Platelet glycoprotein IIIa PlA polymorphism in young men with myocardial infarction.
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Adult↗
Biomedical subjects
A M Carter
Publications and source records attributed to A M Carter.
Catecholamine and serotonin concentrations in fetal guinea-pig brain: relation to regional cerebral blood flow and oxygen delivery in the growth-restricted fetus.
To test the hypothesis that intrauterine growth restriction (IUGR) would lead to altered neurotransmitter metabolism in the brain because of poorer oxygenation, blood flows and tissue concentrations of noradrenaline, dopamine, serotonin and their metabolites were measured in 14 parts of the brain of guinea-pig fetuses at 61-64 days' gestation. Eight fetuses with IUGR induced by uterine artery ligation were compared with 8 controls. Regional brain blood flows were determined by the microsphere method and tissue concentrations of monoamines by HPLC with electrochemical detection. The oxygen content of preductal arterial blood was significantly lower in IUGR fetuses than in controls (2.3 +/- 0.6 v. 3.5 +/- 0.5 mM; P < 0.001). Although this was compensated by increases in blood flow to many areas of the brain, significant decreases occurred in oxygen delivery to the temporal and occipital cortex, hippocampus and cerebellum of IUGR fetuses. In contrast, oxygen delivery to brainstem areas was maintained. Noradrenaline concentrations were closely similar in brains from the two groups, except for an increase in the caudate nucleus of IUGR fetuses. Dopamine concentrations were significantly elevated in brainstem areas. Concentrations of 3,4-dihydroxyphenylglycol (DOPEG), a noradrenaline metabolite, and 3,4-dihydroxyphenylacetic acid (DOPAC), a dopamine metabolite, showed a similar pattern of increase in brains of IUGR fetuses, possibly resulting from increased synthesis of noradrenaline and dopamine rather than from decreased degradation. Concentrations of serotonin were significantly higher in frontal and temporal cortex of IUGR fetuses, and the serotonin metabolite 5-HIAA increased significantly in cortical areas. Changes in neurotransmitter metabolism could not be related to oxygen supply, since serotonin concentrations increased in the forebrain, despite reduced oxygen delivery and the known dependence of tryptophan-5-hydroxylase on tissue PO2, and dopamine levels were elevated in the brainstem, where the oxygen supply was maintained.
Animals↗
The influence of Helicobacter pylori status on circulating levels of the coagulation factors fibrinogen, von Willebrand factor, factor VII, and factor VIII.
BACKGROUND: Helicobacter pylori (H. pylori) infection has been associated with an increased risk of developing ischemic heart disease (IHD). It has been suggested that a persisting low-grade acute phase response results from the chronic inflammation caused by H. pylori infection, which may give rise to increased circulating levels of certain coagulation factors. MATERIALS AND METHODS: One hundred three (53 male) nonconsecutive, randomly selected white subjects with symptoms of dyspepsia were recruited for study from an outpatient endoscopy clinic at Leeds General Infirmary. The presence of H. pylori was determined by histological and microbiological investigation, a rapid urease test, and a 13carbon urea breath test (13C-UBT). Fibrinogen was measured by the Clauss method, factor VIII:C (FVIII:C) and factor VII:C (FVII:C) were measured by clotting rate assays, and the von Willebrand factor (vWF) was determined by an enzyme-linked immunosorbent assay. RESULTS: No difference was found in levels of coagulation factors according to H. pylori status. Multiple regression models were used to account for the effect of covariates and H. pylori status on levels of FVII:C, FVIII:C, vWF, and fibrinogen, and again H. pylori status was not a significant determinant of levels of any of these coagulation factors. No difference occurred in full blood count, platelet count, white cell count, or plasma viscosity in individuals who were H. pylori-positive compared with those who were negative. CONCLUSIONS: H. pylori infection is not associated with increased circulating levels of fibrinogen, FVII:C, vWF.Ag, or FVIII:C or hemorrheology in this patient group.
Adult↗
Effect of fetal growth restriction on system A amino acid transporter activity in the maternal facing plasma membrane of rat syncytiotrophoblast.
To determine whether reduced maternofetal transfer of neutral amino acids in growth-restricted fetal rats is due to decreased system A transporter activity, we measured Na(+)-dependent MeAIB uptake by membrane vesicles from placentas of fetuses growth-restricted due to uterine artery ligation and control placentas (sham ligation). Na(+)-dependent uptake of methylamino-isobutyric acid (MeAIB) was linear over 15-60 s in vesicles from both ligated and sham-ligated sides of the uterus. Na(+)-dependent uptake of MeAIB at 30 s did not differ in paired measurements on vesicles from ligated and sham-ligated horns, 0.063 +/- 0.004 versus 0.056 +/- 0.005 nmol/mg of vesicle protein. The kinetics of Na(+)-dependent MeAIB uptake were similar in paired measurements on vesicles from ligated and sham-ligated horns, with overall K(m) = 4.4 +/- 0.5 mM and Vmax = 0.93 +/- 0.08 nmol/mg vesicle protein per 30 s. Uptake of tracer was inhibited 85-95% by known substrates for the system A amino acid transporter (alanine > or = serine > MeAIB > glycine = proline). We conclude that the system A transporter is present in the maternal facing plasma membrane of rat syncytiotrophoblast, but that the activity of this system, per mg of vesicle protein, is unaffected in fetal growth restriction induced by a decrease in maternal placental blood flow in late pregnancy.
Amino Acids↗
Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep.
To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic-pituitary-adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 microns microspheres for 8 days from about day 124 of gestation (term approximately 147 days) and sham-embolized controls. Starting before the final embolization (or sham-embolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1-24 (0.5 microgram/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 +/ 15 vs 292 +/- 25 ml/min per 100 g tissue; mean +/- S.E.; P<0.01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and sham-embolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0.05) due to decreased vascular resistance (P<0.01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.
Adrenal Glands↗
Beta-fibrinogen gene-455 G/A polymorphism and fibrinogen levels. Risk factors for coronary artery disease in subjects with NIDDM.
OBJECTIVE: To investigate the association of a G/A polymorphism at position -455 of the beta-fibrinogen gene and fibrinogen levels in the development of coronary artery disease (CAD) in subjects with NIDDM. RESEARCH DESIGN AND METHODS: In 187 Caucasian subjects with NIDDM, presence of CAD was taken as a clinical history of angina, myocardial infarction, coronary angioplasty, or coronary artery bypass grafting, confirmed from medical case notes. RESULTS: Fibrinogen levels were significantly higher in subjects with CAD (n = 38, 3.41 [3.12-3.73] g/l) than those without (n = 149, 2.99 [2.87-3.11] g/l, P = 0.004 [geometric mean, 95% CI]). Comparing the genotype frequencies by chi 2 testing, there was a significant difference between subjects with CAD (GG = 0.84, GA + AA = 0.16) and those without (GG = 0.64, GA + AA = 0.36, P = 0.02). In a logistic regression model, including age, BMI, cholesterol, sex, smoking, triglycerides, and plasminogen activator inhibitor antigen as covariates, genotype and fibrinogen levels were significantly associated with CAD. The odds ratio for having CAD in individuals homozygous for the G allele compared with those possessing the A allele was 1.77 (1.08-2.90), P = 0.03; and for an increase of 1 g/l in fibrinogen levels was 1.60 (1.00-2.60), P = 0.05. CONCLUSIONS: These data suggest a relationship between the -455 G/A beta-fibrinogen gene polymorphism and the development of CAD in subjects with NIDDM. This relationship was not associated with variations in fibrinogen levels, suggesting that this polymorphism may be in linkage with a polymorphism within the coding region of the beta-fibrinogen gene, which results in an alteration in the stability of the fibrin clot.
Adenine↗
Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease.
BACKGROUND AND PURPOSE: There is evidence that an allelic variation in the angiotensin-converting enzyme (ACE) gene may confer an increased risk of vascular disease. The roles of the ACE insertion/deletion polymorphism and circulating ACE levels are unknown in cerebrovascular disease. METHODS: We studied an insertion/deletion polymorphism within intron 16 of the ACE gene by polymerase chain reaction and plasma ACE activity in 467 cases of stroke, the pathological type of which was established by cranial CT, and 231 control subjects. ACE genotype and activity were related to stroke type and mortality at 4 weeks and 3 months. RESULTS: No difference in genotype frequency was observed between all subjects with stroke and control subjects or between control subjects and subjects with cerebral infarction or cerebral hemorrhage. Plasma ACE activity was significantly lower in stroke patients at presentation (64.1 IU/L) than in control subjects (79.6 IU/L; P<.0001). Twenty-one patients (4.5%) with cerebral infarction died within 4 weeks and 56 patients (12%) within 3 months. These patients had significantly lower plasma ACE activity than patients who survived. There was some evidence that risk of death within 4 weeks increased with the number of D alleles (P=.02). Among survivors, plasma ACE activity showed a mean increase of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels at presentation and at 3 months (73.6 IU/L), the latter being similar to ACE activity in control subjects. CONCLUSIONS: Low ACE activity at sroke presentation and possession of the D allele may be associated with increased risk of early death from acute cerebral infarction.
Adult↗
Conference report: the Fourth International Conference on Veterinary Perinatology, Churchill College, Cambridge, 7-9 July 1995.
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Perinatology↗
Effect of arginine vasopressin on regional adrenal blood flow and plasma cortisol concentration in fetal sheep.
OBJECTIVE: To determine whether arginine vasopressin (AVP) at plasma concentrations measured during moderate hypoxemia affects adrenal blood flow. STUDY DESIGN: Regional blood flows were measured in 5 unanesthetized normoxemic fetuses (124-128 days' gestation) during a 24-h intravenous infusion of AVP in isotonic saline solution. Another 5 fetuses received an infusion of vehicle. Blood flows were determined before the infusion and at 2 h and 24 h from its onset using radionuclide-labeled microspheres. RESULTS: At 2 h and 24 h of AVP infusion, fetal plasma concentrations of IR-AVP had risen from 4.7 +/- 0.9 pg/ml to 9.8 +/- 1.1 pg/l and 9.4 +/- 0.7 pg/ml, respectively. Thus we achieved plasma concentrations of IR-AVP comparable to those previously reported during moderate hypoxemia. There was no significant effect of treatment on fetal plasma concentrations of immunoreactive adrenocorticotropic hormone (ACTH) or cortisol. AVP infusion significantly decreased fetal heart rate and raised cotyledonary blood flow from 198 +/- 18 ml/min per 100 g to 235 +/- 17 ml/min and 218 +/- 10 ml/min per 100 g at 2 h and 24 h, respectively, from the start of the AVP infusion. Basal values for adrenal medullary and cortical blood flows were similar in the AVP and saline groups, and did not change significantly during the infusions. CONCLUSION: These findings suggest that the rise in adrenal blood flow seen after hypoxemia is not due to a direct action of systemic AVP, but is attributable to other influences, likely including changes in circulating ACTH.
Adrenal Glands↗
Local transfer of hormones between blood vessels within the adrenal gland may explain the functional interaction between the adrenal cortex and medulla.
The adrenal cortex has a local stimulatory action on synthesis and secretion of adrenaline by the adrenal medulla. This interaction may be based on nervous transmission and/or on glucocorticoids secreted trom the cortex either exerting paracrine effects or reaching the medulla through the local vascular system. The existence of a dual capillary network, a portal system, now seems unlikely. However, a new concept is postulated: the high demand for glucocorticoids in the medulla may be met by local transfer to blood vessels within the adrenal gland, particularly the medullary arteries.
Adrenal Cortex↗
Control of placental blood flow: workshop report.
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Animals↗
Inhibition of ACTH secretion blocks hypoxia-induced increase of adrenal cortical blood flow in fetal sheep.
To examine the role of endogenous adrenocorticotropic hormone (ACTH) in adrenal blood flow responses to hypoxia, we studied unanesthetized ovine fetuses during an intravenous infusion of cortisol or vehicle. Fetal hypoxia was induced after 5 h of cortisol or vehicle infusion. Control fetuses were not made hypoxic. Blood flows were determined before and at three time points during the infusions. At 2 and 6 h of hypoxia, in vehicle-infused fetuses, fetal plasma concentrations of immunoreactive ACTH (irACTH) had risen from 9 +/- 3 (SE) pg/ml to 68 +/- 25 and 127 +/- 37 pg/ml, respectively. No significant change in fetal plasma irACTH occurred in the other groups. Adrenal cortical blood flow rose three- to fourfold during hypoxia in vehicle-infused fetuses but did not change from prehypoxia levels in cortisol-infused fetuses (P < 0.005). Medullary flow rose with hypoxemia, and this was not affected by concurrent cortisol infusion. Adrenal blood flows did not change in the control groups. Thus prior infusion of cortisol suppressed the rise in fetal plasma ACTH during hypoxia and selectively blocked the increase in adrenal cortical blood flow.
Adrenal Cortex↗
CHAMPUS psychiatric inpatient savings: military management versus contractor, the Fort Polk experience.
Inpatient psychiatric costs were a significant part of the CHAMPUS bill at Bayne Jones Army Community Hospital. With implementation of Gateway to Care, a case management program was developed for intervention. In May 1993, Foundation Health Federal Services Inc. began a modified CHAMPUS Reform Initiative program providing an opportunity to retrospectively analyze two methods of managed care. Civilian hospital inpatient admissions for both programs during fiscal year (FY) 1993 were compared to corresponding periods in FY 1992. Under the case management program, admissions were reduced by 67%, occupied bed days by 74%, and costs by 76%. Under the Foundation Health Program, admissions were reduced by 13%, occupied bed days by 15%, and total costs by 42%. Both methods achieved savings over standard CHAMPUS. In spite of constraints that Foundation Health did not have, the case management program appeared to be more effective, demonstrating that a managed health care program directed by the hospital commander can significantly reduce costs.
Contract Services↗
Regulation of insulin-like growth factor-II gene expression in the ovine fetal adrenal gland by adrenocorticotropic hormone and cortisol.
Maturation and activation of the fetal adrenal gland is crucial to fetal organ maturation and the onset of parturition in sheep. Insulin-like growth factors (IGFs) have been demonstrated to promote fetal adrenal mitogenesis and steroidogenesis in some species. Our previous studies showed that IGF-II mRNA is expressed in the steroidogenic cells of the fetal sheep adrenal, suggesting that IGF-II may be an important regulator of fetal adrenal function. However, the regulation of IGF-II gene expression is poorly understood. In the present study we measured the changes in IGF-II mRNA level in fetal sheep adrenals during late gestation in response to ACTH and cortisol. Either saline (0.5 ml/h) or cortisol (1 mg/24 h) was infused for 100 h to fetal sheep beginning on day 95 or 96 of pregnancy, or saline (0.5 ml/h), ACTH (0.5 micrograms/h) or cortisol (1 mg/h) was infused for 84 h to fetal sheep beginning on days 120-125 of pregnancy (term = 145 days). Adrenal RNA was subjected to Northern blot analysis with an ovine IGF-II cDNA probe. The relative abundance of total IGF-II mRNA decreased significantly in the ACTH- and cortisol-treated fetuses. IGF-II mRNA was localized by in situ hybridization using a 35S-labeled antisense ovine IGF-II cRNA probe, and IGF-II peptide was localized by immunohistochemistry. There were no differences in the cellular distribution patterns of IGF-II mRNA and IGF-II peptide after treatments, but the intensity of the hybridization signal for IGF-II mRNA and of immunostaining for IGF-II peptide decreased in adrenals from fetuses treated with ACTH or cortisol. These results suggest that ACTH and cortisol decrease IGF-II gene expression in the ovine fetal adrenal. We speculate that the cortisol surge observed in the late gestation ovine fetus may be responsible for down-regulation of IGF-II gene expression in the fetal adrenal at or just before birth.
Adrenal Glands↗
Polymorphisms of the plasminogen activator inhibitor-1 gene in type 1 and type 2 diabetes, and in patients with diabetic retinopathy.
To identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subjects (192 type 1, 327 type 2) and 123 Caucasian control subjects there were no differences in the frequency of the Hind III restriction alleles (type 1 vs type 2 vs control: allele 1 0.397 vs 0.420 vs 0.448; allele 2 0.603 vs 0.580 vs 0.552) nor in the allelic frequency at either dinucleotide repeat sequence. In 86 subjects with no retinopathy at 15 years or more from diagnosis of diabetes and 190 subjects with diabetic retinopathy there was no difference in the frequency of Hind III restriction alleles (retinopathy present vs retinopathy absent: allele 1 0.400 vs 0.467; allele 2 0.600 vs 0.533) nor in the allelic frequencies at either dinucleotide repeat sequence. The results indicate that there is no or minimal influence of the PAI-1 gene on either PAI-1 levels or the development of diabetic retinopathy in patients with diabetes mellitus.
Adolescent↗
Regional adrenal blood flow responses to adrenocorticotropic hormone in fetal sheep.
To determine whether adrenocorticotropic hormone (ACTH) at plasma concentrations measured during mild hypoxemia and at term affects adrenal blood flow, we measured regional blood flows in five unanesthetized normoxemic fetuses (125-130 days gestation) during a 24-h intravenous infusion of ACTH-(1-24) in isotonic saline solution. Another five fetuses received an infusion of vehicle. Blood flows were determined before the infusion, at 2 and 24 h from its onset, and 24 h afterward using radionuclide-labeled microspheres. Blood flow to the adrenal medulla was fivefold greater than that to the adrenal cortex. Adrenal blood flow rose 99% at 24 h of the ACTH infusion. There was a large increase in adrenal cortical blood flow of 272% at this time but medullary blood flow did not change significantly during ACTH infusion. The rise in cortical blood flow was attributable to decreased vascular resistance. No significant alterations occurred in fetal arterial blood pressure and heart rate, or in blood flow to other lower body organs of the fetus or to the placental cotyledons. These findings are consistent with the hypothesis that the increase in adrenal blood flow observed during fetal hypoxia is associated with changes in plasma ACTH concentration. They are also indicative of selective regulation of cortical and medullary blood flows in the sheep fetus at this stage of gestation.
Adrenal Cortex↗
The metabolism of free fatty acids and triacylglycerols by the fetal liver in a guinea pig model of intrauterine growth retardation.
The aim of this study was to determine whether intrauterine growth retardation (IUGR) is associated with an alteration in hepatic lipid metabolism. IUGR was induced in 25 guinea pigs by uterine artery ligation on gestational d 30. On d 62, after anesthesia, an infusion of [1-14C]-palmitic acid was given. Fetuses were exposed at 15, 30, and 45 min, and simultaneous maternal and umbilical venous blood samples were taken. Livers were divided into right lobe, right and left sublobes of the quadrate lobe, and left lobe. In control fetuses, plasma radiolipids rose in parallel with, but were about half the value of, maternal levels. In IUGR fetuses, plasma radiolipids were lower than in controls at 15 and 30 min but were comparable at 45 min. Most of the radiolipid in the maternal plasma was FFA, with only 6% incorporated into triglycerides at 45 min. In control and IUGR fetal plasmas, 36-37% of the radiolipid was triglycerides by 45 min. Radiolabel incorporation into the right lobe was less than into the left lobe and left half of the quadrate lobe in control and IUGR fetuses. Compared with controls, radiolabel incorporation in IUGR fetuses was less in some or all liver lobes at each time point. The proportion of label associated with FFA and triglycerides did not vary with time, between lobes, or between control and IUGR fetuses. The difference in uptake between lobes reflects their blood supply, implying that most FFA is extracted during the first passage of the umbilical venous blood. Growth retardation was not associated with compromised hepatic FFA metabolism.
Animals↗
Gastrin releasing peptide immunoreactivity is present in ovine amniotic fluid and fetal and maternal circulations. MRC Group in Fetal and Neonatal Health and Development.
Using antisera directed towards the C-terminal region of gastrin releasing peptide (GRP), significant quantities of GRP-like immunoreactivity (GRPLI) were detected in ovine amniotic fluid and in the fetal and maternal circulations. The highest GRPLI levels were found in amniotic fluid (2135 +/- 829 fmol/ml, n = 12; mean +/- SEM), followed by those in ovine fetal (604 +/- 267 fmol/ml, n = 13) and maternal plasma (229 +/- 89 fmol/ml, n = 13). On gel filtration chromatography, the predominant GRPLI form in each fluid eluted in an identical position consistent with the entity being of apparently larger molecular size than porcine GRP1-27. Certain fetal plasma samples contained a second GRPLI peak eluting at the void volume. Hence, during ovine pregnancy a GRPLI entity circulates in fetal and maternal plasma; the entity is of apparently larger molecular size than GRP1-27 but contains a structure immunologically indistinguishable from the bioactive c-terminal region of GRP1-27. Given the recognized bioactivities of GRP, this entity may be an important hormone during ovine fetal life.
Amniotic Fluid↗