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Y Schlesinger

Publications and source records attributed to Y Schlesinger.

47 records · Page 3Linked to original sources
PubMed1994

Synthesis and characterization of photoactivatable peptide agonists of the human thrombin receptor.

Chemical synthesis and biochemical analysis of modified agonist peptides of the human thrombin receptor derived from the sequence SFLLRNP containing photoactivatable azido groups and biotin for sensitive detection is described. Substitution of leucine in position three with p-azidophenylalanine and extension of the C-terminus with a KGGK spacer containing biotin covalently linked to the side chain of the C-terminal lysine residue resulted in an active receptor agonist as determined by intracellular Ca2+ mobilization in human erythroleukemia (HEL) cells. In contrast, substitution of phenylalanine in position two with p-azidophenylalanine reduced agonist activity significantly.

Amino Acid Sequence↗
PubMed1994

Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management.

STUDY OBJECTIVE: To evaluate the performance characteristics and potential clinical utility of a polymerase chain reaction (PCR) assay for enteroviral RNA in comparison to viral culture in infants under 3 months of age with meningitis. SPECIMENS AND TESTING: Specimens were obtained from a collection of cerebrospinal fluid specimens from infants under 3 months of age (excluding those in the neonatal intensive care unit) undergoing lumbar puncture at St. Louis Children's Hospital during a 12-month period. Those tested by PCR included all 27 with pleocytosis, 8 others from infants without pleocytosis but from whom an enterovirus was cultured, and 10 from infants who did not have pleocytosis and had a negative viral culture of cerebrospinal fluid. Viral cultures were performed at the discretion of physicians caring for individual patients. RESULTS: PCR was positive for enteroviral RNA on cerebrospinal fluid (CSF) specimens from 11 of 12 patients with definite or probable enteroviral meningitis, as well as on 6 of 13 with possible enteroviral meningitis, and was negative on all 10 with absence of pleocytosis and negative enteroviral cultures. CSF viral cultures were negative in 6 of the patients in whom PCR was positive. Viral cultures had minimal impact on patient management. In contrast, under study assumptions, PCR could have saved an average of 1.2 days of hospitalization per patient in the 27 patients with CSF pleocytosis. CONCLUSIONS: Enterovirus PCR performed on CSF is a sensitive and specific method for the diagnosis of enteroviral meningitis. This method has the potential for improving the accuracy of diagnosis in young infants and for saving costs by allowing earlier diagnosis and discharge from the hospital when clinically appropriate.

Cerebrospinal Fluid↗
PubMed1993

A peptide ligand of the human thrombin receptor antagonizes alpha-thrombin and partially activates platelets.

The peptide YFLLRNP antagonizes the aggregation of human platelets when induced by low concentrations of alpha-thrombin or the thrombin receptor agonist peptide (SFLLRNP), demonstrating that it interacts specifically with the thrombin receptor. Platelets exposed to YFLLRNP show immediate shape change (pseudopod formation) and potentiation of the ADP and platelet-activating factor response, but no Ca2+ mobilization, P47 (pleckstrin) phosphorylation, secretion, or aggregation. Thus, YFLLRNP induces a state of partial activation of the platelets. Furthermore, with platelets prestimulated with adrenalin (10 microM), YFLLRNP induces aggregation, but no secretion, and only in the presence of added fibrinogen. We also found that prostacyclin inhibits the YFLLRNP-induced shape change; but EDTA, aspirin, and apyrase (ADP scavenger) do not. Thus, the thrombin receptor in platelets may communicate, independently of Ca2+ mobilization and P47 phosphorylation (protein kinase C activation), with intracellular signaling mechanisms that 1) modulate the cytoskeleton structure, 2) potentiate other platelet responses, and 3) stimulate coupling between the thrombin receptor and fibrinogen binding (the glycoprotein IIb-IIIa complex). YFLLRNP may be useful for differentiating between several possible activation states of the platelet thrombin receptor.

Amino Acid Sequence↗
PubMed1992

Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines. The Vaccine Study Group.

OBJECTIVE: Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen. In this study, we compared the avidity of antibodies elicited by vaccination with three Haemophilus influenzae type b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity. DESIGN: A convenience sample of 171 postvaccination serum samples with more than 0.5 microgram/mL of anticapsular antibody, the minimum concentration required for measurement of avidity. The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM197 (Oligo-CRM). PATIENTS: Healthy infants recruited in private practices. PRIMARY OUTCOME MEASURES: Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers. RESULTS: In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (P less than .001). The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (P less than .02) but higher than PRP-OMPC (P = .001). Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (P less than .001). Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM-1 or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM-1 or less. Antibodies with avidity of 1.25 nM-1 or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM-1 or greater (P less than .001). CONCLUSIONS: Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays. Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease.

Antibodies, Bacterial↗
PubMed1991

cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization.

The serine protease alpha-thrombin (thrombin) potently stimulates G-protein-coupled signaling pathways and DNA synthesis in CCL39 hamster lung fibroblasts. To clone a thrombin receptor cDNA, selective amplification of mRNA sequences displaying homology to the transmembrane domains of G-protein-coupled receptor genes was performed by polymerase chain reaction. Using reverse transcribed poly(A)+ RNA from CCL39 cells and degenerate primers corresponding to conserved regions of several phospholipase C-coupled receptors, three novel putative receptor sequences were identified. One corresponds to an mRNA transcript of 3.4 kb in CCL39 cells and a relatively abundant cDNA. Microinjection of RNA transcribed in vitro from this cDNA in Xenopus oocytes leads to the expression of a functional thrombin receptor. The hamster thrombin receptor consists of 427 amino acid residues with 8 hydrophobic domains, including one at the extreme N-terminus that is likely to represent a signal peptide. A thrombin consensus cleavage site is present in the N-terminal extracellular region of the receptor sequence followed by a negatively charged cluster of residues present in a number of proteins that interact with the anion-binding exosite of thrombin.

Amino Acid Sequence↗
PubMedDate not supplied

Kingella kingae endocarditis in a child with hair-cartilage hypoplasia.

Abstract. Kingella kingae is a fastidious Gram-negative rod that since the 1980s has been appreciated as a cause of a variety of human infections, including bone and joint infections, bacteremia, and rarely endocarditis [2, 6, 7, 9]. K. kingae endocarditis is rare, and only a few cases occur in normal, native valves. We report a case of K. kingae endocarditis in a patient with hair-cartilage hypoplasia who had previously undergone bone marrow transplantation. The combination of these rare conditions is discussed.

Adolescent↗
PubMedDate not supplied

Comparison of peritoneal fluid culture results from adults and children undergoing CAPD.

BACKGROUND: Peritonitis is a common complication in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). Empirical treatment is based on the organisms that are most frequently isolated and their susceptibilities. OBJECTIVE: To analyze and then compare peritoneal fluid culture results from adult and pediatric patients on CAPD, with respect to micro-organisms and antimicrobial susceptibilities. DESIGN: Three-year retrospective review of peritoneal fluid cultures from adults and children on CAPD. RESULTS: We isolated 481 organisms from 378 peritoneal fluid specimens, collected from 135 patients (45 children, 90 adults). There were 191 episodes of peritonitis in children (mean 4.2+/-3.5, range 1 - 15) compared to 187 in adults (2.1+/-1.9, range 1 - 10) (p< 0.001). Two or more episodes occurred in 30 of 45 children (67%) compared to 33 of 90 adults (37%) (p < 0.001).The number of different organisms/patient as well as the total number of isolates/patient were significantly greater in children (respectively, 2.8+/-2.3, range 1 - 12; and 5.3+/-5.2, range 1 - 27) than in adults (2.0+/-1.3, range 1 - 6; and 2.7+/-2.4, range 1 - 10) (p< 0.005). After Staphylococcus epidermidis, S. aureus was the most frequently isolated organism, occurring in 18% of episodes in adults and 12% of episodes in children (p< 0.01). Twenty-two of 33 fungal isolates (67%) in children were Candida parapsilosis compared to 3 of 24 (12%) in adults (p < 0.001). Subanalysis of multiple episodes revealed that Pseudomonas and Candida occurred significantly more often in children (p< 0.01), whereas S. aureus occurred more often in adults (p< 0.001). In polymicrobial episodes S. epidermidis occurred more often in adults (p < 0.05). Significant differences in susceptibilities to ampicillin, ceftriaxone, chloramphenicol, and gentamicin were found between children and adults (p< 0.05 - 0.001). CONCLUSIONS: CAPD-associated peritonitis occurs significantly more often in children than adults. Significant differences in microbial etiology and susceptibilities were found between pediatric and adult patients. Each dialysis unit should periodically analyze peritoneal fluid culture results from its CAPD patients. These data can then be used for optimization of empirical antimicrobial therapy of peritonitis.

Adult↗