Biosynthesis of the escherichia coli K4 capsule polysaccharide. A parallel system for studies of glycosyltransferases in chondroitin formation

Escherichia coli K4 bacteria synthesize a capsule polysaccharide (GalNAc-GlcA(fructose))n with the carbohydrate backbone identical to chondroitin. GlcA- and GalNAc-transferase activities from the bacterial membrane were assayed with acceptors derived from the capsule polysaccharide and radiolabeled UDP-[14C]GlcA and UDP-[3H]GalNAc, respectively. It was shown that defructosylated oligosaccharides (chondroitin) could serve as substrates for both the GlcA- and the GalNAc-transferases. The radiolabeled products were completely degraded with chondroitinase AC; the [14C]GlcA unit could be removed by beta-D-glucuronidase, and the [3H]GalNAc could be removed by beta-N-acetylhexosaminidase. A fructosylated oligosaccharide acceptor tested for GlcA-transferase activity was found to be inactive. These results indicate that the chain elongation reaction of the K4 polysaccharide proceeds in the same way as the polymerization of the chondroitin chain, by the addition of the monosaccharide units one by one to the nonreducing end of the polymer. This makes the biosynthesis of the K4 polysaccharide an interesting parallel system for studies of chondroitin sulfate biosynthesis. In the biosynthesis of capsule polysaccharides from E. coli, a similar mechanism has earlier been demonstrated for polysialic acid (NeuNAc)n (Rohr, T. E., and Troy, F. A. (1980) J. Biol. Chem. 255, 2332-2342) and for the K5 polysaccharide (GlcAbeta1-4GlcNAcalpha1-4)n (Lidholt, K., Fjelstad, M., Jann, K., and Lindahl, U. (1994) Carbohydr. Res. 255, 87-101). In contrast, chain elongation of hyaluronan (GlcAbeta1-3GlcNAcbeta1-4)n is claimed to occur at the reducing end (Prehm, P. (1983) Biochem. J. 211, 181-189).     

The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs

OBJECTIVE AND DESIGN: We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an anti-glucocorticoid in rat endotoxin-induced uveitis (EIU). In the present study, we produced EIU in guinea pigs and investigated the effects of betamethasone dipropionate on the EIU. MATERIAL: Male Hartley guinea pigs were used. TREATMENT: Glucocorticoids were instilled into the eye. METHOD: To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. Prostaglandin E2 (PGE2) production after LPS injection into the anterior chamber was also examined. RESULTS: Intracameral injection of LPS (1 microgram/eye) induced cell infiltration into the anterior chamber and PGE2 production. Betamethasone dipropionate inhibited cell infiltration and PGE2 production more strongly than betamethasone. These results suggest that betamethasone dipropionate is a potent glucocorticoid in guinea pigs. CONCLUSIONS: Structure-activity relationships of glucocorticoids in the guinea pig EIL model may differ from those in the rat EIU model.     

Identification of novel exons 3'' to the human SNRPN gene

This paper examines the relationship between self-efficacy and social power (expert and referent) and how the application of this relationship, leads to client adherence and compliance. Referent power is defined, including methods that health care professionals may use to develop and apply referent power. Expert power is defined and addressed in the context of referent power, self-esteem and self-efficacy as a means of promoting adherence. Self-efficacy as a concept is defined and explored in the context of social power. The relationships between self-efficacy and social power (expert and referent) are shown as important determinants of adherence and compliance. The theory of the application of referent and expert power in relationship with self-efficacy has been compared with an effective programme, yielding high compliance, at Western Psychiatric Institute and Clinic, showing the theory's relevance and applicability in determining compliance. Explored are the reasons for non-compliance in the elderly population and how the theory model can remedy these detriments for compliance. The empowerment of elderly patients through the application of this theory to medication compliance is examined. The determination of adherence and compliance is shown by the application of the relationship between self-efficacy and both expert and referent power.     

Laparoscopic operation of a Morgagni hernia

Morgagni hernias are the least common form of diaphragmatic hernias. Although they are congenital, most of them are not diagnosed until later in life. The indication for surgery is based on the patient's symptoms or on the radiological evidence of incarcerated tissue, and until quite recently involved a laparotomy or thoracotomy. Laparoscopy not only permits the suspected diagnosis to be confirmed--which is otherwise often difficult--but also makes it possible to close the hernia site by suturing. For improved security, the hernia site is augmented by fixing in place a non-absorbable mesh. The operative technique employed is described.     

A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia

The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.     

Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.     

Differences in the yields of dicentrics and reciprocal translocations observed in the chromosomes of irradiated human skin fibroblasts and blood lymphocytes from the same healthy individuals

The modulatory role of locally produced cyclooxygenase products and endothelium-derived nitric oxide in controlling vascular tone was investigated in bovine intra-mammary artery. Vascular reactivity initiated by vasoactive compounds, endothelin-1 (ET-1), bradykinin (BK), and substance P (SP) was measured isometrically in an isolated tissue bath. The effects of a cyclooxygenase inhibitor, indomethacin (10(-5) M) and an inhibitor of nitric oxide production, N omega-Nitro L-Arginine (L-NNA: 3 x 10(-4) M) were determined during agonist-mediated responses. Indomethacin alone markedly enhanced vascular contraction produced by ET-1, while L-NNA did not. Inhibition of endothelium-derived nitric oxide synthesis by L-NNA, however, significantly attenuated BK- and SP-induced vascular relaxations, whereas indomethacin had slight influence. The potentiation between indomethacin and L-NNA in regulating vasomotor tone was not observed in this vascular bed. Thus, it appeared that both the cyclooxygenase and endothelium-derived nitric oxide pathways participated in modifying vascular reactivity. Domination of one pathway over the other depended upon the agonist used to stimulate vascular tissue.     

Site and query scheduling policies in multicomputer databasesystems

We study run-time issues, such as site allocation and query scheduling policies, in executing read-only queries in a hierarchical, distributed memory, multicomputer system. The particular architecture considered is based on the hypercube interconnection. The data are stored in a base cube, which is controlled by a control cube and host node hierarchy. Input query trees are transformed into operation sequence trees, and the operation sequences become the units of scheduling. These sequences are scheduled dynamically at run-time. Algorithms for dynamic site allocation are provided. Several query scheduling policies that support interquery concurrency are also studied. Average query completion times and initiation delays are obtained for the various policies using simulations     

Evaluation of a parallel branch-and-bound algorithm on a class ofmultiprocessors

We propose and evaluate a parallel “decomposite best-first” search branch-and-bound algorithm (dbs) for MIN-based multiprocessor systems. We start with a new probabilistic model to estimate the number of evaluated nodes for a serial best-first search branch-and-bound algorithm. This analysis is used in predicting the parallel algorithm speed-up. The proposed algorithm initially decomposes a problem into N subproblems, where N is the number of processors available in a multiprocessor. Afterwards, each processor executes the serial best-first search to find a local feasible solution. Local solutions are broadcasted through the network to compute the final solution. A conflict-free mapping scheme, known as the step-by-step spread, is used for subproblem distribution on the MIN. A speedup expression for the parallel algorithm is then derived using the serial best-first search node evaluation model. Our analysis considers both computation and communication overheads for providing realistic speed-up. Communication modeling is also extended for the parallel global best-first search technique. All the analytical results are validated via simulation. For large systems, when communication overhead is taken into consideration, it is observed that the parallel decomposite best-first search algorithm provides better speed-up compared to other reported schemes     

Partitioned encoding schemes for algorithm-based fault tolerance inmassively parallel systems

Considers the applicability of algorithm based fault tolerance (ABET) to massively parallel scientific computation. Existing ABET schemes can provide effective fault tolerance at a low cost For computation on matrices of moderate size; however, the methods do not scale well to floating-point operations on large systems. This short note proposes the use of a partitioned linear encoding scheme to provide scalability. Matrix algorithms employing this scheme are presented and compared to current ABET schemes. It is shown that the partitioned scheme provides scalable linear codes with improved numerical properties with only a small increase in hardware and time overhead