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Biomedical subjects

S Abbas

Publications and source records attributed to S Abbas.

14 recordsLinked to original sources

Structural requirements for the carbohydrate ligand of E-selectin.

The acute inflammatory response requires that circulating leukocytes adhere to, and then migrate through, the vascular wall at the site of injury or infection. Several receptors have been implicated in this adhesion and migration process, including the selectins, a family of carbohydrate-binding proteins. The ligand for one of these proteins, E-selectin (LECAM-2, ELAM-1) has been described by several groups to contain a polylactosamine structure bearing a terminal sialic acid residue and at least one fucose residue. We report here a more detailed investigation into the minimum structural requirements for carbohydrate recognition by E-selectin. Using both direct binding and inhibition studies we demonstrate that the sialyl Lewisx tetrasaccharides Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, and Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]Glc are the smallest oligosaccharides recognized by the lectin. In addition, an oligosaccharide containing the sialyl Lewisa epitope is also recognized, but less avidly. We propose a structural model of functional groups necessary for recognition by E-selectin, based on these data and additional experiments on modifications of sialic acid and the reducing terminal saccharide.

Animals

Non-reducing terminal linkage position determination in intact and permethylated synthetic oligosaccharides having a penultimate amino sugar: fast atom bombardment ionization, collisional-induced dissociation and tandem mass spectrometry.

Certain linkage positions in oligosaccharides can be discerned by collision-activated dissociation mass spectrometry, rationalized by molecular modelling. Previous work on synthetic oligosaccharides has suggested that daughter ion patterns can distinguish among intact compounds which terminate in alpha-L-fucose and have a penultimate amino sugar. The current study indicates that these observations can be extended to oligosaccharides terminating in beta-D-galactose. In addition, we have observed that protonated, ammoniated and lithiated molecular ions all produce linkage-specific daughter ion spectra in these two sets of oligosaccharides. Sodiated molecular ions could be fragmented usefully under high collision energy offset conditions; potassiated ions were stable and not dissociable under conditions available in a triple-quadrupole instrument. We also show linkage discernment among the permethylated set of these six synthetic oligosaccharides. Methylated derivatives of this set of compounds give more useful product ions, including a 3-linkage specific ion. A novel relationship was noted by a plot of collision energy against (daughter ion/parent ion) ratio, which gave a unique slope for each of the non-reducing terminal linkage positions 3, 4 and 6 in the set of six compounds. The slope of this plot is related to the ability of each linkage position in the oligosaccharide to absorb collisional energy. Rotational freedom of the individual glycosidic linkage is hypothesized to play a role in this phenomenon.

Amino Sugars

Comparative trial of erythromycin and sulphatrimethoprim in the treatment of tetracycline-resistant Vibrio cholerae O1.

The efficacy of the 2 antimicrobial compounds, erythromycin and trimethoprim-sulphamethoxazole, were compared in the treatment of the clinical symptoms of cholera and the eradication of Vibrio cholerae O1 organisms from the stools of patients infected with tetracycline-resistant strains. 47 patients with a clinical diagnosis of cholera, without prior antibiotic therapy, were included in the trial and received either erythromycin, trimethoprim-sulphamethoxazole, or a placebo twice daily. The mean number of vibrios per gram of stool decreased from 5.2 x 10(8) +/- 0.3 per ml to 0 within 36 h of admission following either erythromycin or trimethoprim-sulphamethoxazole therapy, while organisms persisted in placebo-treated controls for more than 7 d. Clinically there was a significant reduction in the number of diarrhoeal stools per day and duration of diarrhoea in the erythromycin-treated group compared with the placebo-treated controls. During the study an isolate resistant to trimethoprim-sulphamethoxazole but sensitive to erythromycin was obtained. As an adjunct to oral rehydration therapy, erythromycin may serve as an effective alternative treatment for cholera, especially in areas where trimethoprim-sulphamethoxazole resistance may be emerging.

Adolescent

DIABETEX decision module 2--calculation of insulin dose proposals and situation recognition by means of classifiers.

Current research in the field of medical decision making tries to represent and to analyse complex, uncertain and complicated situations. The first version of DIABETEX, which is a decision support system for the treatment of diabetic out-patients, accepts the challenge to overcome these difficulties. It includes a network of rules on the basis of known glucose-insulin relationships under different situations. The insulin dose for type I diabetic patients is suggested accordingly. In this, the application of special cybernetic methods offers the chance to overcome complexity, uncertainty, fuzzyness and incompleteness of data. Two methods of classification are presented to complete the DIABETEX decision unit: (1) the Bayes' classification is used in the calculation of insulin doses for type I diabetic patients on multiple subcutaneous insulin injections considering the basis-bolus concept; (2) fuzzy classification is employed in separating 'normal diabetic days' from days with information on special situations such as exercise, illness, menstruation on the one side, from stress, hypoglycaemia etc. on the other.

Bayes Theorem