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Biomedical subjects

L Morgan

Publications and source records attributed to L Morgan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion.

Alleles↗
PubMed1998

Urinary neopterin as a prognostic index of survival time in HIV-1 infection.

A prospective semi-longitudinal study was undertaken to determine if urinary neopterin was a predictor for survival in HIV-positive patients. One hundred and one HIV-positive subjects attending a department of genitourinary medicine over a 41-month period were included. Survival data were analysed 6 months after the end of recruitment. Ninety-two subjects were followed up for a minimum of 6 months. Survival figures at 1 and 2 years were 93% (SE 3%) and 79% (SE 5%). There was an inverse relationship between urinary neopterin excretion and 1 and 2-year survival. Two-year survival fell from 70% (SE 6%) for neopterin levels > or = 300 mmol/mol creatinine to 25% (SE 9%) for levels > or = 700 mmol/mol creatinine (P < 0.001). Urinary neopterin may be a useful non-invasive technique in predicting survival in HIV-positive patients.

CD4 Lymphocyte Count↗
PubMed1998

Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism.

This study was undertaken to determine whether the internal clock contributes to the hormone and metabolic responses following food, in an experiment designed to dissociate internal clock effects from other factors. Nine female subjects participated. They lived indoors for 31 days with normal time cues, including the natural light: darkness cycle. For 7 days they retired to bed from 0000 h to 0800 h. They then underwent a 26-h 'constant routine' (CR) starting at 0800 h, being seated awake in dim light with hourly 88 Kcal drinks. They then lived on an imposed 27-h day (18 h of wakefulness, 9 h allowed for sleep), for a total of 27 days. A second 26-h CR, starting at 2200 h, was completed. During each CR salivary melatonin and plasma glucose, triacylglycerol (TAG), non-essential fatty acids (NEFA), insulin, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured hourly. Melatonin and body temperature data indicated no shift in the endogenous clock during the 27-h imposed schedule. Postprandial NEFA, GIP and GLP-1 showed no consistent effects. Glucose, TAG and insulin increased during the night in the first CR. There was a significant effect of both the endogenous clock and sleep for glucose and TAG, but not for insulin. These findings may be relevant to the known increased risk of cardiovascular disease amongst shift workers.

Adult↗
PubMed1998

Altered postprandial hormone and metabolic responses in a simulated shift work environment.

The circadian rhythms of most night shift workers do not adapt fully to the imposed behavioural schedule, and this factor is considered to be responsible for many of the reported health problems. One way in which such disturbances might be mediated is through inappropriate hormonal and metabolic responses to meals, on the night shift. Twelve healthy subjects (four males and eight females) were studied on three occasions at the same clock time (1330 h), but at different body clock times, after consuming test meals, first in their normal environment, secondly after a forced 9 h phase advance (body clock time approximately 2230 h) and then again 2 days later in the normal environment. They were given a low-fat pre-meal at 0800 h, then a test meal at 1330 h with blood sampling for the following 9 h. Parameters measured included plasma glucose, non-esterified fatty acids (NEFAs), triacylglycerol (TAG), insulin, C-peptide, proinsulin and glucose-dependent insulinotropic polypeptide, and urinary 6-sulphatoxymelatonin. In contrast with a previous study with a high-fat pre-meal, postprandial glucose and insulin responses were not affected by the phase shift. However, basal plasma NEFAs were lower immediately after the phase shift (P < 0.05). Incremental (difference from basal) TAG responses were significantly higher (P < 0.05) immediately after the phase shift compared with before. Two-day post-phase shift responses showed partial reversion to baseline values. This study suggests that it takes at least 2 days to adapt to eating meals on a simulated night shift, and that the nutritional content of the pre-meals consumed can have a marked effect on postprandial responses during a simulated phase shift. Such findings may provide a partial explanation for the increased occurrence of cardiovascular disease reported in shift workers.

Adult↗
PubMed1998

Hematology and chemistry reference values for free-ranging harbor seals (Phoca vitulina) and the effects of hemolysis on chemistry values of captive harbor seals.

Most reported laboratory reference values for harbor seals (Phoca vitulina) are derived from captive seals, or stranded seals that have recovered from disease in marine mammal centers. This study established hematology and serum chemistry reference values for free-ranging harbor seals, using methods and that are current and readily available, and determined the effects of hemolysis on serum chemistry values of captive harbor seals. Blood samples were collected for hematologic and serum chemistry measurements from 14 clinically normal, adult male and female harbor seals and two juvenile harbor seals (approximate age 6 mo) captured in saltwater sloughs and estuaries near Moss Landing, California, USA. Values for amylase, globulin, and differential leukocyte count, not previously reported, were determined. In general, hematology and chemistry values in adults were similar to those reported for free-ranging and captive harbor seals, except for glucose, urea nitrogen, and lactate dehydrogenase (LDH) values, which were higher than those reported previously. Red blood cell counts in the two juveniles were higher than in adults and in young harbor seals studied previously. To determine the effects of hemolysis on serum chemistry values, two intensities of hemolysis were generated experimentally in blood collected from 11 harbor seals recovering from injuries or stranding at the Marine Mammal Center (Sausalito, California 94965, USA). Moderate hemolysis (++, 1 g/L hemoglobin, red-tinged) significantly increased LDH activity, whereas severe hemolysis ( , 2 g/L hemoglobin, cherry red) significantly increased total protein, albumin, calculated globulin, LDH, and total bilirubin and significantly decreased creatinine. The effects of hemolysis must be considered when chemistry results of harbor seals are interpreted.

Animals↗
PubMed1997

Microsatellite polymorphism of the alpha 1-antichymotrypsin gene locus associated with sporadic Alzheimer's disease.

A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer's disease (AD) and a subset of familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and alpha 1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated with AD. We now show that a dinucleotide microsatellite allele in the 5'-flanking sequence of the ACT gene, designated A10, in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of AD cases.

Aged↗
PubMed1997

Elevated post-prandial gastric inhibitory polypeptide concentrations in hypertriglyceridaemic subjects.

1. We investigated whether abnormalities of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1) contribute to the hypertriglyceridaemia and hyperinsulinaemia in hypertriglyceridaemic subjects. Serum triglycerides and plasma glucose GIP, GLP-1 and immunoreactive insulin (IRI) concentrations were measured before and after a mixed meal in 15 hypertriglyceridaemic patients and in eight healthy normotriglyceridaemic control subjects. 2. Integrated post-prandial GIP concentrations were greater than in controls (P < 0.05) and correlated positively with both fasting and integrated post-prandial triglyceride concentrations (P < 0.05 for both). Fasting and integrated post-prandial IRI levels were higher in hypertriglyceridaemic subjects than in controls (P < 0.02 and P < 0.05 respectively) and correlated positively with fasting triglycerides (P < 0.02 and P < 0.001 respectively) and integrated post-prandial triglycerides (P < 0.005 and P < 0.05 respectively). There was no correlation between GIP concentrations and either fasting or post-prandial IRI levels. Fasting and post-prandial concentrations of GLP-1 were similar in patients and controls. 3. Hypertriglyceridaemic subjects have post-prandial hyperGIPaemia in addition to the well-documented hyperinsulinaemia. We found no association between GIP and insulin. There is, however, clear evidence for an association between post-prandial GIP concentrations and triglyceride levels. We suggest that this association may depend on changes in lipoprotein lipase activity and that there may be a feedback loop between GIP and triglyceride lipolysis.

Adult↗
PubMed1997

The effects of vitamin A derivatives on in vitro antibody production by peripheral blood mononuclear cells (PBMC) from normal blood donors and patients with common variable immunodeficiency (CVID).

The underlying nature of the defect of CVID is not understood, and the treatment at present is life-long infusion of replacement immunoglobulin. Attempts have been made to use other therapeutic agents, such as IL-2 and retinoic acid (RA), with mixed results. RA is a morphogenetic signalling molecule related to vitamin A and involved in vertebrate development. We report here our in vitro evaluation of the effects of three vitamin A analogues, 9-cis retinal, 13-cis RA and all-trans RA, on antibody production of PBMC from normal donors and patients with CVID. At 10(-5) M, 9-cis retinal strongly augmented IgM production of lymphocytes from normal individuals and to a much lesser extent, mild, non-granulomatous (group C) CVID patients, but IgG production was not affected. In the presence of anti-human IgM and IL-2, 9-cis retinal at 10(-5) M elevated IgM and IgG production by normal PBMC, but the effect on PBMC of mild CVID was minimal. The effect of 9-cis retinal was significantly reduced at 10(-7) and 10(-9) M. Only minimal effects were found using 13-cis RA and all-trans RA under these conditions. No detectable antibody production was found in severe, granulomatous (group A) CVID patients under any conditions tested. Taking all data into account, 9-cis retinal is the most potent stimulator for antibody production compared with 13-cis RA and all-trans RA as tested in this in vitro study.

Blood Donors↗
PubMed1997

Functional and genetic studies of the angiotensin II type 1 receptor in pre-eclamptic and normotensive pregnant women.

OBJECTIVE: To examine and compare angiotensin II type 1 receptor genotype and its relationship to platelet angiotensin II binding for pre-eclamptic and normotensive pregnant women. DESIGN: In a case-control study, 43 pre-eclamptic women and 83 normotensive women were genotyped at the angiotensin II type 1 receptor gene locus. Platelet angiotensin II binding was measured for a subset of 11 pre-eclamptic and 57 normotensive pregnant women. We genotyped 162 healthy blood donors also, to examine the allelic background and patterns of linkage disequilibrium in the Nottingham population. METHODS: Patients were recruited during pregnancy using a rigorous definition of pre-eclampsia. DNA was extracted from peripheral venous blood and genotyped at six previously described diallelic polymorphisms in the angiotensin II type 1 receptor gene, using competitive allele-specific oligonucleotide hybridization, and at a dinucleotide repeat polymorphism in the 3' flanking region of the gene. Platelet angiotensin II binding and plasma angiotensin II concentrations were determined for peripheral venous blood. RESULTS: Normotensive pregnant women homozygous for cytosine at nucleotide 573 had significantly higher levels of platelet angiotensin II binding than did heterozygous women and women homozygous for thymidine at this site. Pre-eclamptic women had significantly higher levels of platelet angiotensin II binding than did normotensive pregnant women. The frequencies of allelic variants did not differ significantly between normotensive and pre-eclamptic women. CONCLUSION: The physiological regulation of platelet angiotensin II type 1 receptor expression in normal pregnancy is determined in part by angiotensin II type 1 receptor genotype. There was no evidence that the polymorphisms in the angiotensin II type 1 receptor gene were associated with pre-eclampsia.

Adult↗
PubMed1997

Soluble IL-6R in plasma cell dyscrasias.

The understanding of the biology of multiple myeloma has advanced significantly in the past few years. The identification of the pivotal role of Interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), and how the ligand receptor complex interacts with the signal transducer gp130 has provided new biological insights into plasma cell disorders. Some studies have suggested that sIL-6R levels may have prognostic significance in MM, however this is not a consistent finding. Here the biology and function of IL-6 and sIL-6R are reviewed and the clinical significance of sIL-6R discussed.

Humans↗
PubMed1997

Protein phosphorylation and the regulation of cell-cell junctions in brain endothelial cells.

Endothelial cells lining the capillaries of the brain have two properties that distinguish them from their peripheral counterparts: (1) tight junctions of extremely low permeability; and (2) low rates of fluid-phase endocytosis. In combination, these features limit the nonspecific flux of ions, proteins, and other substances into the central nervous system environment, creating the blood-brain barrier. This barrier is not immutable. Tight junction permeability can be rapidly increased, which may play a role in the development of a variety of brain pathologies. We have therefore been interested in mechanisms regulating junctional permeability and strategies for interfering with this regulation. What is becoming increasingly apparent is that junctions are not passive mechanical entities; rather, they are targets for a variety of signaling pathways.

Animals↗
PubMed1996

Catalytic and EPR studies of the beta E204Q mutant of the chloroplast F1-ATPase from Chlamydomonas reinhardtii.

The mutation E204Q in the beta subunit of the chloroplast F1-ATPase was made by biolistic transformation of Chlamydomonas reinhardtii. The yield of chloroplast F1-ATPase (CF1) purified from thylakoids was unaltered, suggesting that the mutation did not affect protein assembly. However, photoautotrophic growth of Chlamydomonas strains containing beta E204Q was virtually abolished, and the effect of the mutation on the light-driven ATPsynthase activity catalyzed by purified thylakoids was comparable to the change in the photoautotrophic growth rate. The loss of ATPsynthase activity in the mutant was not the result of uncoupling. Addition of wild-type CF1 to mutant thylakoids depleted of CF1 reconstituted ATPsynthase activity indicating that the mutation did not affect assembly of F0. Furthermore, the mutant CF1F0 was capable of catalyzing ATPase-dependent proton pumping as measured by fluorescence quenching of 9-amino acridine. Although the mutation significantly affected the apparent kcat/K(m) of the Mg(2+)-ATPase activity of the purified CF1-ATPase, no significant effect on the apparent kcat was observed with the mutant compared to wild-type. No significant changes in the ability of Mg2+ or Mn2+ to serve either as a cofactor or as an inhibitor of ATPase activity were observed in the mutants relative to the wild-type CF1-ATPase. EPR spectra were also taken of VO2+ bound at catalytic site 3 in its latent form. In a large fraction of the latent enzyme, a carboxyl group has displaced the nucleotide-phosphate coordination to the metal which results in the free-metal inhibited form (M3). No significant effects on the gII and AII 51V hyperfine parameters were observed between wild-type and mutant. However, the mutation increased the abundance of the M3 form relative to the M3-N3 form (metal-nucleotide-coordinated form). On the basis of these results, beta E204 is not the carboxyl group that displaces the nucleotide phosphate as a ligand to form the free-metal inhibited enzyme form which predominates in site 3 in the latent state. Instead, the data are consistent with a role in which beta E204 is essential to protonate an inorganic phosphate-oxygen to make that oxygen a good leaving group to facilitate ATP synthesis and, via this role in H-bonding, increases the abundance of the functional metal-nucleotide complex bound to the catalytic site.

Animals↗
PubMed1996

Glycated proteins as indices of glycaemic control in diabetic patients with chronic renal failure.

This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.

Blood Glucose↗
PubMed1996

DNA polymorphisms and linkage disequilibrium in the angiotensinogen gene.

A number of recent studies have implicated the angiotensinogen gene in the aetiology of essential hypertension in Caucasian, Japanese and African Caribbean subjects. We have genotyped 153 healthy white Caucasian subjects at a dinucleotide repeat polymorphism and seven diallelic sites in the coding or flanking regions of the angiotensinogen gene, including one polymorphism not previously studied. We have also documented patterns of linkage disequilibrium between polymorphisms. There is evidence of variation in the frequency of several mutations when compared with published results from other Caucasian control populations, possibly due to cryptic ethnic differences between these groups. This should be considered in the design and interpretation of studies of the angiotensinogen gene.

Adult↗