenged at various periods after fusion. Karyological analysis has been performed on the cell line, and on the tumours which arose in vivo. The tumours were also examined histologically. Over the 2 yr following fusion there was a progressive loss of chromosomes but biarmed MSWBS derived chromosomes were selectively retained. Tumours could be divided into those whith a chromosome complement similar to that of the early line in vitro, those in which chromosome loss had occurred and those in which karyology showed a mixture of the two foregoing types. Histology showed a minority of sarcoma-like tumours reminiscent of MSWBS and the majority of these showed little chromsome loss. Most tumours showed an intermediate morphology and the great majority of these had lost moderate numbers of chromosomes. There was a very small number of lymphomatoid tumours in which chromosome loss was marked.

Animals↗
PubMed1975

An electrophoretic study of the distribution and properties of human hexokinases.

An electrophoretic system which gives a clear separation of human hexokinases HK1, HK2 and HK3 is described. The distribution of the hexokinase isozymes in various human tissues, both adult and fetal, is reported. Some properties of the isozymes were investigated. HK2 was found to be more thermolabile than HK1, and there was also a small but significant difference in molecular size. Unlike HK3, HK1 and HK2 are not inhibited by high glucose concentrations. Screening of red cell lysates from 800 unrelated European individuals revealed no genetic variants of HK1 and HK2. However, in view of their difference in properties, it seems probable that the HK1 and HK2 isozymes are determined by separate gene loci.

Brain↗
PubMed1975

Genetic studies on human lymphoblastoid cell lines: isozyme and cytogenetic heterogeneity in a cell line, with evidence for localization of the Pep A locus in man.

One hundred and thirty-three clones (60 mutagen treated, 73 controls) of the human male lymphoblastoid cell line F 137 have been examined for the electrophoretic pattern of more than 30 enzymes. In nine instances there was loss of activity of one allele of an X-linked or heterozygous autosomal locus. Seven of these involved the Pep A locus, and in every case the change was from the Pep A 2-1 phenotype to Pep A 2. Cytogenetic analysis of the parent line revealed a number of variants on the modal karyotype. On cloning, there appeared to be some selection for survival of non-modal cells. The proportions of the cytogenetically distinct populations within the bulk culture varied over a period of many months. There was a strong correlation in individual clones between loss of activity of the product of the Pep A1 allele and the presence in the cells of a 9/18 translocation. In addition there was one clone of phenotype Pep A 2 with a deletion of part of the long arm of chromosome 18. The data confirms the assignment of the Pep A structural locus to the distal half of the long arm of chromosome 18 and localizes it with some precision to the qter region. The Pep A 2 phenotype of the clones containing the 9/18 translocation could be the result of a small deletion eliminating the Pep A1 allele but not large enough to be detected cytogenetically. Alternatively inactivation of the Pep A1 allele may have occurred as a position effect resulting from the close association of heterochromatin from the centromere of 9 with the qter region of 18.

Cell Line↗
PubMed1975

Aconitase polymorphism in man.

1. An electrophoretic method is described which resolves two groups of aconitase isozymes in human tissues, one group corresponding to the mitochondrial and the other to the soluble enzyme. This method has been used to screen human populations for electrophoretic variation. 2. Variant phenotypes of both the mitochondrial and the soluble aconitase are described, and family studies and sib-pair data demonstrate that the variation is genetically determined. 3. The variant isozyme patterns are accounted for in terms of allelic variation at two independent gene loci, ACONM and ACONS, which encode the mitochondrial and the soluble aconitase respectively. The electrophoretic survey has so far revealed two alleles at ACONM and seven alleles at ACONS. 4. The electrophoretic patterns shown by heterozygous individuals indicate that both soluble and mitochondrial aconitase are monomeric. The variant patterns also indicate that certain minor aconitase components resolved under the electrophoretic conditions employed represent 'secondary' isozymes of the primary translation products. 5. Population data on Europenas and Nigerians are presented and it is shown that both rare and common electrophoretic variants are segregating in the human species. The variation due to the three most common ACONS alleles in the Nigerians constitues a polymorphism.

Aconitate Hydratase↗