Biomedical subjects
Publications and source records attributed to C J Edge.
Six to nineteen days after insertion of free flaps in oral defects three patients had secondary haemorrhages that necessitated the abolition of venous drainage in two cases and venous and arterial connections in the third. The flaps survived.
A case of a 64-year-old man with metastatic malignant mesothelioma is described in detail. When he presented to us he gave a history suggestive of transient ischaemic attack (TIA) 2 weeks before and 3 days after admission he developed weakness of the left upper limb. Computed tomographic scan of the brain revealed a solitary metastasis in the right cerebrum. A few days later, he developed subcutaneous metastasis in the chin. Malignant mesothelioma is considered to metastasize rarely and to spread locally. We suggest that distant metastasis in malignant mesothelioma is not uncommon and may be considered to behave like other forms of lung cancer. Treatment modalities should be studied in such patients.
The successful administration of a combined general and epidural anaesthetic to a patient with Brugada syndrome is reported. A review of the literature is presented.
A case of posterior spinal ligament rupture associated with a general anaesthetic for a laparoscopic cholecystectomy is reported. The role of the general anaesthetic in this case is discussed and a review of the literature is presented.
The conformational properties of oligosaccharides are important in determining their biological properties, such as recognition by proteins. The structural and dynamic properties of many oligosaccharides are poorly understood both because of a lack of experimental data (usually obtained from solution NMR parameters) and because of gross approximations frequently invoked in theoretical models. To characterise the oligomannose oligosaccharide Man,GlcNAc2 we have acquired a more extensive NMR data set and performed the first unrestrained molecular dynamics (MD) simulation in water of this large oligosaccharide (employing the GLYCAM_93 parameter set with the AMBER force field). Good agreement is seen between the computed dynamics data and the results of both an isolated spin pair (ISPA) analysis of short mixing time NOE data and NOE build-up curves for mixing times from 100 to 2000 ms. The number of experimental conformational constraints obtained in this study are in principle sufficient to fully define a rigid structure. The fact that this could not be done indicates a high degree of internal flexibility and/or the presence of multiple conformations about the glycosidic linkages. Independently, the same conclusions are reached from an analysis of the MD results. In addition, the theoretical results allow the overall topology of the molecule and its intra-molecular and solvent-mediated hydrogen bonding pattern to be defined. Extensive re-organisation of solvent and inter-residue hydrogen bonds is shown to be required for significant conformational changes to occur, resulting in relatively long life-times for distinct glycosidic linkage conformations, despite the high local flexibility of the glycosidic linkages. This factor is also seen in the overall topology of the molecule, where the considerable internal flexibility is not translated into gross changes in structure. The control exerted by the solvent over both the flexibility and overall topology of an oligosaccharide has important implications for recognition processes and for the conformational properties of glycans attached to glycoproteins.
A preliminary study to examine the hypothesis that the ability of well-controlled (defined as no hypoglycemic episodes within the last 12 mo., HbAlc < 9.0%, and none of the long-term complications of diabetes type I) diabetic scuba divers to control their serum glucose and dive without becoming hypoglycemic during a simulated dive to 27 meters of seawater in controlled environment is impaired. An open, controlled, crossover study compared blood glucose levels, hematocrits, and hematologic cell counts in a group of eight type I diabetic scuba divers to those from eight age- and sex-matched, normoglycemic control scuba divers. Each diver did one simulated dive and one control exercise on the surface on 2 consecutive days. The simulated dive was done to depth of 375 kPa in a hyperbaric chamber, the control exercise was done at ambient pressure. The order of the dive and the control exercise was randomized. No statistically significant differences were observed between serum glucose levels in the diabetic divers measured during the simulated dive to 375 kPa vs. the serum glucose levels in the diabetic divers measured during the control exercise at the same time points. All divers with type I diabetes remained free of symptoms and signs of hypoglycemia throughout the course of the trial, and no diabetic subject had a serum glucose less than 4 mmol/liter before the end of the trial. As the sample size was small, larger studies including subject with type II diabetes will be necessary to extend these results to the diabetic diving population at large. The authors conclude that, contrary to advice issued by most diving agencies to scuba divers, it may be safe to allow well-controlled subjects with type I diabetes with no long-term complications to undertake scuba diving, and that high partial pressures of oxygen do not seem to lower serum glucose levels significantly in the diabetic diver during the dive.
Exo- and endoglycosidases are used to sequence oligosaccharides and give valuable information on the monosaccharide sequence, together with the anomericity, the stereochemistry, and in some cases, the substitution pattern of the monosaccharides. Both sequential and parallel methods of oligosaccharide sequencing are discussed.
The effect of pressure was investigated on the readings of whole blood glucose obtained from the Bayer Glucometer 4 blood glucose meter which uses the hexokinase enzymatic reaction. Sixteen subjects (eight normal and eight insulin-dependent diabetics) were exercised in a hyperbaric chamber at a depth of 3.7 atm abs. Venous blood samples were monitored at regular intervals for whole blood glucose concentration as measured by a Glucometer 4 inside the chamber. The blood samples were immediately placed in an airlock and taken to 1 atm abs, where whole blood glucose concentrations were measured using an identical instrument. The remaining blood was then analyzed in duplicate for serum glucose concentration using standard laboratory methods. The results show a significant difference between whole blood glucose concentrations measured at pressure and those measured at atmospheric pressure. Significant differences are also observed between whole blood glucose concentrations measured under pressure and serum blood glucose concentrations measured at atmospheric pressure.
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A comparative analysis of carbohydrate libraries derived from cell lines binding E-selectin was used to identify endogenous protein-associated carbohydrate ligands for E-selectin. Three structures, which together constitute less than 1% of the total cell surface protein-associated carbohydrate, were unique to cell lines capable of binding E-selectin, including neutrophils and the monocytic cell line U937. All are tetra-antennary N-linked structures, with a sialic acid alpha 2 --> 3 galactose beta 1 --> 4 (fucose alpha 1 --> 3) N-acetyl glucosamine beta 1 --> 3 galactose beta 1 --> 4 (fucose alpha 1 --> 3) N-acetyl glucosamine lactosaminoglycan extension (sialyl-di-Lewis X [S-diLe(x)]) on the arm linked through the C4 residue on the mannose. While all contained the expected 3-SLe(x) sub-structure, these native structures have an additional fucosylated lactosamine unit. Direct evidence that these S-di-Lex-containing structures are high-affinity ligands for E-selectin came from the use of recombinant soluble E-selectin-agarose affinity chromatography. These three carbohydrate structures bound specifically to the E-selectin column, while 3-SLe(x) itself does not bind under identical conditions.
During pregnancy there is a dramatic reduction in the serum levels of agalactosyl IgG (G0IgG) in both normal women and those with rheumatoid arthritis. In order to determine if a similar reduction in G0IgG were apparent in fetal serum, a comparison of the galactose content of IgG from nine paired samples of umbilical vein or fetal blood and peripheral maternal serum, at gestational ages ranging from 16-41 weeks was performed. The full-term maternal IgG samples were highly galactosylated, so confirming previous observations of reduced G0IgG levels during pregnancy. In addition every paired sample of fetal IgG had a higher level of galactosylation than the corresponding maternal IgG. Therefore, during pregnancy there is both a reduced biosynthesis of the G0IgG glycoform by the mother, and a restriction of its transport across the placenta. The ratio of estimated G0IgG in fetal and maternal serum was found to be related to changes in IgG transport, and in particular the active transport of IgG1 across the placenta during gestation. Our data suggest that the placental IgG transport mechanism is either carbohydrate independent by discriminating for IgG1, or is carbohydrate dependent selecting for highly galactosylated IgG glycoforms. This study emphasizes the need for further investigations on the biological function of G0IgG in normal physiological states, in addition to disease states, such as juvenile and adult rheumatoid arthritis, where elevated G0IgG levels correlate with disease activity.
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Inflammation can be a beneficial response in the host for the control of infection and injury. However, occasionally, the inflammatory response can result in acute systemic collapse or, more frequently, a chronic reaction such as that observed in autoimmune disease, Crohn's disease and asthma. Injury to tissues or organs results in leukocyte adhesion to the endothelial cell surface, followed by diapedesis. Investigation of the initial leukocyte-endothelium adhesion processes has clearly shown the involvement of an inducible set of molecules, called selectins, on the endothelial and leukocyte cell surfaces. These molecules are of interest as the interactions with their respective ligands appear to involve carbohydrates. The exact nature of these interactions is still being elucidated. Therapeutic intervention using carbohydrate small-molecule mimetics may be beneficial in the modification of the inflammatory process.
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The site-specific glycosylation of soluble recombinant variants of human and rat CD4 (sCD4) expressed in Chinese hamster ovary (CHO) cells has been characterized. The presence of identical oligosaccharides at the conserved glycosylation site in domain 3 of rat and human sCD4 and the greater abundance of oligomannose and hybrid type glycans at the non-conserved glycosylation site of rat sCD4 clearly indicate that the protein structure influences oligosaccharide processing. Comparisons of rat sCD4 glycopeptides with mutant molecules with only single glycosylation sites and with a truncated form containing only the two NH2-terminal domains, indicate that independent processing occurs at each glycosylation site and that domain interactions can also affect oligosaccharide processing. These and other analyses of sCD2 expressed in CHO cells and Thy-1 purified from various tissues suggest that the diversity of oligosaccharide structures on a protein is regulated by the location of the glycosylation sites and the nature of the target protein, cell and tissue. The functional significance of this control remains to be determined.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.