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Biomedical subjects

J Lloyd

Publications and source records attributed to J Lloyd.

At least 145 records · Page 8Linked to original sources
PubMed1988

Phosphorylation of the GABAa/benzodiazepine receptor alpha subunit by a receptor-associated protein kinase.

Partially purified preparations of GABAa/benzodiazepine receptor from rat brain were found to contain high levels of a protein kinase activity that phosphorylated a small number of proteins in the receptor preparations, including a 50-kilodalton (kD) phosphoprotein that comigrated on two-dimensional electrophoresis with purified, immunolabeled, and photolabeled receptor alpha subunit. Further evidence that the comigrating 50-kD phosphoprotein was, in fact, the receptor alpha subunit was obtained by peptide mapping analysis: the 50-kD phosphoprotein yielded one-dimensional peptide maps identical to those obtained from iodinated, purified alpha subunit. Phosphoamino acid analysis revealed that the receptor alpha subunit is phosphorylated on serine residues by the protein kinase activity present in receptor preparations. Preliminary characterization of the receptor-associated protein kinase activity suggested that it may be a second messenger-independent protein kinase. Protein kinase activity was unaltered by cyclic AMP, cyclic GMP, calcium plus calmodulin, calcium plus phosphatidylserine, and various inhibitors of these protein kinases. Examination of the substrate specificity of the receptor-associated protein kinase indicated that the enzyme preferred basic proteins as substrates. Endogenous phosphorylation experiments indicated that the receptor alpha subunit may also be phosphorylated in crude membranes by a protein kinase activity present in those membranes. As with phosphorylation of the receptor in purified preparations, its phosphorylation in crude membranes also appeared to be unaffected by activators and inhibitors of second messenger-dependent protein kinases. These findings raise the possibility that the phosphorylation of the alpha subunit of the GABAa/benzodiazepine receptor by a receptor-associated protein kinase plays a role in modulating the physiological activity of the receptor in vivo.

Animals↗
PubMed1987

Human muscle carbonic anhydrase: gene structure and DNA methylation patterns in fetal and adult tissues.

We report the isolation and analysis of genomic clones comprising the entire gene coding for the human muscle carbonic anhydrase, CAIII. The gene spans 10.3 kb and has a seven-exon/six-intron structure. A noncanonical TATA box, a CCAAT motif, and two CCGCCC elements are present in the sequences upstream of exon 1. Although the expression of CAIII shows strict tissue specificity, the gene exhibits a number of features normally associated with housekeeping enzymes. For example, there is 48% homology with a 25-bp consensus sequence between the TATA box and the cap site and there is a CpG-rich island spanning a 469-bp sequence near to the origin of transcription. Methylation studies suggest that some CCGG sites clustered in the CpG-rich island are undermethylated in DNA from fetal and adult muscle and in other tissues irrespective of CAIII expression. In contrast, several nonclustered CCGG sites show a methylation pattern that correlates with gene expression. However DNA from differentiated type II adult muscle fibers is undermethylated at these sites even though CAIII is not expressed.

Adult↗
PubMed1987

Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1-2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/- 1.9 h (mean +/- s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Adolescent↗
PubMed1986

Nucleotide sequence and derived amino acid sequence of a cDNA encoding human muscle carbonic anhydrase.

We report the nucleotide (nt) sequence of a full length cDNA clone, pCA15, which encodes the human muscle-specific carbonic anhydrase, CAIII. pCA15 identifies a 1.7-kb mRNA, which is present at high levels in skeletal muscle, at much lower levels in cardiac and smooth muscle and which appears to be developmentally regulated. The CAIII mRNA is distinguished by a 887-nt long 3'-untranslated region, containing two AAUAAA signal sequences and is longer than either of the mRNAs encoding the erythrocyte CAs, CAI and CAII, which each have relatively shorter 3'-untranslated regions, 360 and 670 nt long, respectively. The derived amino acid (aa) sequence for human CAIII shows 85% homology with ox CAIII, 62% homology with human CAII and 54% with human CAI when simple pairwise aa comparisons are made. We describe an allelic variation at a TaqI restriction site for CAIII which occurs at high frequency in the European population.

Amino Acid Sequence↗
PubMed1986

The gene for human muscle specific carbonic anhydrase (CAIII) is assigned to chromosome 8.

A cDNA clone complementary to the mRNA encoding the human muscle specific carbonic anhydrase CAIII has been used as probe in the analysis of DNA from panels of rodent/human somatic cell hybrids. The presence of the CA III gene in all hybrids correlates with the presence of chromosome 8. This is the first assignment of the CAIII gene in any species and, together with published mapping data, indicates that all of the human CA loci are situated on chromosome 8.

Animals↗
PubMed1986

Visualization of binding sites for bovine parathyroid hormone (PTH 1-84) on cultured kidney cells with a biotinyl-b-PTH (1-84) antagonist.

Parathyroid hormone (PTH) receptors have been found in a subpopulation of kidney cells. In this report, we investigated the feasibility of techniques that apply a partial antagonist of PTH conjugated to biotin to localize receptors cytochemically on bovine kidney cortical cells in monolayer culture at the light microscopic level. Biotinylated bovine PTH (1-84) (biotinyl-PTH) was bound to the cultured cells for 1-30 min at 37 degrees C in the amounts of 10(-5) -10(-10) M. In a different set of experiments, the cells were also exposed to a solution containing 10(-6) M biotinylated PTH and an excess of unlabeled PTH, insulin, adrenocorticotropin, or calcitonin for 10 and 30 min at 37 degrees C to test the specificity of the binding. The cells were then fixed in 2.5% glutaraldehyde and stained with the avidin-biotin peroxidase complex (ABC) technique. Diffuse labeling was evident on 30% of the cells in 10 min with concentrations of biotinyl-PTH as low as 10(-8) M. The stain was diffuse, but more intense after 1-10 min in higher concentrations (10(-6) M). If a 15-1500-fold excess of unlabeled PTH was added to the biotinyl-PTH, no staining was observed. The other peptides (insulin, ACTH or calcitonin) had no effect on binding. Longer times in biotinyl-PTH (10(-6) M for 10-30 min) resulted in intense patches of label on the cells resembling caps (in addition to the pale diffuse label). The percentage of labeled cells in the monolayer (30%) did not change with time. These studies show that a partial antagonist of PTH can be used as a cytochemical probe for specific PTH receptors in a subpopulation of cultured cortical kidney cells.

Animals↗
PubMed1986

The place of sodium hyaluronate in glaucoma surgery.

The advantages of sodium hyaluronate (Healon) in filtering surgery have been mostly theoretical, with no study of sufficient numbers to justify its use. The authors used sodium hyaluronate in 119 consecutive trabeculectomies. These were compared to a control group of 122 cases. The long-term intraocular pressure and visual acuity results between the two groups were indistinguishable. The only definite benefit noted with the use of sodium hyaluronate was the lower incidence of hyphemas. No side-effects were seen. Its ability to maintain a deep anterior chamber and encourage hemostasis makes sodium hyaluronate useful in teaching goniotomies as well as performing trabeculectomies in congenital glaucoma. Sodium hyaluronate can also be used to evacuate hyphemas and dissect adhesions with minimal trauma, and may be healthier for the corneal endothelium than air in anterior chamber reformations.

Aged↗
PubMed1985

Treatment of homozygous familial hypercholesterolaemia: an informative sibship.

In a family in which both parents had the heterozygous form of familial hypercholesterolaemia four of the children had the homozygous form. The three oldest homozygous children, two of whom did not receive any treatment and in one of whom treatment did not lower the plasma cholesterol concentration, developed xanthomas in early childhood and died aged 3, 9, and 10 years. The fourth homozygous child was treated with diet and drugs from the age of 1 and at the age of 15 had no xanthomas, no clinical evidence of heart disease, and a virtually normal coronary angiogram. His plasma cholesterol concentration was reduced by about 30% but remained considerably raised. It is concluded that treatment, if started before atherosclerosis develops, can delay the onset of atheroma and coronary heart disease even though normal plasma cholesterol concentrations are not achieved.

Adolescent↗
PubMed1985

Sequelae and support after termination of pregnancy for fetal malformation.

A retrospective study examined the reactions to the termination of pregnancy for fetal malformation and the follow up services that were available. Women resident in Mid Glamorgan who had had a termination between 1977 and 1981 because of positive findings after midtrimester prenatal diagnostic tests for neural tube defect or chromosome abnormalities were interviewed at home using a semistructured interview schedule. Three retrospective internal comparison groups were formed from those women who had also had a spontaneous abortion, previous stillbirth, or neonatal death or previous termination for medicosocial reasons early in pregnancy. Of the 48 women interviewed, 37 (77%) experienced an acute grief reaction after the index pregnancy was ended. This reaction was akin to that documented after stillbirth or neonatal death. Twenty two women (46%) remained symptomatic six months after the pregnancy had been ended, some requiring psychiatric support, compared with no such reaction after spontaneous abortion or termination for medicosocial reasons. All the women who had previously had a stillbirth or neonatal death were visited at home either by the general practitioner or by the midwife after that event but such follow up was limited to only eight of the study group after termination for fetal malformation. The findings suggest that support is inadequate for these patients and that improved follow up and counselling services may lessen the adverse sequelae of termination for fetal malformation.

Abortion, Induced↗
PubMed1984

The 3'-untranslated sequence of human skeletal muscle alpha-actin mRNA.

A human actin cDNA clone pGF3 isolated from a fetal skeletal muscle cDNA library is described. The insert cDNA is homologous to skeletal muscle alpha-actin as judged by restriction mapping and nucleotide sequencing. The recombinant contains a substantial portion of the coding and the complete 3'-untranslated region. Comparison of the 3' ends of human and rat skeletal muscle and human cardiac alpha-actins reveals little homology between different types of actin genes in man but marked conservation of this region in the skeletal muscle actins of man and rat.

Actins↗
PubMed1984

Pulmonary hypersensitivity in the alginate industry.

Salts of alginic acid are complex polymerised polysaccharides which are chemically extracted from seaweed. Workers in the alginate industry are exposed to dust from dried milled seaweed and pure alginate compounds. In this survey of one of the two factories in Britain producing alginates, we found evidence of pulmonary hypersensitivity to seaweed dust in seven per cent of the total work force, and evidence of precipitating antibody to sodium alginate and seaweed extracts in the serum of 4.5 per cent of the work force. Challenge testing of a number of employees with symptoms showed a dual response with immediate airways obstruction, and a later loss of lung volume, with associated impairment of transfer factor.

Alginates↗