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Biomedical subjects

M A Hanson

Publications and source records attributed to M A Hanson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Circulatory responses to maternal hyperoxaemia and hypoxaemia assessed non-invasively in fetal sheep at 0.3-0.5 gestation in acute experiments.

OBJECTIVES: To determine fetal haemodynamic responses to hyperoxaemia and hypoxaemia in early pregnancy. DESIGN: Repeated measurements in acute experiments. SETTING: Experimental physiology laboratory. METHODS: Non-invasive Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common carotid arteries of 12 fetal lambs (0.27-0.56 gestation) during maternal hyperoxaemia and hypoxaemia under ketamine anaesthesia. The effect of gestational age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for dependent measurements and P < or = 0.05 was considered significant. Differences between groups were considered significant if the 95% confidence interval did not include zero. RESULTS: Gestational age had a significant effect on the blood velocity in the umbilical vein and ductus venosus. There were no circulatory changes during hyperoxaemia, but a simultaneous increase of pCO2 was an important confounder. However, hypoxaemia caused significantly reduced heart rate, reduced maximum and weighted mean blood velocity, and augmented pulsation in the umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus (peak velocity during systole and minimum during diastole, and time-averaged velocity) and augmented pulsation of the flow velocity. Additionally, the pulsatility of blood flow increased in the umbilical artery and was reduced in the common carotid artery. CONCLUSIONS: Maternal hypoxaemia in early pregnancy causes similar fetal circulatory responses to those in late pregnancy: bradycardia, reduced venous flow velocities, augmented pulsatility in veins and a redistributional flow velocity pattern of the umbilical and common carotid arteries.

Animals↗
PubMed2001

Adenosine produces changes in cerebral hemodynamics and metabolism as assessed by near-infrared spectroscopy in late-gestation fetal sheep in utero.

Rises in fetal adenosine during hypoxia may have a metabolic inhibitory role that helps the fetus adapt to periods of low arterial partial pressure of oxygen (P(a)O(2)). We examined the fetal cerebral hemodynamic and metabolic responses to exogenous adenosine infusion and compared this with previous studies. Six fetal sheep at ca. 125 d gestation were instrumented under general anesthesia with catheters, flow probes, and near-infrared optodes and allowed to recover. After 3 d, adenosine was infused at a level known to reproduce fetal levels during hypoxia. Fetal hemodynamics and cerebral near-infrared spectroscopic (NIRS) variables were monitored and paired blood samples taken for oxygen delivery and consumption calculation. Fetal heart rate, mean arterial pressure, and carotid flow showed no change during adenosine infusion. Cerebral oxyhemoglobin (HbO(2)), deoxyhemoglobin (Hb), and blood volume rose, suggesting venous pooling in the brain. Cerebral cytochrome oxidase (CcO) became more oxidized, indicating reduction in electron flow down the mitochondrial electron transfer chain and, thus, a fall in metabolic rate. Blood sample analysis revealed that there was no change in oxygen delivery to the head but that cerebral oxygen consumption fell during adenosine infusion. These data indicate that fetal cerebral metabolism fell during infusion of adenosine at a level known to reproduce fetal plasma concentrations during hypoxia.

Adenosine↗
PubMed2001

Mild maternal undernutrition in the first half of ovine pregnancy influences placental morphology but not fetal Doppler flow velocity waveforms and fetal heart size.

AIMS: We wanted to investigate whether experimental dietary manipulations during early pregnancy influence placental growth and subsequently the cardiovascular system as assessed non-invasively by ultrasonography in the sheep fetus. METHODS: 21 ewes bearing singletons of uniform age were randomly assigned for the first half of pregnancy to one of the following study groups: fed 100% of their nutritional requirements (i.e. controls), global reduction in total intake by 30% (i.e. 70% global) and reduction in protein intake by 30% (i.e. 70% protein). RESULTS: Placentas from the 70% protein group had significantly more small placentomes, but significantly fewer large placentomes compared to the 70% global group. However, there were no significant differences between the three dietary groups for either the aortic or the umbilical Doppler velocimetry parameters and the fetal heart rate or heart size. CONCLUSIONS: The present study shows that early mild maternal undernutrition produces subtle changes in cotelydonary weight. However, Doppler and echocardiographic parameters were not affected by these changes.

Animals↗
PubMed2000

Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement.

Antibody AZ-28 was generated against the chairlike transition-state analogue (TSA) 1 and catalyzes the oxy-Cope rearrangement of substrate 2 to product 3. The germline precursor to AZ-28 catalyzes the reaction with a 35-fold higher rate (k(cat)/k(uncat) = 163 000), despite a 40-fold lower binding affinity for TSA.1 (K(D) = 670 nM). To determine the structural basis for the differences in the binding and catalytic properties of the germline and affinity-matured antibodies, the X-ray crystal structures of the unliganded and TSA.1 complex of antibody AZ-28 have been determined at 2.8 and 2.6 A resolution, respectively; the structures of the unliganded and TSA.1 complex of the germline precursor to AZ-28 were both determined at 2. 0 A resolution. In the affinity-matured antibody.hapten complex the TSA is fixed in a catalytically unfavorable conformation by a combination of van der Waals and hydrogen-bonding interactions. The 2- and 5-phenyl substituents of TSA.1 are almost perpendicular to the cyclohexyl ring, leading to decreased orbital overlap and decreased stabilization of the putative transition state. The active site of the germline antibody appears to have an increased degree of flexibility-CDRH3 moves 4.9 A outward from the active site upon binding of TSA.1. We suggest that this conformational flexibility in the germline antibody, which results in a lower binding affinity for TSA.1, allows dynamic changes in the dihedral angle of the 2-phenyl substituent along the reaction coordinate. These conformational changes in turn lead to enhanced orbital overlap and increased catalytic rate. These studies suggest that protein and substrate dynamics play a key role in this antibody-catalyzed reaction.

Antibodies, Catalytic↗
PubMed2000

Effects of hypoxia on plasma amino acids of fetal sheep.

Secondary amino acid disturbances from circulatory responses during hypoxia may cause problems in interpreting plasma amino acid profiles of sick babies investigated for possible inherited defects. Systematic studies to characterise them are difficult in man. We investigated the effects of hypoxia on plasma amino acids by studying 9 late gestation fetal sheep in utero during 11 one hour episodes of moderately severe isocapnic hypoxia. In 6 experiments, maternal plasma amino acids were also monitored. Fourteen fetal plasma amino acids increased significantly, with the largest proportionate changes in alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, ornithine and lysine. Maternal amino acids did not increase. Probable explanations were reflex peripheral vasoconstriction in skeletal muscle beds and decreased hepatic blood flow. The findings extend our knowledge of the fetal response to hypoxic stress, demonstrate the importance of skeletal muscle in branched-chain amino acid metabolism, and should help with interpretation of postnatal plasma amino acid disturbances.

Amino Acids↗
PubMed2000

Simultaneous use of two ultrasound scanners for motion-gated three-dimensional fetal echocardiography.

The aim of this study was to determine whether or not simultaneous use of an additional Doppler transducer could provide sufficient cardiovascular motion information without significantly interfering with three-dimensional (3-D) cardiac structural data acquisition by a primary two-dimensional (2-D) transducer. To determine sources of interference, paired transducers were activated alternatively and simultaneously in and out of a water bath, with and without electrical insulating and electromagnetic shielding. To determine factors affecting interference, pairs were tested on a phantom with different separating distances and angles between paired ultrasound (US) beams and under different 2-D depths and Doppler scales. Results show that the dominant source of interference is acoustic cross talk. The severity was mainly affected by transducer pairing and by separating distances and angles, and the pattern by display settings. With optimised settings, sufficient structural and motion data were obtained simultaneously in 9 of 12 fetal hearts, and detailed 3-D views could be reconstructed free of motion artefacts, confirming the feasibility of using the method for motion-gated 3-D fetal cardiac imaging. New scanner design strategy was then proposed.

Artifacts↗
PubMed2000

Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution.

Botulinum neurotoxin serotype B is a zinc protease that disrupts neurotransmitter release by cleaving synaptobrevin-II (Sb2), one of three SNARE proteins involved in neuronal synaptic vesicle fusion. The three-dimensional crystal structure of the apo botulinum neurotoxin serotype B catalytic domain (BoNT/B-LC) has been determined to 2.2 A resolution, and the complex of cleaved Sb2 with the catalytic domain (Sb2-BoNT/B-LC) has been determined to 2.0 A resolution. A comparison of the holotoxin catalytic domain and the isolated BoNT/B-LC structure shows a rearrangement of three active site loops. This rearrangement exposes the BoNT/B active site. The Sb2-BoNT/B-LC structure illustrates two distinct binding regions, which explains the specificity of each botulinum neurotoxin for its synaptic vesicle protein. This observation provides an explanation for the proposed cooperativity between binding of full-length substrate and catalysis and suggest a mechanism of synaptobrevin proteolysis employed by the clostridial neurotoxins.

Amino Acid Sequence↗
PubMed2000

Amniotic gas values and acid-base status during acute maternal hyperoxemia and hypoxemia in the early fetal sheep.

OBJECTIVE: This study was undertaken to determine amniotic fluid gas values and acid-base balance during maternal hyperoxemia and hypoxemia in early pregnancy. STUDY DESIGN: Anesthetized sheep (n = 12) in early and mid pregnancy (0.3 to 0.5 gestation) were subjected to hyperoxemia followed by hypoxemia. Amniotic fluid PO (2), pH, PCO (2), bicarbonate concentration, and base excess were monitored continuously with a multiparameter Paratrend (Diametrics Medical Inc, St Paul, Minn) sensor and compared between 0.3 and 0.5 gestation. RESULTS: During maternal normoxemia all parameters were constant. At all gestational ages maternal hyperoxemia caused no changes apart from a rapid increase in amniotic fluid PO (2) (P <.001). Maternal hypoxemia led to a reduced amniotic fluid PO (2) (P <.001), whereas the PCO (2) and the bicarbonate concentration increased (P <.001). Changes in amniotic fluid gas values and acid-base balance were more pronounced at 0.3 gestation than at 0.5 gestation. Amniotic fluid Po(2) responded earlier to maternal hyperoxemia than to hypoxemia (9. 5 vs 14.3 minutes; P <.001). During hypoxemia maternal PaCO (2) changed faster than did amniotic fluid PCO (2) (P <.001). CONCLUSIONS: Acute maternal hypoxemia during early pregnancy was quickly reflected in amniotic fluid gas values and acid-base balance, whereas hyperoxygenation induced the quickest changes in amniotic fluid PO (2). The metabolic effects of maternal hyperoxemia and hypoxemia were also more pronounced during early pregnancy than at mid pregnancy.

Amniotic Fluid↗
PubMed2000

Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep.

OBJECTIVE: The aim of this study was to investigate functional development of small arteries from the skeletal circulation of fetal sheep and to determine whether maternal undernutrition affects responses to vasoconstrictive and vasodilatory agonists in arteries from the late-gestation fetus. STUDY DESIGN: We investigated vasoconstrictive and vasodilatory responses of isolated small (approximately 300 microm) arteries from the femoral vascular bed of fetal sheep and from late-gestation pregnant ewes. Ewes were fed either 100% of the nutritional requirement throughout pregnancy (control group) or a restricted diet of 85% or 50% of the nutritional requirement for the first 70 days of pregnancy. For the remainder of pregnancy all ewes were fed the complete diet. RESULTS: Among control group animals vasoconstriction in response to norepinephrine was well developed in fetuses at 0.6 and 0.9 gestation with respect to that in the ewes. When expressed as a percentage of the response to 125-mmol/L potassium (to correct for differences in vessel size and muscle mass), maximum constriction in response to norepinephrine was greater in fetal vessels from 0.9 gestation than in either those at 0.6 gestation or those of the ewes. Endothelium-dependent vasorelaxation responses to acetylcholine and bradykinin were also well developed in fetuses at 0.6 and 0.9 gestation and were similar to those in the ewes. In fetuses at 0.9 gestation the 50% nutritional restriction of the ewe led to blunted endothelium-dependent vasodilatation in response to acetylcholine and blunted endothelium-independent vasodilatation in response to sodium nitroprusside. Responses in the fetuses at 0.9 gestation in which the ewes were fed a restricted diet of 85% were normal. CONCLUSION: This study shows that from midgestation onward small arteries from the skeletal circulation of the fetal sheep have the functional capacity to respond to norepinephrine and endothelium-dependent vasodilators (eg, acetylcholine and bradykinin). The blunted responses to acetylcholine and sodium nitroprusside in the fetuses at 0.9 gestation among the group of dietarily restricted ewes (restricted diet of 50% group) were indicative of impaired vascular smooth muscle sensitivity to nitric oxide. This defect may contribute to the development of hypertension in later life.

Acetylcholine↗
PubMed2000

Effect of maternal nutrient restriction in early gestation on responses of the hypothalamic-pituitary-adrenal axis to acute isocapnic hypoxaemia in late gestation fetal sheep.

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.

Adrenocorticotropic Hormone↗
PubMed2000

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep.

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial PO(2) (PaO(2)) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 microg. kg(-1). min(-1)) or the alpha(1)-adrenergic agonist phenylephrine (6.5 microg. kg(-1). min(-1)) into the umbilical vein or during hypoxemia (fetal Pa(O(2)) reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an alpha(1)-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.

Adrenergic alpha-Agonists↗
PubMed2000

Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes.

Human epidemiological and animal experimental studies suggest that maternal undernutrition during pregnancy may alter cardiovascular development of the offspring. The extent to which these effects involve changes in fetal cardiovascular function and whether they are necessarily linked to reduced fetal growth is unknown. In sheep, we investigated the effect of a 15% reduction in maternal global nutrition for the first 70 days of gestation (term = 147 days) on fetal blood pressure development, baroreflex control of fetal heart rate (FHR), and cardiovascular responses to acute hypoxemia in late gestation. Basal mean arterial pressure (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and rate-pressure product (P < 0.001) were significantly lower in fetuses of nutritionally restricted ewes (R) compared with controls (C). FHR was not altered. The operating point for the fetal baroreflex was significantly lower in R fetuses compared with C (P < 0.01), but there was no difference between the groups in the cardiovascular response to hypoxemia. We conclude that mild maternal undernutrition alters fetal cardiovascular development, producing low blood pressure and resetting of baroreflex control mechanisms. This effect occurs without any changes in fetal growth or blood gas status.

Animals↗
PubMed2000

Hemodynamic and metabolic responses to moderate asphyxia in brain and skeletal muscle of late-gestation fetal sheep.

The purpose of this study was to investigate metabolic and hemodynamic responses in two fetal tissues, hindlimb muscle and brain, to an episode of acute moderate asphyxia. Near-infrared spectroscopy was used to measure changes in total hemoglobin concentration ([tHb]) and the redox state of cytochrome oxidase (COX) simultaneously in the brain and hindlimb of near-term unanesthetized fetal sheep in utero. Oxygen delivery (DO(2)) to, and consumption (VO(2)) by, each tissue was derived from the arteriovenous difference in oxygen content and blood flow, measured by implanted flow probes. One hour of moderate asphyxia (n = 11), caused by occlusion of the maternal common internal iliac artery, led to a significant fall in DO(2) to both tissues and to a significant drop in VO(2) by the head. This was associated with an initial fall in redox state COX in the leg but an increase in the brain. [tHb], and therefore blood volume, fell in the leg and increased in the brain. These data suggest the presence of a fetal metabolic response to hypoxia, which, in the brain, occurs rapidly and could be neuroprotective.

Acid-Base Equilibrium↗
PubMed2000

Selecting pilots with crew resource management skills.

For years, pilot selection has focused primarily on the identification of individuals with superior flying skills and abilities. More recently, the aviation community has become increasingly aware that successful completion of a flight or mission requires not only flying skills but the ability to work well in a crew situation. This project involved development and validation of a crew resource management (CRM) skills test for Air Force transport pilots. A significant relation was found between the CRM skills test and behavior-based ratings of aircraft commander CRM performance, and the implications of these findings for CRM-based selection and training are discussed.

Adult↗
PubMed2000

Characteristics of substance-abusing persons with schizophrenia: the paradox of the dually diagnosed.

Previous studies have noted the paradox of the dually-diagnosed (serious mental illness and substance abuse) in which the dually-diagnosed are judged to be both behaviorally more disorganized and simultaneously more socially competent. This study sought to further assess this paradox with a large sample size and a comprehensive assessment approach. In this study, the dually-diagnosed (N = 233) differed significantly from the non-dually-diagnosed (N = 262) in the symptom paradox. The dually-diagnosed were judged both more behaviorally disorganized and socially intact. The comprehensive assessment approach yielded empirical data in support of three possible hypotheses to explain the paradox. The implications of the findings and the three possible hypotheses are discussed.

Activities of Daily Living↗
PubMed1999

Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus.

1. The effects of fetal intravenous treatment with phentolamine or a vasopressinergic V1-receptor antagonist on the fetal cardiovascular responses to acute hypoxaemia in the llama were investigated. 2. Six llama fetuses were surgically prepared between 60 and 70 % of gestation under general halothane anaesthesia with vascular catheters and transit-time ultrasonic flow probes around a carotid artery and a femoral artery. At least 4 days after surgery all fetuses were subjected to a 3 h experiment: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery while on slow i.v. infusion with saline. On separate days this experiment was repeated with fetal i.v. treatment with either phentolamine or a V1-receptor antagonist dissolved in saline. 3. During saline infusion all llama fetuses responded to acute hypoxaemia with intense femoral vasoconstriction. Phentolamine during normoxia produced hypotension, tachycardia and vasodilatation in both the carotid and the femoral circulations. During hypoxaemia, fetuses treated with phentolamine did not elicit the pronounced femoral vasoconstriction and all died within 20 min of the onset of hypoxaemia. A V1-receptor antagonist produced a femoral vasodilatation during normoxia but did not affect the fetal cardiovascular responses to acute hypoxaemia. 4. In conclusion, alpha-adrenergic and V1-vasopressinergic mechanisms contribute to a basal vasoconstrictor tone in the femoral circulation in the llama fetus. The enhanced femoral vasoconstriction during acute hypoxaemia in the llama fetus is not mediated by stimulation of V1-vasopressin receptors, but is dependent on alpha-adrenergic receptor stimulation. Such alpha-adrenergic efferent mechanisms are indispensable to fetal survival during hypoxaemia in the llama since their abolition leads to cardiovascular collapse and death.

Adrenergic alpha-Antagonists↗
PubMed1999

Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development.

Experimental investigations in animals have highlighted the role of early reduced calorie and protein nutrition on fetal cardiovascular development, and the occurrence of a transition from a low fetal arterial blood pressure in late gestation to a high arterial blood pressure postnatally. These observations may explain the correlation between health, including appropriate nutrition, in pregnant women and the outcome of their pregnancies. Emphasis has been placed on low birth weight infants who have an increased risk of developing cardiovascular diseases, including hypertension, coronary heart disease and stroke in adulthood. Vascular pathology in adults is not always associated with low birth weight and animal experiments indicate that substantial changes in cardiovascular and endocrine function can result from maternal or fetal undernutrition without impairing fetal growth. Experimental investigation on organogenesis shows the pivotal role of adequate protein availability as well as total caloric intake. Amino acid metabolism in the feto-maternal unit appears to have a key influence on the development of organs involved in chronic degenerative disease in the adult. Experimental investigation has also highlighted the role of carbohydrate metabolism and its effect on the fetus in this respect. Either restriction of protein intake or diabetes in pregnant rats has intergenerational effects at least on the endocrine pancreas and the brain. Further investigation is needed to clarify the mechanisms involved and lead to a new understanding of the importance of nutrition during pregnancy. This will provide an important approach to the primary prevention of diabetes and chronic degenerative diseases.

Animal Nutritional Physiological Phenomena↗