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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 667 records · Page 37Linked to original sources

Activation of transglutaminase during embryonic development.

Incorporation of [3H]putrescine into proteins was shown to increase markedly in sea urchin eggs upon fertilization. Emetine, an inhibitor of protein synthesis, had no effect on the rate of protein labeling. However, the reaction could be prevented by the addition of 2-[3-(diallylamino)-propionyl]benzothiophene, a noncompetitive inhibitor of transglutaminase, and also by dansylcadaverine, which is a substrate for transglutaminase. The inert N alpha-dimethyl analogue of dansylcadaverine had no influence. Considering the complexity of the incorporation of the [3H]putrescine tracer in this system, it was deemed essential to prove by rigorous analytical methods that the reaction was, indeed, consistent with a transglutaminase mechanism. gamma-Glutamyl[3H]putrescine could be recovered in 80-90% yield from the proteolytic digest of proteins from the 20-min fertilized cell. Another sign of the in vivo activity of transglutaminase was the isolation of substantial amounts of epsilon-(gamma-glutamyl)lysine from proteins of sea urchin embryo, yielding a frequency value for this cross-link as high as 1 mol/400 000 g of protein in the 32-cell-stage material.

Acyltransferases↗

Surface-active biomaterials.

Since the discovery in 1969 of a man-made surface-active material that would bond to bone, a range of materials with the same ability has been developed. These include glass, glass-ceramic, and ceramic materials which have a range of reaction rates and from which it should be possible to select a surface-active material for a specific application. The available materials and their similarities, differences, and current clinical applications are reviewed.

Animals↗

Detection of epsilon(gamma-glutamyl) lysine.

Detection of epsilon(gamma-glutamyl) lysine crosslinks is not only necessary for establishing the importance of the dipeptide as a post-translational modification of proteins, but provides information as to the importance of the transglutaminase enzyme in a biological system. The crosslink may be detected using both indirect and direct methodology. Indirect methods for its detection include measurement of 'masked lysines' within a protein, detection of polymer formation by gel-electrophoresis and the inhibition of crosslinking by the incorporation of small molecular weight amines into the substrate protein. Direct methods for the detection of epsilon(gamma-glutamyl) lysine require the actual isolation of the dipeptide following its release from the sample protein by exhaustive proteolytic digestion. Separation of the dipeptide from other components of the digest may be achieved by either ion-exchange chromatography or gel filtration and its qualitative identification achieved by techniques such as paper-electrophoresis or thin layer chromatography. Quantitative estimation of epsilon(gamma-glutamyl) lysine normally involves its further separation by ion-exchange chromatography and its post-column detection following derivatisation with ninhydrin. More recent techniques include pre-column derivatisation of the dipeptide with fluorogenic reagents such as sigma-pthalaldehyde and separation by reverse phase HPLC. With the recent advances in liquid chromatography resulting in the improved resolution of amino acids, increased sensitivity, rapid analysis times, and small sample sizes, it appears likely that direct quantitation of epsilon(gamma-glutamyl) lysine will be the preferred method for the future.

Acyltransferases↗

Hemorrhage from congenital renal arteriovenous malformation in pregnancy.

A case report of life-threatening hemorrhage from a congenital renal arteriovenous malformation during pregnancy is presented. The hyperdynamic circulatory state that exists during pregnancy may predispose to bleeding from vascular malformations. We review the classification and clinical presentation of renal arteriovenous malformations.

Adult↗

Pyrido[3',2':4,5]thieno[3,2-d]-N-triazines: a new series of orally active antiallergic agents.

A new series of orally active mediator release inhibitors, pyrido[3',2':4,5]thieno[3,2-d]-N-triazines, was synthesized and evaluated for antiallergic activity. Several products showed high activity as inhibitors or wheal information in the rat passive cutaneous anaphylaxis screen and as inhibitors of histamine release from passively sensitized rat mast cells. Many compounds were orally active in the PCA test. The most potent compound, 7-phenylpyrido-[3',2':4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)- one (10) with an I50 value of 0.05 microM, was 60 times more potent than disodium cromoglycate (DSCG) in the RMC assay.

Administration, Oral↗

Cortical subacute necrotizing encephalomyelopathy. A study of two patients with mitochondrial dysfunction.

Two patients are reported who presented with progressive impairment of neurological and intellectual function, and intractable fits. In both the disease ran a fluctuating course. There was evidence of mitochondrial dysfunction, serum levels of pyruvate and lactate being four to six times normal. Involvement of mitochondria in different organs was suggested by histochemical and ultrastructural investigations of muscle and heart tissue. The children died at nine years and twelve months, respectively. In both autopsy revealed cardiomyopathy and renal abnormalities. The brain showed severe lesions indistinguishable from subacute necrotizing encephalomyelopathy (SNE), the brunt of which was borne by the cortex.

Cerebral Cortex↗

Synthesis of spore proteins during development of Dictyostelium discoideum.

The pattern of synthesis of the spore coat proteins during development of Dictyostelium discoideum has been determined by using immunoprecipitation with spore protein antibody. SP170, SP103, 'SP94', SP82, SP76 and SP55 are all first synthesized just prior to the 'Mexican hat' stage of development (16-18h), but the synthesis of SP72 is delayed. This protein is apparently synthesized as a precursor, P66, which is modified during spore maturation to yield SP72. The nature of the modification is unknown. At their peak period of synthesis during early culmination (18-20h), the spore coat proteins account for 5-9% of total protein synthesis. Shortly after synthesis, these proteins are inserted into the spore coat, where all except SP103 become disulphide-cross-linked during the period 24-30h. SP3 does not accumulate until disulphide-cross-linking of the major spore coat proteins occurs and is itself disulphide-cross-linked into the spore coat. Several additional proteins that are accumulated during development have also been identified, namely P31, P25, P21 and P18. P25 first appears at 18-20h and then continues to be made throughout development. P31 synthesis begins at 12-14h and then largely ceases after approx. 20 h of development. The genes for both P21 and P18 are first expressed early in development, starting at 9-12h. P21 synthesis ceases at approx. 14h, but P18 continues to be synthesized throughout the rest of development. The marked differences in the time period of accumulation of these proteins compared with the co-ordinated syntheses of SP170, SP103, 'SP94', SP82, SP76 and SP55 provide a useful system for analysis of the mechanism of temporal gene expression during development.

Cell Membrane↗