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Biomedical subjects

A M Carter

Publications and source records attributed to A M Carter.

At least 37 records · Page 2Linked to original sources
PubMed2003

Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease.

P-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells and platelets. A number of polymorphisms in the gene encoding P-selectin have been identified. Objectives were to investigate the relationship of soluble P (sP)-selectin with P-selectin gene polymorphisms and coronary artery disease (CAD). Two hundred and forty-nine patients, with extent of CAD characterized by >or=50% stenosis in one or more coronary arteries, and 252 healthy controls were studied. Soluble P-selectin was significantly higher in the patients than controls after adjustment for age, sex and smoking [patients 49.8 (47.5-52.1) ng mL-1; controls 46.7 (44.5-49.1) ng mL-1, P = 0.03). There was no association of sP-selectin with myocardial infarction (MI) or presence of >or=50% stenosis. The -1817 T/C, -1969 G/A and -2123 C/G (but not the Thr715Pro) polymorphisms were in strong linkage disequilibrium. The Thr715Pro polymorphism was significantly associated with sP-selectin even after adjustment for covariates [TT 48.9 (46.9-50.0) ng mL-1; TP + PP 40.7 (38.1-43.6) ng mL-1, P < 0.0001]. A significant interaction of Thr715Pro and smoking status was identified in the determination of sP-selectin levels. There was no significant association of genotype at any of the polymorphism in relation to MI or stenosis. The Thr715Pro polymorphisms is associated with plasma sP-selectin. This association is modulated by smoking, although the underlying mechanism remains unclear.

Aged↗
PubMed2002

Placentation in the capybara (Hydrochaerus hydrochaeris), Agouti (Dasyprocta aguti) and paca (Agouti paca).

Placentae of three hystricimorph rodents--capybara, agouti and paca--were examined by conventional histology, immunohistochemistry for cytokeratin and vimentin, and TUNEL staining. The placentae were divided into lobules of labyrinthine syncytium separated by interlobular and marginal trophoblast. The subplacenta comprised cytotrophoblasts, supported on lamellae of allantoic mesoderm, and syncytiotrophoblast. The central excavation was still apparent in the definitive placenta of capybara. In agouti and paca, the decidua of the junctional zone formed a mesoplacenta comprising a capsule and a pedicle. Towards term the pedicle formed a tenuous attachment between placenta and uterine wall comprising a few maternal vessels surrounded by degraded tissue. In paca placenta, it was shown by TUNEL staining that breakdown of this tissue occurred by apoptosis. The visceral yolk sac was highly villous and, in agouti, the yolk sac villi were extremely long. Lateral to its attachment to the placenta, the fetal surface was covered with non-vascular yolk sac endoderm. A layer of spongiotrophoblast cells was interposed between the endoderm and the marginal trophoblast.

Animals↗
PubMed2002

Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA.

In the present study, it was hypothesized that the adrenocorticotrophin hormone receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH, as shown for adrenal cortical cells in culture. In chronically catheterized sheep, an intravenous infusion of ACTH(1-24) was given to 6 fetuses for 24 h at a rate of 0.5 microg h(-1), starting on Day 126 or 127 of gestation (term approximately 147 days). Four control fetuses received an infusion of vehicle (saline). Total RNA was extracted from the fetal adrenal glands by the guanidinium thiocyanate method. Expression of specific mRNAs was determined by ribonuclease protection assay using cRNA probes directed against: ACTH-R; the steroid enzymes side-chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17apha-hydroxylase (P450c17) and 21beta-hydroxylase (P450c21); and beta-actin. Ratios of mRNA expression to beta-actin mRNA expression (arbitrary units) were calculated to correct for differences in RNA quality between samples. The concentration (mean +/- SEM) of immunoreactive cortisol in fetal plasma was greater after ACTH infusion than after vehicle infusion (47 +/- 3 v. 13 +/- 2 ng mL(-1) respectively; P<0.001). Adrenal expression of P450scc and P450c21 mRNA increased after ACTH infusion (P<0.05), whereas expression of P450c17 and 3beta-HSD mRNA was unchanged. There was no difference in ACTH-R mRNA expression between ACTH- and vehicle-infused fetuses (254 +/- 48 v. 305 +/- 76 arbitrary units respectively). It was concluded that ACTH is able to increase plasma cortisol concentrations in the sheep fetus by up-regulating cortisol synthesis in the adrenal gland, but that in vivo this does not require up-regulation of ACTH-R mRNA.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Control of growth and development of the feto-placental unit.

Classical gene targeting has identified many genes important for fetal and placental development. Null mutation of these genes may lead to fetal growth restriction, malformation or embryonic death. Growth restriction of epigenetic basis can predispose to adult-onset diseases. The mechanisms underlying this process, termed 'fetal programming', are beginning to be understood.

Animals↗
PubMed2001

Decreased fibrinolytic potential in South Asian women with ischaemic cerebrovascular disease.

To investigate gender differences in conventional, coagulation and fibrinolytic factors in South Asian ischaemic stroke patients, we compared these variables in 50 South Asian females (SAFP) with 90 South Asian males (SAMP) with ischaemic stroke and in 52 females (SAFC) and 38 males (SAMC) without stroke. Plasminogen activator inhibitor-1 (PAI-1) antigen levels were significantly higher in SAFP compared with SAMP (18.2 vs. 13.3 U/ml, P = 0.04) even after adjustment for known covariates, but there was no difference in PAI-1 antigen levels between males and females in the control group. South Asian females exhibited higher levels of factor VII antigen and FVII:C activity in both stroke patients (114 vs. 99% in males, P = 0.01; 116 versus 104% in males, P = 0.04) and controls (116 vs. 97% in males, P = 0.004; 115 vs. 93% in males, P = 0.01). There were no significant differences in the levels of fibrinogen (3.8 vs. 3.7 g/l), FXIIa (2.2 vs. 2.4 ng/ml), von Willebrand factor (1.8 vs. 1.9 IU/ml) and tissue plasminogen activator (11.4 vs. 12.0 ng/ml) in SAMP and SAFP respectively. These results suggest that South Asian females have increased FVII levels and that females with a history of ischaemic stroke have a decreased fibrinolytic potential in comparison with males.

Adult↗
PubMed2001

Evolution of the placenta and fetal membranes seen in the light of molecular phylogenetics.

Recent analyses of nucleotide sequence data suggest that living placental mammals belong to one of four superorders. The early divergence of these groups was followed by long periods of geographical isolation, due to the break up of continental land masses, allowing for convergent evolution of similar traits in different superorders. As an example, the transition from epitheliochorial to haemochorial placentation occurred independently in bats, rodents, anthropoid primates, armadillos and others. A group of ancient African mammals is suggested by the molecular data, but is not fully supported by morphological evidence. The hypothesis is, however, consistent with some of the data on fetal membranes, suggesting that it would be worthwhile to study the early development of tenrecs, golden moles and elephant shrews. Analyses of fetal membrane traits that group the tarsiers with anthropoid primates, and separate them from the lemurs, are challenged by the molecular data. Other relatives of the primates seem to include tree shrews and flying lemurs, and little is known about the fetal membranes of the latter group. Comparative studies of placental function normally are confined to primates, rodents, lagomorphs and domestic animals: the biological diversity represented by mammals that evolved in ancient Africa and South America is not represented. Therefore, future comparative studies should strive to include species such as the rock hyrax and the armadillo.

Animals↗
PubMed2001

To lyse or not to lyse: is it genetic?

The development of cardiovascular disease is influenced by complex interactions between environmental and genetic factors. Despite a flurry of activity in the past decade to identify common genetic variants that predispose to cardiovascular disease the results have, on the whole, been inconclusive. In the present review we summarise the available information regarding genetic variants of fibrinolytic factors and discuss the issues pertinent to understanding the inconsistencies in their reported relationship to cardiovascular disease. Finally, we suggest that work in this area should continue, but with the emphasis firmly directed towards the use of genetic markers as tools for investigating and understanding the complexities of cardiovascular disease.

Blood Circulation↗
PubMed2000

alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism.

The Aalpha-fibrinogen Thr312Ala polymorphism, which occurs in a region involved in factor XIII (FXIII)-dependent cross-linking processes, is associated with poststroke mortality in subjects with atrial fibrillation, suggesting an influence either on intraatrial clot formation or embolization. We have determined the association of Thr312Ala with deep vein thrombosis (DVT) and pulmonary embolism (PE) and have assessed the interaction of Thr312Ala with the FXIII Val34Leu polymorphism in 122 patients with DVT, 99 patients with PE, and 254 healthy control subjects. The genotype distribution of patients with PE (TT = 49%, TA = 36%, AA = 15%), but not DVT (TT = 50%, TA = 42%, AA = 8%), differed significantly from healthy control subjects (TT = 60%, TA = 34%, AA = 6%, P =.02). A significant interaction of Thr312Ala and Val34Leu was also identified (P =.01), indicating an inverse association between Leu34 and Ala312. These results support the hypothesis that Thr312Ala alters FXIII-dependent cross-linking, making formed fibrin clot more susceptible to embolization.

Fibrinogen↗
PubMed2000

Apolipoprotein E polymorphism in cerebrovascular disease.

OBJECTIVES: The aim of this study was to investigate the relationship between the apo E genotype with acute cerebral infarction and primary intracerebral haemorrhage and to examine the relationship of the apo E genotype with mortality following acute stroke. MATERIALS AND METHODS: We studied 592 cases of acute stroke and 289 healthy control subjects clinically free of cerebrovascular disease. Pathological type of stroke was determined by cranial computed tomography and the subtype of cerebral infarction classified according to the Oxfordshire Community Stroke Project Classification (OCSP). Apo E genotype was determined using polymerase chain reaction. RESULTS: There was no difference in apo E genotype frequency between cases and controls (chi2 = 3.58, 5 d.f., P = 0.60). Apo E genotypes were not related to the pathological type of stroke (cerebral infarction, CI, n = 532 and primary intracranial haemorrhage, PICH, n = 60, (chi2 =3.738, 4 d.f., P=0.44) nor with the Oxfordshire Community Stroke Project Classification subtypes of cerebral infarction, lacunar infarction, LACI (n = 169), total anterior circulation infarction, TACI (n = 117), partial anterior circulation infarction, PACI (n = 173), posterior circulation infarction, POCS (n = 54) and including those cerebral infarcts which could not be classified (n= 19), chi2 =31.1, 20 d.f., P=0.153). At the time of the analysis, 243 cases (41.0%) had died. The median follow-up (including death) was 851 days. There was no relationship between time to death and apo E genotype in cases of either CI or PICH. CONCLUSION: In this population, there was no relationship between the apolipoprotein E polymorphism and the pathogenesis of cerebral infarction or primary intracerebral haemorrhage. Apo E genotype was not related to all-cause mortality following stroke.

Aged↗
PubMed2000

Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals.

To better understand the role of the insulin-like growth factors (IGF-I and -II) and their binding proteins (IGFBPs 1-6) in placental development and function, it is important to review similarities and differences between species in expression of the respective mRNAs. In human placenta, IGF-II mRNA is expressed in chorionic mesoderm and first trimester villous cytotrophoblast, but not in syncytiotrophoblast. In contrast, in rhesus monkey placenta, IGF-II mRNA is expressed in syncytiotrophoblast but not in chorionic mesoderm. IGFBP-3 mRNA is present in the chorionic mesoderm of placental villi from both these species and may modulate IGF-II action through a paracrine mechanism. In rodent placentae, IGF-II mRNA is expressed both in fetal mesoderm and in the trophoblast of the placental labyrinth. In guinea pig, where IGFBP-5 mRNA is expressed in the marginal and interlobular syncytium and IGF-II mRNA in the labyrinth, interaction between IGF-II and IGFBP-5 mRNA may be involved in vascularization of the placenta by fetal vessels. In sheep placenta, IGF-II mRNA is expressed, not in the trophoblast layer, but in the fetal mesoderm immediately adjacent to it. In the basal plate of human, rhesus monkey and baboon placentae, extravillous trophoblasts express IGF-II mRNA and uterine decidual cells IGFBP 1-6 mRNAs. The inference is that there is interaction between IGF-II and IGFBPs at the maternal-fetal interface of the primate placenta during trophoblast invasion and decidualization. IGFBP-1 expressed by the decidua may also interact with alpha(5)beta(1)integrin expressed by the extravillous trophoblast. The placentae of rodents are also of the invasive type. Glycogen cells of the mouse placenta are analogous with human extravillous trophoblast and express IGF-II mRNA. However, expression of IGFBP mRNAs in the mouse, as in the guinea pig, is confined to non-decidualized endometrium and myometrium. IGF-II mRNA is strongly expressed by trophoblasts invading uterine vessels in human and guinea pig placentae. Interactions probably occur between IGF-II expressed by these trophoblasts and IGFBPs expressed in the vessel walls. However, it is possible that IGFBPs expressed by maternal vessels are associated with processes that are independent of trophoblast invasion. Thus, IGFBP-3 mRNA is highly expressed in the maternal blood vessels of the non-deciduate sheep placenta. Findings to date highlight the diversity in the expression of the IGF system among placentae of man and different laboratory animals, and even between closely related species. Comparative studies will continue to be required to understand the functional role of IGFs and IGFBPs in each species.

Animals↗
PubMed1999

Association of the alpha-fibrinogen Thr312Ala polymorphism with poststroke mortality in subjects with atrial fibrillation.

BACKGROUND: The alpha-fibrinogen Thr312Ala polymorphism occurs in close proximity to several sites important for factor XIIIa-dependent cross-linking, which raises the possibility that it affects fibrin clot stability. METHODS AND RESULTS: We determined the association of this polymorphism with ischemic stroke, stroke subtype, and poststroke mortality. There was no significant difference in the genotype distributions of patients with acute ischemic stroke (n=519) and healthy control subjects (n=423), nor was there any association of this polymorphism with stroke subtype. In a Cox regression model, a significant interaction between Thr312Ala and atrial fibrillation was identified in relation to poststroke mortality (P=0.002). In subjects in sinus rhythm (n=418), there was no difference according to genotype in the proportion of subjects who survived (approximately 60% in each group), whereas in subjects with atrial fibrillation (n=101), there was decreased survival in those possessing the A allele (TT=42.1%, TA=18%, AA=0%). CONCLUSIONS: The Thr312Ala polymorphism may give rise to an increased susceptibility for embolization of intra-atrial clot, and these findings could have important implications for identifying subjects most at risk of developing thromboembolic complications.

Amino Acid Substitution↗
PubMed1999

Ontogeny of expression of insulin-like growth factor (IGF) and IGF binding protein mRNAs in the guinea-pig placenta and uterus.

To determine the temporal and spatial distribution of insulin-like growth factor (IGF) and its family of binding proteins (IGFBPs), guinea-pig yolk sac and chorioallantoic placentae were collected at 15, 20, 25, 29, 44-45, 55 and 65-66 days of gestation. Messenger RNAs for IGF I, IGF II and IGFBP 1-6 were identified in tissue sections by in situ hybridization, using 35S-cRNA probes. Epithelial and mesenchymal cell types were identified by immunohistochemistry for cytokeratin and vimentin, respectively. At 15 days of gestation, IGF-II mRNA was expressed in ectoplacental mesoderm, cytotrophoblasts and syncytiotrophoblast, and IGFBP-5 mRNA was detected in the syncytiotrophoblast. In the mid-gestation placenta, IGFBP-5 mRNA was expressed in the marginal and interlobular syncytium and IGF-II mRNA in the labyrinth. Near term, when expansion of the labyrinth was complete, IGFBP-5 mRNA was coexpressed with IGF-II mRNA in the marginal and interlobular syncytium. These observations suggest that interaction between IGF-II and IGFBP-5 plays a role in the vascularization of the placenta by fetal vessels. IGF-II mRNA was not expressed in the maternal tissues at any gestational age. IGFBP-2, -3 and -5 mRNAs were expressed in the endometrial stroma at 7-12 days of gestation but, following establishment of the placenta, IGFBP mRNAs were more abundant in the myometrium than in the decidua. IGF-II mRNA was detected in trophoblasts invading the walls of maternal vessels, and the endothelium of the preplacental vessels expressed IGFBP-4 mRNA, while IGFBP-2 and IGFBP-5 mRNAs were present in the tunica media of mesometrial arteries that had not been invaded by trophoblast. These findings suggest that IGF-II produced by the trophoblast acts in an autocrine and/or paracrine fashion to promote trophoblast invasion and that this process is modulated by interaction with IGFBPs present in maternal tissues.

Animals↗