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Biomedical subjects

A Prince

Publications and source records attributed to A Prince.

At least 37 records · Page 2Linked to original sources
PubMed1998

Sexual behaviors and safer sex practices of college students on a commuter campus.

The sexual behaviors and safer sex practices of college students at a midwestern commuter university are described. Responses from a student sample of 1,919 indicated that slightly more than 10% used condoms consistently. The most frequently cited reasons for not using condoms were monogamy (83%) and preferring other forms of birth control (31%). The leading reason for consistent condom use was fear of HIV infection (72%). Approximately 75% indicated they talked with their sexual partners about HIV prevention; women reported communicating significantly more often than men did (p < 0.0001). Seventy percent of the sample reported they had only one sexual partner during the past year. Students who had multiple partners during the past year were more likely to practice such unsafe sexual practices as not using condoms and not communicating about HIV prevention. Unsafe sexual practices occur on nontraditional university campuses just as frequently as they do on more traditional campuses, thus supporting the need for HIV prevention programs on every college and university campus.

Adolescent↗
PubMed1998

Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa strains are opportunistic pathogens associated with infections in immunocompromised hosts and patients with cystic fibrosis. Like many other mucosal pathogens, P. aeruginosa cells express flagella which provide motility and chemotaxis toward preferred substrates but also provide a ligand for clearance by phagocytic cells. We tested the role of flagella in the initial stages of respiratory tract infection by comparing the virulence of fliC mutants in a neonatal mouse model of pneumonia. In the absence of fliC, there was no mortality, compared with 30% mortality attributed to the parental strain PAK or 15% mortality associated with infection due to a pilA mutant PAK/NP (P < 0.0001). The fliC mutants caused pneumonia in only 25% of the mice inoculated, regardless of whether there was expression of the pilus, whereas the parental strain was associated with an 80% rate of pneumonia. Histopathological studies demonstrated that the fliC mutants caused very focal inflammation and that the organisms did not spread through the lungs as seen in infection due to either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory response in the mouse lung. 125I-labeled flagellin bound to the glycolipids GM1 and GD1a and to asialoGM1 in an in vitro binding assay. However, flagellin-mediated binding to epithelial gangliosides was a relatively unusual event, as quantified by binding assays of wild-type or fliC mutant organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla+ organisms but not fliC mutants were efficiently taken up by murine macrophages. P. aeruginosa flagella are important in the establishment of respiratory tract infection and may act as a tether in initial interactions with epithelial membranes. This function is offset by the contribution of flagella to host clearance mechanisms facilitating phagocytic clearance and the role of flagellar genes in mucin binding and clearance.

Animals↗
PubMed1998

Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells.

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), particularly the common DeltaF508 mutation, have been associated with alterations in glycolipid sialylation and the availability of receptors for Pseudomonas aeruginosa binding. The surface properties of 9HTEo- tracheal epithelial cell lines transfected with plasmids that overproduce the regulatory (R) domain of CFTR (pCEP-R) and lack cyclic adenosine monophosphate-stimulated Cl- conductance were compared with control cell lines with normal CFTR function. There was increased bacterial adherence to the mutant cell lines with abnormal CFTR activity. Cell lines with overexpression of the R domain had surface properties similar to cells expressing the common DeltaF508 mutation in CF. P. aeruginosa adherence correlated with the increased numbers of asialoGM1 residues available on the surface of the epithelial cells with altered CFTR function; and antibody to asialoGM1, a P. aeruginosa pilin receptor, was able to compete with piliated bacteria for epithelial binding sites. The pCEP-R cell lines with increased bacterial binding were also associated with increased production of interleukin-8 in response to adherent P. aeruginosa compared with cells transfected with the empty vector pCEP. P. aeruginosa pil mutants that lack the adhesin specific for the asialoGM1 receptor did not discriminate between epithelial cells with normal or deficient CFTR function. These results confirm a direct relationship between aberrant CFTR function and increased levels of apical asialoGM1, and support the role of these asialylated glycolipids as P. aeruginosa receptors that initiate an epithelial proinflammatory response in response to bacterial ligands.

Bacterial Adhesion↗
PubMed1997

Optimality: from neural networks to universal grammar.

Can concepts from the theory of neural computation contribute to formal theories of the mind? Recent research has explored the implications of one principle of neural computation, optimization, for the theory of grammar. Optimization over symbolic linguistic structures provides the core of a new grammatical architecture, optimality theory. The proposition that grammaticality equals optimality sheds light on a wide range of phenomena, from the gulf between production and comprehension in child language, to language learnability, to the fundamental questions of linguistic theory: What is it that the grammars of all languages share, and how may they differ?

Adult↗
PubMed1997

Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease.

An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a Cl ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyr-phostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

Benzylidene Compounds↗
PubMed1997

Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator.

Burkholderia cepacia is recognized as an important pathogen in the lung infections of patients with cystic fibrosis. An inducible beta-lactamase activity has been associated with increased resistance to beta-lactam antibiotics in clinical isolates of B. cepacia. In this study, we report the revised sequence of the penA gene, which encodes the inducible penicillinase of B. cepacia, and show that it belongs to the molecular class A beta-lactamases and exhibits a high degree of similarity to the chromosomal beta-lactamase of Klebsiella oxytoca. Analysis of the nucleotide sequence of the DNA region directly upstream of the penA coding sequence revealed an open reading frame (penR), the transcription of which was oriented opposite to that of penA and whose initiation was 130 bp away from that of penA. Two potential ribosome-binding sites and two overlapping -10 and -35 promoter sequences were identified in the intercistronic region. The predicted translation product of penR was a polypeptide of 301 amino acids with an estimated molecular size of 33.2 kDa. The deduced polypeptide of penR showed a high degree of similarity with AmpR-like transcriptional activators of class A and C beta-lactamases, with identities of 59 and 58.7% with Pseudomonas aeruginosa PAO1 AmpR and Proteus vulgaris B317 CumR, respectively. The N-terminal portion of B. cepacia PenR was predicted to include a helix-turn-helix motif, which may bind the LysR motif identified in the intercistronic region. Induction of PenA by imipenem was shown to be dependent upon the presence of PenR. Expression of the cloned B. cepacia penA and penR genes in Escherichia coli SNO302 (ampD) resulted in a high basal and hyperinducible PenA activity. These results suggest that the regulation of the PenA penicillinase of B. cepacia 249 is similar to that observed in other class A and class C beta-lactamases that are under the control of a divergently transcribed AmpR-like regulator.

Amino Acid Sequence↗
PubMed1996

Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation.

Chronic lung disease caused by antibiotic-resistant Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is difficult to treat, especially in those who are lung transplantation candidates. Analysis of antibiotic susceptibility and synergy studies of 1,296 isolates revealed that 172 (13.3%) were multiply resistant (i.e., resistant to two or more classes of anti-Pseudomonas agents). beta-Lactam agents (including imipenem and aztreonam) or aminoglycosides inhibited only 11% of the multiply resistant strains, while ciprofloxacin inhibited 34%. High concentrations of tobramycin and gentamicin (200 micrograms/mL), achievable by aerosol administration, inhibited 95% of isolates and overwhelmed permeability-resistance mechanisms. Antimicrobial pairs tested in checkerboard dilutions of clinically achievable drug concentrations inhibited 75% of the multiply resistant strains. On average, three additive and 2.4 synergistic pairs of antimicrobial agents had activity per strain. Transplantation candidates were older than nontransplantation candidates (P = .034), and isolates from transplantation candidates were less likely to be inhibited by antibiotic combinations (P < .001). Administration of aerosolized aminoglycosides and synergy testing of antimicrobial combinations may represent viable therapeutic options for patients with CF.

Adolescent↗
PubMed1996

Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection.

We sought to identify which Pseudomonas aeruginosa products are involved initiating respiratory tract infection. Defined mutants derived from strain PAO i.e., PAOR1 (lasR),PAO-pmm (algC) (an LPS mutant), and AK1152 (which is Fla- and lacks functional pili), were significantly less virulent than PAO1 in a BALBc/ByJ neonatal mouse model of infection as measured by their abilities to cause acute pneumonia, bacteremia, and death. All three mutants were also less adherent to epithelial cells in an in vitro binding assay. PAOR1 and AK1152 were less able to elicit epithelial production of interleukin-8 than PAO1. LasR was found to be required for the optimal expression of neuraminidase under conditions of increased osmolarity, as might be present in certain pathological conditions. PAO-exsA::omega,, which lacks exoenzyme S expression, was fully virulent, causing at least as much pathology as PAO1. The expression of several P. aeruginosa virulence factors appears to be required to establish pulmonary infection in the neonatal mouse.

Animals↗
PubMed1995

Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface.

Chronic colonization and infection of the lung with Pseudomonas aeruginosa is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. We found that polarized CF bronchial and pancreatic epithelia bound P. aeruginosa in a reversible and dose-dependent manner. There was significantly greater binding to CF bronchial and pancreatic cells than to their matched pairs rescued with the wild-type CF transmembrane conductance regulator. Bound P. aeruginosa were easily displaced by unlabeled P. aeruginosa but not by Escherichia coli, an organism that does not cause significant pulmonary disease in CF. In contrast, Staphylococcus aureus, a frequent pathogen in CF, could effectively displace bound P. aeruginosa from its receptor. We found undersialylation of apical proteins and a higher concentration of asialoganglioside 1 (aGM1) in apical membranes of CF compared with rescued epithelia. Incubation of P. aeruginosa with aGM1 reduced its binding, as did treatment of the epithelia with the tetrasaccharide moiety of this ganglioside (Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc). Finally, an antibody to aGM1 effectively displaced P. aeruginosa from its binding site and blocked binding of S. aureus to CF cells but not to rescued cells. These results show that the tetrasaccharide of aGM1 is a receptor for P. aeruginosa and S. aureus and that its increased abundance in the apical membrane of CF epithelia makes it a likely contributor to the pathogenesis of bacterial infections in the CF lung.

Bacterial Adhesion↗
PubMed1995

Treatment of intractable gastrointestinal manifestations of chronic granulomatous disease with cyclosporine.

Gastrointestinal manifestations of chronic granulomatous disease of childhood include granulomatous inflammatory bowel disease. Severe colitis and perirectal disease developed in a 12-year-old boy with chronic granulomatous disease while he was receiving interferon gamma therapy. The boy had a deficiency of the 22 kd light chain of the cytochrome b heterodimer. After conventional medical therapy proved to be ineffective, a rapid clinical response was obtained to cyclosporine.

Aspergillus fumigatus↗
PubMed1995

Binding of Pseudomonas aeruginosa to respiratory epithelial cells from patients with various mutations in the cystic fibrosis transmembrane regulator.

OBJECTIVE: To determine whether there is an association between mutations of the cystic fibrosis transmembrane regulator (CFTR) and the predilection of patients with cystic fibrosis (CF) for Pseudomonas aeruginosa infection. METHOD: We quantified the adherence of P. aeruginosa PA01, labeled with sulfur 35-methionine, to epithelial monolayers derived from nasal scrapings of patients with specific CFTR mutations, and of carriers and normal subjects. RESULTS: Adherence of P. aeruginosa to epithelial cells from patients with CF was significantly greater than to cells from either carriers (t = 2.94; p = 0.009) or normal subjects (t = 3.32; p = 0.004). Adherence to epithelial cells from patients with CF who were homozygous for the delta F508 mutation ranged from 12% to 35% (mean, 23.7%) of the added inoculum, which was significantly greater than the binding to cells from patients with other mutations, which ranged from 3% to 18% (mean, 9.4%; t = 3.71; p = 0.002), from heterozygote carriers (3% to 11%; mean, 7.9%; t = 4.87; p = 0.002), or from normal subjects (2% to 10%: mean, 7.0%; t = 5.21; p = 0.002). CONCLUSION: Adherence to P. aeruginosa can be correlated with homozygosity for the delta 508 mutation; CFTR dysfunction may be one of the factors involved in the pathogenesis of pulmonary infection in CF.

Adolescent↗
PubMed1995

Role of Pseudomonas aeruginosa pili in acute pulmonary infection.

The role of piliation in the development and course of acute pulmonary infection was examined using infant BALB/cByJ mice inoculated by intranasal instillation of isogenic Pil+ and Pil- mutants of Pseudomonas aeruginosa PA1244, PAK, and PAO1. The piliated strains caused more cases of pneumonia, bacteremia, and mortality than the nonpiliated strains (chi-square analysis, alpha = 0.001). The piliated strains were more often associated with severe diffuse pneumonias, while the nonpiliated organisms resulted in less severe, focal pneumonias, although these differences did not achieve statistical significance. Purified pilin protein used to inoculate the mice resulted in local inflammatory changes. The nonpiliated strain PA1244-NP was as virulent as the piliated strain PAO1, suggesting that expression of other virulence factors are also important in the development of acute pneumonia. This infant mouse model of pulmonary infection appears to be a useful system for the analysis of P. aeruginosa virulence factors involved in the pathogenesis of pneumonia.

Animals↗
PubMed1995

Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8.

Respiratory epithelial cells play a crucial role in the inflammatory response during Pseudomonas aeruginosa infection in the lungs of patients with cystic fibrosis. In this study, we determined whether the binding of specific Pseudomonas gene products (pilin, flagellin) to their receptors on respiratory epithelial cells would result in production of the neutrophil chemoattractant IL-8. Piliated wild-type organisms, purified pili, or antibody to the pilin receptor (asialoGM1) evoked significant production of IL-8 by immortalized airway epithelial cells, whereas nonpiliated organisms were less able to bind to respiratory epithelial cells and stimulated much less IL-8 secretion (P < 0.01). A piliated, nonflagellated strain was also associated with decreased binding and a diminished level of IL-8 production when compared to wild-type organisms. Isogenic, nonadherent rpoN mutants, lacking pilin and flagellin, did not bind or elicit an IL-8 response. In addition, the IL-8 response was four-fold higher in a cystic fibrosis cell line compared with its corrected cell line. The Pseudomonas autoinducer, an exoproduct secreted during chronic infection, was found to stimulate IL-8 in a dose-dependent manner. P. aeruginosa adhesins, which are necessary for initial infection, directly stimulate IL-8 production by respiratory epithelial cells and therefore play a major role in the pathogenesis of Pseudomonas infection in patients with cystic fibrosis. The inflammatory response is subsequently perpetuated by Pseudomonas autoinducer which is secreted during chronic infection.

Adhesins, Bacterial↗
PubMed1995

The measurement of team process.

The construct validity of measures of team process was evaluated using predictive, known groups and multitrait-multimethod (MTMM) validation strategies. Military air crews (N = 51) flew two simulated missions. Independent judges provided evaluations of the same six team process variables in both scenarios. An MTMM analysis of judges' ratings treating judges as a method variable showed good convergent and discriminant validity. Judges' mean ratings of the six process variables were correlated with mission effectiveness. Some process measures discriminated between student and instructor teams, thus showing discrimination between known groups. Conversely, an MTMM analysis of ratings treating scenarios as a method showed poor convergent validity. We concluded that important team process behaviors have been identified and can be rated validly but that multiple observations are necessary to assess characteristics of individual teams with any accuracy. The discussion includes implications for practice and future research.

Aircraft↗
PubMed1993

Pediatric infective endocarditis in the modern era.

Sixty-two cases of endocarditis occurring in children between January 1977 and February 1992 were reviewed and compared with series from the 1970s and early 1980s. Changes in risk factors, pathogens, diagnostic modalities, and outcome were determined. Complex congenital heart disease (22 cases) and unrepaired ventricular septal defect (9 cases) were the most common underlying lesions. A total of 19 children with normal anatomy had endocarditis; 6 had community-acquired infection and 13 had hospital-acquired endocarditis (11 of these 13 children had central venous catheters in place, including 7 premature infants). Echocardiograms revealed vegetations in 25 of 49 patients; 24 of these patients had positive echocardiographic findings on the first study. Echocardiographic findings were most often negative in children with complex cyanotic heart disease. Staphylococcus aureus (39%) was the most common pathogen isolated and was associated with a higher incidence of central nervous system complications (p < 0.0015) and a greater need for surgical intervention (p = 0.01) than were other pathogens. Methicillin-resistant S. aureus (eight cases) and coagulase-negative staphylococci (three cases) emerged as important pathogens but were not associated with increased morbidity or mortality rates. Fungal endocarditis (six cases) had a 67% mortality rate. Overall the mortality rate was 11%. Endocarditis remained undiagnosed in seven seriously ill patients until postmortem examination. This study indicates that, during the past decade, important changes in risk factors, pathogens, and the susceptible population have altered the presentation and management of endocarditis in children.

Adolescent↗
PubMed1993

Bilateral discoid medial menisci: a case report and literature review.

The purpose of this article is to present the fourth case report of bilateral discoid medial menisci. A previously unreported anomaly of the tibial plateaus associated with the discoid menisci was also present bilaterally. The patient was treated successfully by excision of the central anomalous discoid portion of the menisci, using arthroscopic techniques.

Adult↗