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Biomedical subjects

R J Beynon

Publications and source records attributed to R J Beynon.

At least 91 records · Page 5Linked to original sources
PubMed1985

Proximity of the Mep-1 gene to H-2D on chromosome 17 in mice.

The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1b allele. Mouse strains in which meprin activity levels are normal are designated Mep-1a. Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1a F1 hybrids [C3H.A (KkDd) X C3H.OH (KdDk)] were backcrossed with Mep-1b C3H.OH (KdDk) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.

Amino Acids, Sulfur↗
PubMed1985

Accelerated degradation of glycogen phosphorylase in denervated and dystrophic mouse skeletal muscle.

Pyridoxal phosphate, the cofactor of glycogen phosphorylase, fulfils the criteria needed of a turnover label for this enzyme. The decay of protein-bound label following administration of [3H]pyridoxine is a good index of the rate of degradation of the enzyme in vivo. This method has been applied to the study of catabolism of the enzyme in normal, denervated and dystrophic mouse skeletal muscle. In both of the pathological conditions the enzyme is degraded more rapidly than normal.

Animals↗
PubMed1985

A general purpose non-linear curve fitting program for the British Broadcasting Corporation Microcomputer.

Software for non-linear curve fitting has been written in BASIC to execute on the British Broadcasting Corporation Microcomputer. The program uses the direct search algorithm Pattern-search, a robust algorithm that has the additional advantage of needing specification of the function without inclusion of the partial derivatives. Although less efficient than gradient methods, the program can be readily configured to solve low-dimensional optimization problems that are normally encountered in life sciences. In writing the software, emphasis has been placed upon the 'user interface' and making the most efficient use of the facilities provided by the minimal configuration of this system.

Algorithms↗
PubMed1985

Computers.

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Biology↗
PubMed1985

Software.

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Software↗
PubMed1984

Purification of glycogen phosphorylase from small quantities of mouse skeletal muscle.

A new approach to the purification of skeletal muscle glycogen phosphorylase is described. The purification scheme is particularly suited to preparation of the enzyme from small amounts of tissue. A combination of dye-ligand chromatography and hydrophobic chromatography yields homogenous enzyme with good recoveries. The purification is rapid and may be completed in a working day.

Acrylic Resins↗
PubMed1984

Mep-1 gene controlling a kidney metalloendopeptidase is linked to the major histocompatibility complex in mice.

Meprin, a glycoprotein with potent metalloendopeptidase activity, is an integral component of the brush border membrane of mouse kidney. Previously we reported that genealogically related inbred mouse strains (C3H and CBA) are markedly deficient in the activity of this enzyme. We report here that meprin deficiency is inherited as an autosomal recessive trait and that several other inbred strains also express low levels of meprin activity. All of the inbred strains deficient in meprin activity are of the H-2k haplotype; however, two strains of this haplotype (C58 and C57BR/cd) expressed normal levels of the proteinase. Congeneic and recombinant mouse strains were examined to determine whether the deficiency was linked to the H-2 complex. The gene controlling the activity of meprin (Mep-1) maps on chromosome 17 to the right of the D end of the major histocompatibility complex. The Mep-1 gene is closely linked to a gene that controls isoenzyme patterns of phosphoglycerate kinase (Pgk-2). This work represents the localization of a gene that determines the activity of an integral cellular endopeptidase in mammalian tissues. In addition, the Mep-1 gene is the only identified gene linked to the major histocompatibility complex that regulates a proteinase activity.

Alleles↗
PubMed1984

Synthetic analogues of the proteinase inhibitor: chymostatin.

Putative proteinase inhibitors with the general structure Z. Arg. X.Phe.H (where X = Leu, Ile or Val) were prepared by solution synthesis using semicarbazone protection for the aldehyde function. These inhibitors showed strong activity towards chymotrypsin whereas the semicarbazones and dipeptides aldehydes showed considerably reduced activity. The structural requirements for inhibition would seem to mimic those of the natural chymotrypsin inhibitor chymostatin.

Chymotrypsin↗
PubMed1983

Inhibition of hepatic protein degradation by synthetic analogues of chymostatin.

Analogues of the microbial proteinase inhibitor chymostatin have been synthesized. The two most promising analogues were tested on protein turnover in isolated rat hepatocytes. Their effect is much similar to the effect of chymostatin, but the analogues are even more powerful inhibitors, probably due to an increased effect on lysosomal thiol proteinases. The analogues blocked most of the lysosomal (i.e. methylamine-sensitive) degradation of endogenous protein and caused a 50% inhibition of the non-lysosomal degradation; the effect occurred rapidly and was reversed upon washing the cells. One of the analogues, Z-Arg-Leu-Phe(H), is the most potent inhibitor of hepatic protein degradation so far found.

Animals↗
PubMed1983

Chymotryptic activation of glutamate dehydrogenase.

Treatment of bovine liver glutamate dehydrogenase (L-glutamate:NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) with chymotrypsin generates a proteolytic derivative that is activated 3-4-fold over the native enzyme. Stable preparations of activated enzyme show altered kinetic parameters (5-fold increase in Km for glutamate, 3-fold increase in Vmax) and altered response to allosteric modulation by GTP and ADP. The proteolysed enzyme was less responsive to GTP and was no longer activated by ADP, although ADP binding sites remained intact on the enzyme. The effect of ADP upon substrate inhibition was altered and negative homotropic interactions in coenzyme binding were abolished.

Adenosine Diphosphate↗
PubMed1983

Deficiency of a kidney metalloproteinase activity in inbred mouse strains.

Kidneys from BALB/c mice contain a potent metalloendoproteinase, termed meprin, that is active against large proteins as well as small peptides. The enzyme is present in mouse strains C57BR/cdJ, C57BL/6J, BALB/cJ, A/J, DBA/IJ, CD/l, Swiss, and ICR. Three related inbred strains, CBA/J, CBA/CaJ, and C3H/He, are markedly deficient in this enzymatic activity. This is the first report of a heritable deficiency of an intracellular proteinase in mammalian tissues. Meprin deficiency appears to have arisen as an early event in the development of the C stock. Furthermore, meprin is present in the progeny of a cross between a meprin-sufficient female (C57BL/6) and a meprin-deficient male (C3H/HeN), an indication that the trait for the deficiency is recessive.

Amino Acids, Sulfur↗