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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 55 records · Page 3Linked to original sources
PubMed1999

L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery.

BACKGROUND: The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery. METHODS AND RESULTS: Ten patients (aged 0.62+/-0.27 years) with pulmonary hypertension undergoing cardiac catheterization who had not had surgery and 10 patients (aged 0.65+/-0.73 years) who had recently undergone cardiopulmonary bypass were examined. All were sedated and paralyzed and received positive-pressure ventilation. Blood samples and pressure measurements were taken from catheters in the pulmonary artery and the pulmonary vein or left atrium. Respiratory mass spectrometry was used to measure oxygen uptake, and cardiac output was determined by the direct Fick method. PVR was calculated during steady state at ventilation with room air, during FIO(2) of 0.65, then during additional intravenous infusion of L-Arg (15 mg. kg(-1). min(-1)) and Sub-P (1 pmol. kg(-1). min(-1)), and finally during inhalation of NO (20 ppm). In preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting PED. Postoperative PVR was higher, with an additional pulmonary endothelial contribution that was restorable with L-Arg and Sub-P. CONCLUSIONS: Postoperatively, the rise in PVR suggested PED, which was restorable by L-Arg and Sub-P, with no additional effect of inhaled NO. These results may indicate important new treatment strategies for these patients.

Administration, Inhalation↗
PubMed1999

Phospholipase D and membrane traffic. Potential roles in regulated exocytosis, membrane delivery and vesicle budding.

It is now well-established that phospholipase D is transiently stimulated upon activation by G-protein-coupled and receptor tyrosine kinase cell surface receptors in mammalian cells. Over the last 5 years, a tremendous effort has gone to identify the major intracellular regulators of mammalian phospholipase D and to the cloning of two mammalian phospholipase D enzymes (phospholipase D1 and D2). In this chapter, we review the physiological function of mammalian phospholipase D1 that is synergistically stimulated by ADP ribosylation factor, Rho and protein kinase Calpha. We discuss the function of this enzyme in membrane traffic, emphasising the possible integrated relationships between consumption of vesicles in regulated exocytosis, membrane delivery and constitutive membrane traffic.

ADP-Ribosylation Factors↗
PubMed1999

Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.

BACKGROUND: Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia. METHODS: In this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rhône-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times. RESULTS: Dialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed. CONCLUSIONS: This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.

Adult↗
PubMed1999

Self-regulating interest: the moderating role of hardiness and conscientiousness.

Sansone, Weir, Harpster, and Morgan (1992) found that individuals intentionally regulated their interest in an activity when they had both the need (the task was boring) and a reason to exert the effort (an ostensible health benefit). The present study examined Hardiness and Conscientiousness as moderators of this self-regulatory process when individuals had the option of quitting in addition to the options of persisting and of engaging in interest-enhancing strategies. Undergraduates performed a boring copying activity under instructions to stop when they felt they could evaluate the task. Half were told that their evaluations would help researchers develop good jobs for others (Benefit). Results indicated high hardy individuals copied more letters when they were provided the additional Benefit information, and this effect was mediated through their attempt to make the task more interesting. High conscientious individuals persisted longer than individuals lower in conscientiousness independently of the benefit manipulation or strategy use. Implications of individual differences in self-regulation of motivation are discussed.

Achievement↗
PubMed1999

Continuous neonatal blood gas monitoring using a multiparameter intra-arterial sensor.

AIMS: To compare arterial blood gas (ABG) readings obtained with a multiparameter intra-arterial sensor with those from an ABG analyser. METHODS: An MPIAS with the ability to measure continuously pH, PaCO2, and PaO2 was introduced via an umbilical arterial catheter in 27 neonates requiring intensive care. They underwent 3260 hours of MPIAS monitoring, during which 753 ABG readings were performed. RESULTS: Overall bias (mean difference: MPIAS-ABG) and precision (standard deviation of differences) values were: -0.002 and 0.022, respectively, for pH; +0.26 and 0.52 for PaCO2 (kPa); and -0.19 and 0.99 for PaO2 (kPa). This gave 95% limits of agreement as: -0.047 to +0.042 for pH, -0.76 to +1.28 kPa for PaCO2, and -2.13 to +1.75 kDa for PaO2. For each variable, precision across readings from the same individual was better than overall precision for all data. No complications related to the use of the catheter were observed. CONCLUSIONS: Continuous MPIAS ABG monitoring is an exciting development, with the potential to reduce blood transfusions and improve ABG homeostasis.

Blood Gas Analysis↗
PubMed1999

Growth of human tumor cells in macroporous microcarriers results in p53-independent, decreased cisplatin sensitivity relative to monolayers.

Multicellular contact has been shown to influence the in vitro sensitivity of cells to drug treatment. We investigated the use of macroporous gelatin microcarriers, CultiSpher-G, as a convenient laboratory system for the molecular analysis of this "contact effect". We determined that human A549 cells can be grown in CultiSphers with growth and cell cycle parameters similar to those of monolayers. In addition, cells in CultiSphers express less p27/kip1, an indicator of cell cycle arrest, than equivalent cells in monolayers. When treated with drugs, A549 cells grown in CultiSphers or monolayers accumulate equivalent amounts of platinum-DNA adducts and similar amounts of doxorubicin. Moreover, A549 and KB-3-1 cells in CultiSphers have significantly decreased sensitivity to cis-platinum(II)diammine dichloride (cisplatin), 4-hydroperoxycyclophosphamide, doxorubicin, and paclitaxel (taxol) compared with cells in monolayers when assayed by clonogenic survival. Cisplatin treatment in monolayers or CultiSphers did not result in apoptotic cell death. In contrast, paclitaxel caused a significant amount of sub-G1 DNA, an indicator of apoptosis, which was diminished when cells were grown in CultiSphers compared with monolayers. When grown in CultiSphers, cells with abrogated p53 function (A549/16E6 and NCI-H1299) were less sensitive to cisplatin than the corresponding monolayer cells, indicating that the decrease in sensitivity is p53 independent. Taken together, the data suggest that CultiSpher-G microcarriers are a useful in vitro system to examine the effects of three-dimensional cell contact on drug sensitivity of human tumor cells.

Antineoplastic Agents↗
PubMed1998

A novel method of purifying lung surfactant proteins A and D from the lung lavage of alveolar proteinosis patients and from pooled amniotic fluid.

A simple procedure has been developed for the purification of the surfactant proteins SP-A and SP-D from lung lavage of patients with alveolar proteinosis. The SP-D is purified by fractionation of the supernatant obtained after spinning the lavage at 10000 X g for 40 min, while the bulk of the SP-A is purified by fractionation of the pellet. The supernatant is applied to a maltosyl-agarose column and the bound SP-D is specifically eluted using MnCl2. The pellet is solubilised in 6 M urea and, following renaturation, the solubilised proteins are applied to maltosyl-agarose and SP-A eluted using a gradient of EDTA. Both SP-A and SP-D are further purified by gel-filtration on Superose-6. This procedure has also been used to prepare successfully human SP-A and SP-D from amniotic fluid and may be generally applicable to the isolation of these surfactant proteins from lung washings obtained from other species.

Amniotic Fluid↗
PubMed1998

ADP-ribosylation factor and Rho proteins mediate fMLP-dependent activation of phospholipase D in human neutrophils.

Activation of intact human neutrophils by fMLP stimulates phospholipase D (PLD) by an unknown signaling pathway. The small GTPase, ADP-ribosylation factor (ARF), and Rho proteins regulate the activity of PLD1 directly. Cell permeabilization with streptolysin O leads to loss of cytosolic proteins including ARF but not Rho proteins from the human neutrophils. PLD activation by fMLP is refractory in these cytosol-depleted cells. Readdition of myr-ARF1 but not non-myr-ARF1 restores fMLP-stimulated PLD activity. C3 toxin, which inactivates Rho proteins, reduces the ARF-reconstituted PLD activity, illustrating that although Rho alone does not stimulate PLD activity, it synergizes with ARF. To identify the signaling pathway to ARF and Rho activation by fMLP, we used pertussis toxin and wortmannin to examine the requirement for heterotrimeric G proteins of the Gi family and for phosphoinositide 3-kinase, respectively. PLD activity in both intact cells and the ARF-restored response in cytosol-depleted cells is inhibited by pertussis toxin, indicating a requirement for Gi2/Gi3 protein. In contrast, wortmannin inhibited only fMLP-stimulated PLD activity in intact neutrophils, but it has no effect on myr-ARF1-reconstituted activity. fMLP-stimulated translocation of ARF and Rho proteins to membranes is not inhibited by wortmannin. It is concluded that activation of Gi proteins is obligatory for ARF/Rho activation by fMLP, but activation of phosphoinositide 3-kinase is not required.

ADP-Ribosylation Factor 1↗
PubMed1998

Pyruvate augments mechanical function via activation of the pyruvate dehydrogenase complex in reperfused ischemic immature rabbit hearts.

BACKGROUND: Reperfusion of ischemic adult hearts is associated with increased fatty acid oxidation, reduced pyruvate oxidation, and reduced pyruvate dehydrogenase (PDH) activity, leading to a decrease in cardiac efficiency. These effects may be amplified in newborn hearts because of the immaturity of their PDH pathway. We hypothesize that pyruvate can augment mechanical function in the immature heart by activating the PDH complex (PDC) during reperfusion in severely ischemic hearts. MATERIALS AND METHODS: Seven-day old isolated working rabbit hearts (n = 12) were perfused with modified Krebs solution containing 0.4 mM palmitate. Pyruvate (5 mM) was added for a 10-min period either before or after a 30-min period of normothermic global ischemia. Cardiac functional indices before global ischemia and during reperfusion were correlated with active and total PDC activity measured in 28 additional hearts frozen at the various time points throughout the perfusion protocol. RESULTS: Addition of pyruvate before ischemia increased the proportion of active PDC but did not affect any measured functional indices. During early reperfusion, aortic flow, cardiac output, and cardiac work were all significantly depressed compared to preischemic values. Addition of pyruvate significantly increased the proportion of active PDC and was also associated with a significant increase in aortic flow, cardiac work, and developed pressure. Removal of pyruvate from the perfusate resulted in a subsequent significant decrease in PDC activity and these functional parameters. CONCLUSION: During reperfusion of neonatal rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC.

Animals↗
PubMed1998

Is bed rest following embryo transfer necessary?

OBJECTIVE: To evaluate the effect of no bed rest following ET on the results of an IVF program. DESIGN: Historical cohort-control study. SETTING: A University-based assisted conception unit. PATIENT(S): One thousand and nineteen (1019) IVF cycles were performed at our unit from June 1994 to August 1996. The historical control consisted of all the 19,697 IVF cycles reported in the United Kingdom national database from April 1994 to March 1995. INTERVENTION: No bed rest following ET in our patients. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) and clinical PR per cycles started and per ET procedure. RESULT(S): The clinical PR per ET was significantly higher in our patients than in the national data (30% versus 22.9%), as was the clinical PR per cycle (23.5% versus 18.6%). The implantation rate in our patients was 17.2%. CONCLUSION(S): The favorable PR in our patients despite no bed rest following ET suggests the bed rest is not necessary.

Bed Rest↗
PubMed1998

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II.

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n=10) and standard Prematil (n=10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n=11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34g kg(-1) (82.0), 2.64g kg(-1) (82.9) and 1.65g kg(-1) (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n-6 LCP (p < 0.01). Nevertheless, excreted LCP equated to < 30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.

Analysis of Variance↗
PubMed1998

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids.

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP (n = 20) and standard Aptamil (n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group (n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg[-1]) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil (p < 0.01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.

Analysis of Variance↗
PubMed1998

Nurses performing embryo transfer: the development and results of the Birmingham experience.

Although in-vitro fertilization treatment is doctor-led, many of its steps are performed by nurses. The embryo transfer step, however, is performed exclusively by doctors in the majority of units. In our unit, doctors performed embryo transfers from June 1994 until December 1995 (period I). From January 1996 until May 1997 (period II) the nurses, after appropriate training, performed the procedure. When they experienced difficulties during the mock transfer performed immediately before the real transfer, or if they were not available to do the procedure, a doctor performed it. In period I, 488 embryo transfers were performed (all by doctors), with a pregnancy rate per transfer of 35% and an implantation rate of 16%. In period II, 522 embryo transfers were performed. Nurses performed 371 (71%) and doctors 151 (29%) of the procedures. The pregnancy rate per nurse-transfer was 40.2% and per doctor-transfer 41%. The corresponding implantation rates were 16.9% and 17%. None of these differences were statistically significant (P > 0.05). These data indicate that, with appropriate training and medical back-up, nurses can perform the majority of embryo transfers with ease and outcome comparable to that of doctor embryo transfer.

Embryo Implantation↗
PubMed1998

Laminin blocks the assembly of wild-type A beta and the Dutch variant peptide into Alzheimer's fibrils.

Amyloid fibril formation is believed to be a nucleation-dependent polymerization process which may be influenced by various other factors with important consequences for the development, prevention or treatment of amyloidosis. We have previously shown that laminin inhibits A beta peptide fibril formation in vitro. Here we present a kinetic study that indicates laminin to be a potent anti-amyloidosis factor, as it not only inhibited A beta 1-40 fibril aggregation, but also inhibited the aggregation of the Dutch A beta 1-40 variant, a peptide with a higher capacity to aggregate than the wild-type A beta 1-40. The inhibitory effect of laminin on amyloid fibril formation was not overcome by the addition of pre-formed A beta fibrils, suggesting that laminin inhibits the fibril elongation process. At the present time, however, we cannot rule out the possibility that laminin also affects the initial nucleation process of A beta fibril formation. On other hand, laminin was not able to counteract the amyloid fibril formation promoted by acetylcholinesterase (AChE), another component of the amyloid deposits found in AD brains. The effect of laminin may be important as an inhibitor of A beta amyloidogenesis in vivo, specifically at the level of cerebral blood vessels.

Acetylcholinesterase↗
PubMed1997

Managing admissions. Bed spreads.

A decrease in surgical beds left a trust insufficient flexibility to increase an already high throughput without affecting the quality of care. Changes in the management of surgical admissions, including the appointment of an admissions co-ordinator, have improved co-ordination of elective and emergency admissions. Three years later maximum waiting times had fallen from 18 to 10 months. In the first nine months of the new booking system, the number of operations cancelled on the day because of bed nonavailability fell by half, while patients cancelled on the day of admission dropped by 36 per cent.

Admitting Department, Hospital↗
PubMed1997

Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule.

We have purified a previously unknown glycoprotein (designated gp-340) from human bronchioalveolar lung washings from a patient with alveolar proteinosis. gp-340 was identified by its calcium-dependent binding to lung surfactant protein D (SP-D) and by its molecular mass of 340 kDa in the reduced state on SDS-polyacrylamide gel electrophoresis (PAGE). gp-340 was purified from the 10,000 x g pellet of the lavage fluid by ion-exchange and gel permeation chromatography. On SDS-PAGE, gp-340 showed an apparent molecular mass of 290 kDa in the unreduced state. On gel chromatography under non-dissociating conditions, the apparent molecular mass of gp-340 was >1000 kDa. The presence of N-linked glycosylation was shown by digestion with N-glycosidase F, which reduced the apparent molecular mass of gp-340 under reducing condition to about 300 kDa. Partial amino acid sequence data showed the presence of scavenger-receptor type domains. Monoclonal and polyclonal antibodies were raised against gp-340, and their specificities were confirmed by Western blotting. The antibodies were used for immunohistochemical localization of gp-340 in the lung, where it was found on the surface of and within alveolar macrophages. Direct binding between gp-340 and SP-D took place at physiological ionic strength, required the presence of calcium, and was not inhibited by maltose. The binding between SP-D and mannan also required the presence of calcium, but this interaction was completely inhibited by maltose. The same binding pattern was seen between gp-340 and recombinant human SP-D composed of the trimeric neck region and three carbohydrate recognition domains. These findings indicate that the binding between gp-340 and SP-D is a protein-protein interaction rather than a lectin-carbohydrate interaction and that the binding to gp-340 takes place via the carbohydrate recognition domain of SP-D. We conclude that gp-340 is a new member of the scavenger-receptor superfamily and likely to be a truncated form of a receptor for SP-D.

Amino Acid Sequence↗
PubMed1997

Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: comparison to class I proteins.

The structure and thermal stability of empty and peptide-filled forms of the murine class II major histocompatibility complex (MHC) molecule I-E(k) were studied at neutral and mildly acidic pH. The two forms have distinct circular dichroic spectra, suggesting that a conformational change may accompany peptide binding. Thermal stability profiles indicate that binding of peptide significantly increases the thermal stability of the empty heterodimers at both neutral and mildly acidic pH. Free energies calculated from these data provide a direct measure of this stabilization and show that the empty form of I-E(k) is significantly more stable than that of class I MHC proteins. Furthermore, for the two MHC class II proteins that were analyzed (I-E(k) and I-A(d)), thermal stability was not significantly altered by acidification. In contrast, of four class I MHC molecules studied, three have shown a significant loss in complex stability at low pH. The marked stability exhibited by their empty form, as well as their resistance to low pH, as observed in this study, correlate well with the ability of class II MHC molecules to traverse and bind peptides in acidic endosomal vesicles.

Amino Acid Sequence↗