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.     

Proving termination of GHC programs

A transformational approach for proving termination of parallel logic programs such as GHC programs is proposed. A transformation from GHC programs to term rewriting systems is developed; it exploits the fact that unifications in GHC-resolution correspond to matchings. The termination of a GHC program for a class of queries is implied by the termination of the resulting rewrite system. This approach facilitates the applicability of a wide range of termination techniques developed for rewrite systems in proving termination of GHC programs. The method consists of three steps: (a) deriving moding information from a given GHC program, (b) transforming the GHC program into a term rewriting system using the moding information, and finally (c) proving termination of the resulting rewrite system. Using this method, the termination of many benchmark GHC programs such as quick-sort, merge-sort, merge, split, fair-split and append, etc., can be proved. This is a revised and extended version of Ref. 12). The work was partially supported by the NSF Indo-US grant INT-9416687 Kapur was partially supported by NSF Grant nos. CCR-8906678 and INT-9014074. M. R. K. Krishna Rao, Ph.D.: He currently works as a senior research fellow at Griffith University, Brisbane, Australia. His current interests are in the areas of logic programming, modular aspects and noncopying implementations of term rewriting, learning logic programs from examples and conuterexamples and dynamics of mental states in rational agent architectures. He received his Ph.D in computer science from Tata Institute of Fundamental Research (TIFR), Bombay in 1993 and worked at TIFR and Max Planck Institut für Informatik, Saarbrücken until January 1997. Deepak Kapur, Ph.D.: He currently works as a professor at the State University of New York at Albany. His research interests are in the areas of automated reasoning, term rewriting, constraint solving, algebraic and geometric reasoning and its applications in computer vision, symbolic computation, formal methods, specification and verification. He obtained his Ph.D. in Computer Science from MIT in 1980. He worked at General Electric Corporate Research and Development until 1987. Prof. Kapur is the editor-in-chief of the Journal of Automated Reasoning. He also serves on the editorial boards of Journal of Logic Programming, Journal on Constraints, and Journal of Applicable Algebra in Engineering, Communication and Computer Science. R. K. Shyamasundar, Ph.D.: He currently works as a professor at Tata Institute of Fundamental Research (TIFR), Bombay. His current intersts are in the areas of logic programming, reactive and real time programming, constraint solving, formal methods, specification and verification. He received his Ph.D in computer science from Indian Institute of Science, Bangalore in 1975 and has been a faculty member at Tata Institute of Fundamental Research since then. He has been a visiting/regular faculty member at Technological University of Eindhoven, University of Utrecht, IBM TJ Watson Research Centre, Pennsylvania State University, University of Illinois at Urbana-Champaign, INRIA and ENSMP, France. He has served on (and chaired) Program Committees of many International Conferences and has been on the Editorial Committees.     

Muscle transformation of the sartorius muscle in a canine model: clinical impact for electrodynamic graciloplasty as a "neosphincter"

PURPOSE: Transformation of fast-twitching skeletal muscles to slow-twitching, slowly fatigable muscles has become of clinical interest in the recent past. Transposition and transformation of the gracilis muscle to use it as a substitute for a resected or defected anal sphincter (graciloplasty) have been reported as achieving promising results in the treatment of fecal incontinence caused by sphincter defects or following abdominoperineal anorectal excision for cancer. METHOD: This experimental study used a canine model and the sartorius muscle to evaluate the functional efficiency of two different configurations of the muscle loop to compare the presently applied transformation program (8 weeks) with a shorter (5 weeks) protocol. In six beagle dogs, both sartorius muscles were wrapped around two stomas, either in an alpha fashion or in the so-called split-sling technique. Muscle transformation was achieved by controlled neuromuscular stimulation either during eight (Program A) or five weeks (Program B). After completion of the transformation period, the function of the muscle slings was evaluated by manometry, and histomorphologic evaluation of the sartorius muscles was performed. RESULTS: It was shown that muscle transformation led to a slowly fatigable muscle that made it possible to perform continuos (tetanic) contraction, regardless of the configuration or the duration of the transformation. Median pressures created by these muscles also did not differ significantly. In accordance with these functional findings, the histologic evaluation showed the typical, significant increase of Type I fibers in both muscle slings and following both transformation protocols. Although the decrease of fast-twitching Type II fibers was more pronounced following the conventional (8 weeks) program, this finding did not influence the functional results. CONCLUSIONS: Results of our experiment indicate the possibility for using a shorter transformation protocol for transformation of the gracilis muscle during graciloplasty in the clinical setting. Furthermore, the efficacy and safety of the modified (split-sling) wrap technique was demonstrated.     

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.     

Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts

Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro.     

Visual impairment in Swedish children. III. Diagnoses

PURPOSE: To gain an overview of the spectrum of diagnoses among Swedish visually impaired children. METHODS: An epidemiological study of all known visually impaired children was made by review of medical records. RESULTS AND CONCLUSION: In all we found 2373 children, 0-19 years of age, with an age-specific prevalence of 10.9/10,000. The two largest diagnostic groups included neuro-ophthalmological and retinal diseases. The most frequent disorders were cerebral visual impairment, non-hereditary optic atrophy, retinal dystrophy (when regarded as a general entity), congenital hypoplasia of the optic nerve and congenital cataract. Nystagmus secondary to brain disorder, albinism, congenital nystagmus, retinopathy of prematurity and high myopia were also found in a considerable number of patients. The leading diagnoses in children with WHO-defined childhood blindness were non-hereditary optic atrophy, cerebral visual impairment and retinopathy of prematurity. A large proportion of the children, especially in the groups with neuro-ophthalmological disorders and malformations of the posterior segment had additional impairments, emphasizing the importance of a multi-disciplinary approach when assessing multi-handicapped children.     

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.