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Biomedical subjects

E Lowe

Publications and source records attributed to E Lowe.

At least 19 recordsLinked to original sources
PubMed2003

The influence of His94 and Pro149 in modulating the activity of V. cholerae DsbA.

DsbA is the primary catalyst of disulfide bond formation in the periplasm of gram-negative bacteria. Numerous theoretical and experimental studies have been undertaken to determine the molecular mechanisms by which DsbA acts as a potent oxidant, whereas the homologous cytoplasmic protein, thioredoxin, acts as a reductant. Many of these studies have focused on the nature of the two residues that lie between the active-site cysteines. Although these are clearly important, they are not solely responsible for the differences in activity between these thiol-disulfide oxidoreductases. Q97 in the helical domain of E. coli DsbA has been implicated in influencing the redox potential of E. coli DsbA. In V. cholerae DsbA, the analogous residue is H94. In this study, the effect of H94 on the oxidase activity of DsbA is examined, along with the role of the conserved cis-proline residue P149. The DsbA mutant H94L shows a nearly fourfold increase in activity over the wild-type enzyme. To our knowledge, this is the first time an increase in the normal activity of a thiol-disulfide oxidoreductase has been reported. Potential reasons for this increase in activity are discussed.

Histidine↗
PubMed2001

A (1-->3)-beta-D-linked heptasaccharide is the unit ligand for glucan pattern recognition receptors on human monocytes.

Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a K(d) of 31 microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFkappaB-dependent signaling pathways or protection against experimental sepsis.

Animals↗
PubMed2001

Identification of factors contributing to increased length of stay in two diagnosis related groups.

This paper discusses a study conducted to identify factors that contributed to increased length of stay for two diagnosis related groups (DRGs) and their consequential impact on nursing salaries. The study shows that three separate clusters of cost drivers (DRG-related, nurse-related, and patient-related) contributed to increased length of stay for DRG 177 (chronic obstructive airways disease) and DRG 367 (cholecystectomy without exploration of the common bile duct). It was not possible to establish a link between length of stay and nursing salaries due to lack of relevant data. The results of the study can be used to raise professional awareness to the difficulties encountered by nurse managers in controlling length of stay when there are substantial numbers of different DRGs in acute care wards. The results can also be used as a basis for conducting larger studies into DRGs with higher than expected lengths of stay.

Cholecystectomy↗
PubMed1999

Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine.

Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase.

Aldehyde Oxidase↗
PubMed1995

The limits of the possible: models of power supply and demand in cycling.

This paper outlines a general strategy for mathematical modeling of cycling performance. This strategy involves formulating one expression describing the power available for external work from physiological sources. The variables used in this expression include maximal aerobic power (VO2max), fractional utilisation of VO2max, mechanical efficiency, maximal accumulated oxygen deficit, and the time constants relating to the expression of aerobic and anaerobic capacities. A second expression describing the power demand of cycling is then constructed. The variables used in this expression include the mass, projected frontal area and drag characteristics of the system, the coefficient of rolling resistance, environmental variables such as temperature, barometric pressure, relative humidity, wind speed and direction and the slope of the course. The two expressions are equated and solved using an iterative procedure. Two series of trials were used to assess the predictive accuracy of the model, one using track endurance performances and the other a 26 km road time-trial. The correlations between actual and predicted times have been excellent (0.92-0.95, p < or = 0.0001), with small mean differences (0-1.83% of mean performance time) and mean absolute differences (1.07-3.24%). The model allows us to make predictions about the effect of equipment changes and environmental factors, to compare performances under very different conditions, and to predict the limits of the possible in cycling performance. A range of options designed to improve cycling performance is described.

Bicycling↗
PubMed1989

Efficacy of intraoperative transesophageal echocardiography in children with congenital heart disease.

The feasibility and potential adverse effects of using intraoperative transesophageal echocardiography (TEE) in 19 children ages 7.5 to 16 years undergoing surgical repair of a variety of congenital heart defects were evaluated. The ability of TEE to assess the adequacy of surgical repair as well as left ventricular function and wall motion abnormalities in this setting was also examined. Intraoperative transesophageal 2-dimensional and Doppler evaluation, and, in selected patients, echo-contrast and color flow imaging, were performed with either a 3.5- or 5.0-MHz phased array probe mounted within the tip of a flexible gastroscope. Probe insertion was successful in 18 of 19 patients. Fiberoptic endoscopy (9 patients) and autopsy (1 patient--cardiac donor) performed within 24 hours of surgery demonstrated no significant esophageal abnormalities. Intraoperative wall motion abnormalities were identified in 8 patients but did not persist after the operation. An adequate surgical repair was demonstrated by contrast and color flow imaging in most patients. Microcavitation was detected in 6 patients for greater than 5 minutes after a standard debubbling procedure. No patient displayed any adverse neurologic effects. It is concluded that, with the currently available probes, intraoperative TEE can be performed safely and reliably in children as young as 7.5 years of age. The procedure provides valuable information regarding wall motion abnormalities, cardiac function and the adequacy of surgical repair.

Adolescent↗
PubMed1989

Peritoneal washing cytology: a retrospective analysis of 175 gynaecological patients.

Accurate staging is the basis for optimal therapy in the management of the gynaecological cancer patient and, in recent years, peritoneal washings are one of the techniques used to determine this, both at the initial and subsequent laparotomies. Two hundred and four peritoneal washes were obtained from 175 patients during a 5-year period. Fifteen cases of histologically proven intraperitoneal tumour were confirmed in 11 cases by periotoneal cytology at initial operation, a sensitivity of 73%. At second-look laparotomy, 3 of 9 histologically proven malignancies were confirmed by cytology, a sensitivity of 33%. One false positive diagnosis was made in the series. Procedures to avoid both false-positive and false-negative diagnoses by the clinician and the laboratory are discussed, and a review of the literatue is provided.

Cytodiagnosis↗
PubMed1967

Protein synthesis by microsomal particles from regenerating rat liver.

1. Washed microsome particles from regenerating liver were shown to incorporate [(14)C]leucine into protein more actively than similar preparations from normal liver. 2. The total incorporation in the preparations from regenerating liver increased linearly with the amount of protein incubated, whereas this was not so with preparations from normal liver. 3. The greater activity of regenerating-liver microsomes appeared to be associated with the bound polysomes. 4. The size distribution of polysomes obtained after removal of membrane with deoxycholate was the same in normal and regenerating liver. 5. In general the activity of polysome preparations from normal and regenerating liver was similar. 6. It is concluded that the greater activity of the particles in the microsome fraction from regenerating liver is to be attributed to the ribosomes bound to membrane and that their activity is controlled by factors present in the membrane.

Animals↗
PubMed1965

Studies on the protein-synthesizing activity of the ribosomes of rat liver. The activity of free polysomes.

1. The activities of microsome fractions from the liver of adult and 5-day-old rats for the incorporation of [(14)C]phenylalanine into protein were similar in the presence and absence of polyuridylic acid. 2. The activity of a light-microsome fraction from adult liver was greater than that of a heavy-microsome fraction, and the light-microsome fraction was also more markedly stimulated by the presence of polyuridylic acid. 3. The light-microsome fraction, when analysed by density-gradient centrifugation, contained a higher ratio of free ribosomes to bound ribosomes, whereas the reverse was true for the heavy-microsome fraction. Similar results were obtained for liver from adult and 5-day-old rats. 4. When the light-microsome fraction was incubated under conditions in which amino acid was incorporated into protein there was only a small increase in the ratio of free to bound ribosomes. When such a fraction was incubated with [(14)C]leucine and was then subjected to density-gradient centrifugation the fraction with the highest specific activity based on RNA had a density between that of the bound and free ribosomes. Treatment of the incubated fraction with ribonuclease shifted the radioactivity towards the free ribosome peak. These properties are consistent with the presence of active free polysomes. Such a component appeared also to be present when the heavy-microsome fraction was incubated under similar conditions. 5. The effect of the presence of polyuridylic acid on the incorporation of [(14)C]phenylalanine by the light-microsome fractions from liver of adult and 5-day-old rats was greatest in the region of the free ribosomes, but it is probable that some small polysomes containing polyuridylic acid are formed. 6. Polyuridylic acid also stimulated the bound ribosomes to a small extent when the heavy-microsome fraction from the liver of young rats was incubated with [(14)C]phenylalanine. 7. The results are discussed in terms of the various morphological constituents in liver now known to play a role in the synthesis of protein for export and for the internal activity of the cell.

Animals↗