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Biomedical subjects

P Sweetnam

Publications and source records attributed to P Sweetnam.

7 recordsLinked to original sources
PubMed1991

Sequence and expression of a neuropeptide Y receptor cDNA.

The polymerase chain reaction was used to isolate novel GTP-binding protein (G protein)-coupled receptors from bovine locus coeruleus (LC), a brain region enriched in the neuropeptide Y (NPY) system, using degenerate primers derived from the third and sixth transmembrane domains of known G protein-coupled receptors. Partial sequence analysis revealed that the polymerase chain reaction cDNA fragments were homologous to other G protein-coupled receptors. One of these cDNA fragments was used to isolate a full length cDNA clone, referred to as LCR1, from an LC cDNA library. LCR1 is 1.7 kilobases in length and encodes a predicted protein of 353 amino acids, with a membrane topology similar to that of other G protein-coupled receptors. Expression of LCR1 in mammalian cells revealed saturable and specific high affinity binding for 125I-NPY but not for any of the other ligands tested. Northern blot analysis revealed that labeled LCR1 DNA hybridized with a predominate mRNA transcript of approximately 1.7 kilobases, which was found to be most abundant in LC, cerebellum, and pons, intermediate in dorsal raphe, substantia nigra, and thalamus, and lowest in cerebral cortex and neostriatum. Significant levels of LCR1 mRNA were also present in heart, kidney, lung, and liver. This cDNA clone will be useful for studies of the regulation and function of NPY receptors, as well as for the isolation of related NPY receptor subtypes.

Amino Acid Sequence↗
PubMed1987

Comparison of the molecular structure of GABA/benzodiazepine receptors purified from rat and human cerebellum.

The use of improved affinity chromatographic techniques has allowed for the substantial copurification of both the benzodiazepine and the GABA receptor from brain. These preparations have been used to begin characterization of the benzodiazepine receptor at a molecular level. We have recently purified benzodiazepine receptor from human and rat cerebellum, and SDS-PAGE has revealed that both preparations consist of a major protein of 50 kDa and a minor protein of 55 kDa. These proteins are recognized by a series of monoclonal antibodies prepared against the rat benzodiazepine receptor suggesting the rat and human receptors share several common antigenic domains. Several other approaches have been employed to further investigate possible homology between the rat and human receptors. Proteolytic degradation studies have shown that the major limiting photolabeled peptide fragment generated in rat and human is similar as determined by HPLC analysis. Isoelectric focusing and SDS (two-dimensional) electrophoresis have revealed that the immunoreactive, photolabeled 50 kDa protein, and the purified receptor have identical PI values. The receptor from both human and rat are glycoproteins as determined by lectin binding studies. However, exposure of these proteins to neuraminidase fails to alter the pharmacology of the receptors indicating possible similarities in their posttranslational glycosylation. Thus, it appears that some degree of structural homology exists between the rat and human benzodiazepine receptors.

Animals↗
PubMed1979

The outcome of pregnancy after cone biopsy of the cervix: a case-control study.

We investigated the outcome of pregnancy after cone biopsy of the cervix. We found that preterm delivery and low birth weight were commoner and the mean duration of labour longer in women who had a cone biopsy than amongst matched controls. Rapid labour (under two hours) was not significantly more common after cone biopsy.

Abortion, Spontaneous↗
PubMed1977

Temperature and deaths from ischaemic heart disease.

Certain features of the relationship between 11 measurements of weekly temperature and the number of deaths from ischaemic heart disease (IHD) within age groups in Greater London between 1970 and 1974 are described. Firstly, the correlation coefficients between age-specific deaths from IHD and each of the temperature variables are of a similar order. Secondly, in contrast, the linear regression coefficients between deaths and temperature are more variable and depend upon the particular measurement of temperature chosen. Thirdly, the proportional changes in the number of deaths with the temperature variables are similar within specific age groups; consequently it is suggested that deaths from IHD and temperature may be directly related.

Adult↗
PubMedDate not supplied

Variation of apolipoprotein-B gene is associated with obesity, high blood cholesterol levels, and increased risk of coronary heart disease.

A random sample of 290 white men was examined for association between restriction fragment length polymorphism (RFLP) haplotypes (closely linked RFLPs on a single chromosome) of the apolipoprotein-B gene and serum levels of cholesterol, triglyceride, and high-density lipoprotein, obesity, smoking, alcohol consumption, and coronary heart disease. Haplotype or single RFLP frequencies differed significantly for obesity (p less than 0.005), serum cholesterol (p less than 0.005), and coronary heart disease (p less than 0.05), but for no other variable. Obesity was associated with haplotypes involving minimum PvuII and XbaI RFLPs are likely to be in linkage disequilibrium with nearby functional variation predisposing to obesity. Significant variation in serum cholesterol levels was associated with three functional alleles defined by MspI and EcoRI RFLP pairs (p less than 0.03). These RFLPs correspond to charged aminoacid variants at positions 3611 (arginine to glutamine) and 4154 (glutamic acid to lysine), which lie near the low-density-lipoprotein (LDL) receptor binding region of apolipoprotein-B. The three alleles showed stratification of serum cholesterol between low, normal, and high levels. Coronary heart disease was associated with minimum haplotypes involving XbaI and MspI RFLPs. Together these results suggest that inherited variations of the apolipoprotein-B gene, probably in the form of charged aminoacid substitutions, influence circulating cholesterol concentration, and that these and other functional variants of the apolipoprotein-B gene affect susceptibility to coronary heart disease and obesity.

Aged↗