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J Revill

Publications and source records attributed to J Revill.

11 recordsLinked to original sources
PubMed1997

Capital punishment.

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Health Care Reform↗
PubMed1991

Genetic evidence that the putative receptor binding domain of apolipoprotein B (residues 3130 to 3630) is not the only region of the protein involved in interaction with the low density lipoprotein receptor.

We have searched for sequence differences in the region of the apolipoprotein B (apo B) gene encoding amino acids 3130-3630 in eight individuals with reduced affinity of low density lipoprotein (LDL) for the normal LDL-receptor. All individuals were hypercholesterolaemic and were selected either on the basis of reduced fractional catabolic rate (FCR) of autologous LDL or substantially reduced binding of their LDL to normal LDL-receptors determined by an in vitro cell growth assay using the U937 macrophage-like cell line. Segments of the apo B gene were amplified by the polymerase chain reaction. Using a combination of cloning and sequencing the amplified fragment, together with chemical cleavage mismatch analysis, no sequence differences were identified in this region of the gene. We therefore conclude that variation outside the region of the apo B gene that codes for amino acids 3130-3630 must be responsible for the reduced LDL clearance in these patients.

Apolipoproteins B↗
PubMed1990

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives.

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

Administration, Oral↗
PubMed1988

The fractional catabolic rate of low density lipoprotein in normal individuals is influenced by variation in the apolipoprotein B gene: a preliminary study.

In a random sample of 22 normolipidaemic male Caucasian individuals, 35-49 years old, homozygosity for the X2 allele (cutting site) of the XbaI RFLP of the apo B gene was associated with higher mean total cholesterol and LDL-cholesterol concentration. These individuals also had significantly lower LDL fractional catabolic rate (P less than 0.03) and a lower degradation of LDL by mononuclear cells in vitro. We propose that the XbaI polymorphism is associated with amino acid changes in the apo B protein which influences LDL binding to the LDL-receptor. This modulates catabolism of this lipoprotein and so contributes to variability of plasma cholesterol levels.

Adult↗
PubMed1984

Metabolic study of variation in plasma cholesterol level in normal men.

Variation in plasma cholesterol in normal populations underlies a 2-5 fold range of risk of coronary heart disease. The metabolic basis of this variation was studied in a healthy population recruited from a general-practice list. Compared with men in the modal decile of plasma cholesterol, those in the top decile maintained their high levels by overproduction of low-density lipoprotein (LDL). Men in the bottom decile of plasma cholesterol had low levels of LDL, resulting chiefly from a greater rate of fractional catabolism of this lipoprotein; and blood mononuclear cells from men in the bottom decile catabolised LDL more rapidly in vitro than did cells from other men. Intake of dietary lipids by men in the top, modal, and bottom deciles did not differ significantly. Different mechanisms appear to underlie high and low levels of plasma cholesterol in a normal population.

Adult↗