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Biomedical subjects

G K Scott

Publications and source records attributed to G K Scott.

At least 73 records · Page 4Linked to original sources
PubMed1986

Does a fibroblast membrane proteinase affect the binding, uptake and metabolism of epidermal growth factor?

Pre-treatment of human fibroblasts to inhibit a cell-surface growth-related proteinase inhibits the mitogenic action of epidermal growth factor. It also reduces the binding of epidermal growth factor to these cells, and lowers the rate of internalisation and degradation of the growth factor, but quantitative considerations render it unlikely that these parameters contribute directly to the inhibition of mitogenesis.

Biological Transport↗
PubMed1985

The gene for rat atrial natriuretic factor.

Atrial natriuretic factor (ANF), a peptide hormone recently isolated from heart atria, appears to play an important role in the regulation of extracellular fluid volume and blood pressure. Indeed, natural and synthetic ANF rapidly and markedly stimulate natriuresis and diuresis and produce smooth muscle relaxation. Consistent with the hypothesis that ANF is a novel hormone, it was recently shown that ANF is present in circulation, and high affinity membrane receptors specific for ANF have been described in renal, vascular, and adrenal tissues. These important biological activities suggest that conditions like hypertension could be associated with defective ANF gene expression. We and others have shown by cDNA cloning that ANF is part of a larger precursor, pro-natriodilatin (PND). We now describe the isolation and structural analysis of the rat PND gene. Southern blot analysis of rat genomic DNA suggests the presence of a single PND gene per haploid genome. The PND coding sequences are interrupted by two short introns. A long alternating purine-pyrimidine tract (GT)9GATG(GT)27 is found 111 base pairs downstream of the polyadenylation site; such sequences could adopt Z-DNA configuration and they have been associated with sequences that appear very active in intergenic recombination. Comparison of the rat and human PND genomic sequences shows highest homology in 5'-flanking as well as in coding sequences. The rat PND gene will be a useful model to study the physiology and pathology of this important regulator of the cardiovascular system.

Animals↗
PubMed1985

Further evidence for a cell surface proteinase essential to the growth of cultured fibroblasts.

Specific antibodies and protein proteinase inhibitors will inhibit cell-surface proteinase activity on human fibroblasts and cause a concomitant inhibition of DNA synthesis and of cell multiplication. An insolubilized proteinase inhibitor also inhibits cell multiplication. The same reagents partially inhibit the multiplication of mouse L cells, both in monolayer and suspension culture, and inhibit the mitogenic effect of epidermal growth factor (EGF) on both types of cell.

Animals↗
PubMed1985

Antifreeze protein genes are tandemly linked and clustered in the genome of the winter flounder.

We have used genomic Southern blots and restriction maps of genomic clones to examine the organization of the antifreeze protein multigene family in the winter flounder. The majority of the approximately equal to 40 antifreeze protein (AFP) genes in this fish are present in 7- to 8-kilobase-pair (kbp) elements of DNA, which are iterated as tandem direct repeats. Each repeat contains a single antifreeze protein gene that is 1 kbp long, and all of these genes have the same transcriptional orientation. Although the repeated elements are highly homologous, they do show some restriction site and restriction length polymorphisms. When flounder genomic DNA is digested with restriction endonucleases that do not cut within the repeats, most of the antifreeze protein genes reside in fragments that are at least 40 kbp long, representing clusters of five or more repeats in tandem. After genomic DNA is digested with Xba I or Xho I, these genes are present in fragments of exceptionally high molecular weight, suggesting that the clusters themselves are grouped together in the genome. The AFP gene locus may have evolved by gene amplification as recently as 10(6) years ago in response to the onset of the Cenozoic ice age.

Animals↗
PubMed1984

Antifreeze protein genes of the winter flounder.

A genomic library of the winter flounder in lambda phage Charon 4 was screened with antifreeze protein cDNA. Nine genomic clones were isolated from three haploid genome equivalents of phage and were grouped into three classes on the basis of restriction mapping and heteroduplex analysis. The three chromosomal regions are non-overlapping and each contain two antifreeze protein genes spaced from 3 to 7 kilobase pairs apart. Genomic Southern blots indicate that these six non-allelic genes represent only 10-20% of the complement of this large multigene family. One gene has been identified by sequencing as a variant of the gene encoding the most abundant antifreeze protein. This gene is 1.0 kilobase pair long and contains an intervening sequence of 0.6 kilobase pairs between the coding region for the bulk of the signal sequence and that coding for the proprotein.

Amino Acid Sequence↗
PubMed1984

Mitogenic proteinases from human leukocytes.

Serine proteinase activity has been identified in purified human lymphocyte membranes, and the corresponding enzymes have been isolated from human leukocyte extracts by affinity chromatography. The localization of these enzymes on lymphocyte and granulocyte membranes has been immunochemically demonstrated. Mitogenic activity towards human lymphocytes has been demonstrated for these enzymes, and anti proteinase antibodies inhibit the growth of transformed lymphocytes. The proteinases are similar in many properties to enzymes previously isolated from human leukocytes, and reported to be involved in a wide variety of leukocyte functions.

Cell Division↗
PubMed1984

Membrane proteinases from normal and neoplastic tissues in man and the rat.

Plasma membranes were purified from rat liver, muscle and sarcoma tissues and from human liver and hepatoma tissues. The plasma membranes all contained DFP-sensitive, neutral proteolytic activity. Plasma membranes from all normal tissues contained a single DFP-binding protein of apparent molecular weight 68,000. Only the plasma membranes from tumour tissue contained a plasminogen activator; the DFP-binding proteins from these membranes were more diverse than those from the normal samples. The rat liver plasma membrane proteinase was purified. It was a labile enzyme sensitive to inhibition by DFP and by calcium ions, and with a broad substrate specificity. A similar protein was the sole DFP-binding protein in rat liver microsomes. This and the properties of the enzyme suggested a possible role in the processing and secretion of newly-synthesized protein.

Animals↗
PubMed1984

Antibody affinity chromatography of human proteinases and related proteins.

Antibodies specific for a purified proteinase from the cell-surface of human leukocytes were used to prepare an antibody affinity chromatography column. This column bound a variety of proteins from extracts of human cells and tissues and from human body fluids, indicating that proteins immunologically related to the leukocyte proteinase are widespread in the human body. For human urine and a human fibroblast extract, a single protein species with serine proteinase activity was eluted from the column in each case. Small quantities of a heterogeneous protein fraction were also weakly bound to the column from an extract of mouse submaxillary glands.

Antibodies↗
PubMed1983

Disturbance of lysosomal glycogen metabolism by liposomal anti-alpha-glucosidase and some anti-inflammatory drugs.

The size-distribution of liver glycogen was shown to be distinctly affected by the anti-inflammatory drugs salicylate and indomethacin. By measurement of the incorporation of radioactive glucose into glycogen, salicylate was shown to have a depressing effect on overall liver glycogen metabolism. These effects appear to arise from the stabilizing of the lysosome by the drugs. The incorporation, via liposomes, of purified anti-1,4-alpha-glucosidase activity and in the content of high-molecular-weight glycogen. These changes are increased by prolonged liposomal antibody treatment and suggest that a possible feedback control mechanism operates in the incorporation of glycogen into lysosomes. These experiments may be useful as a model of glycogen turnover and its failure in glycogenosis type II (Pompe's disease).

Acarbose↗
PubMed1982

Neutral proteinases from human blood cells.

1. Human erythrocytes essentially essentially uncontaminated by leukocytes retain considerable proteolytic activity in the membrane fraction. 2. The enzyme responsible has similar properties to previously-reported human erythrocyte membrane proteinases. 3. A particulate fraction from human leukocytes does not yield a similar enzyme when extracted and fractionated in the same way.

Chromatography, Gel↗
PubMed1981

Human serum complement requirements for bacterial killing and protoplast lysis of Escherichia coli ML308 225.

Normal human serum kills Escherichia coli ML308 225 and lyses protoplasts derived from this organism. Human serum which is depleted of complement component C9 or deficient in component C8 is not bactericidal, but C9-depleted serum will lyse protoplasts whereas C8-deficient serum will not. Bacterial lipopolysaccharide, which can protect bacteria from the serum bactericidal reaction, does not protect protoplasts from lysis by serum.

Bacteriolysis↗