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Biomedical subjects

J Bargon

Publications and source records attributed to J Bargon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Risk of Pseudomonas aeruginosa cross-colonisation in patients with cystic fibrosis within a holiday camp--a molecular-epidemiological study.

OBJECTIVE: A study on the molecular epidemiology of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) from Germany (N = 18) and Israel (N = 12) is presented. The aim is to provide an answer to the question as to whether or not social contact outside the hospital environment involves a potential risk for person-to-person spread of this pathogen. METHODS: Sputa from German and Israeli patients were obtained while these were attending a holiday camp in Israel. The sputum samples were analysed with regard to Pseudomonas aeruginosa. Strains dissimilar in macroscopic appearance and/or antibiotic resistance patterns were genotyped using pulsed-field gel electrophoresis after digestion of genomic DNA with restriction endonuclease Spel. The genetic polymorphism of DNA fragment patterns of all strains (N = 146) was studied for their overall relatedness using a fingerprint software system. RESULTS: Most of the German patients (77.7%) were colonised persistently by a unique clonal type during the four-week screening period. Isolates obtained from Israeli patients displayed a very close clonal relationship and a higher antibiotic resistance as a result of preceding epidemic spread of certain clones before the camp. Additionally, isolates showing identical PFGE patterns were demonstrated once in a single male Israeli patient and in one female German patient, suggesting previous cross-colonisation. CONCLUSION: The occurrence of person-to-person spread through social contact in patients with CF is supported by our findings, but remains a rare event outside the hospital environment, provided appropriate hygienic measures are applied.

Adult↗
PubMed2000

Mechanistic aspects of dihydrogen activation and transfer during asymmetric hydrogenation in supercritical carbon dioxide.

A new "CO2-philic" chiral rhodium diphosphinite complex was synthesized and applied as catalyst precursor in the asymmetric hydrogenation of dimethyl itaconate in scCO2, scC2H6 and various liquid organic solvents. Deuterium labeling studies and parahydrogen-induced polarization (PHIP) NMR experiments were used to provide the first detailed mechanistic insight into the activation and transfer of the dihydrogen molecule during hydrogenation in scCO2. Chemical interactions between CO2 and reactive intermediates of the catalytic pathway could be excluded as possible explanations for the experimentally verified difference in the catalytic behavior in scCO2 and hexane.

Carbon Dioxide↗
PubMed2000

Finite-difference approach for the high-precision analysis of rotating-frame diffusion images

A finite-difference approach has been developed for precisely determining diffusion coefficient and T(1) relaxation time in fluid samples analyzed by magnetization-grating rotating-frame imaging (MAGROFI) with either a surface coil or a toroid cavity detector (TCD). This approach avoids shortcomings of phenomenologically based approximations, such as neglect of sample geometries with singularities at the confines of the sample volume, and accounts for the diffusive edge enhancement observed in fluid imaging. Error limits are discussed. The new method has been applied to the determination of the self-diffusion coefficient for MAGROFI experiments using TCDs filled with acetone. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Differential expression of human alpha- and beta-defensins mRNA in gastrointestinal epithelia.

BACKGROUND: While defensins have received great attention for their role in bronchial innate immune defence, little is known about the expression levels of the four human epithelial defensins (HD5, HD6, hBD1 and hBD2) in the digestive tract. In this study we quantified the alpha- and beta-defensins mRNA in biopsies obtained from the gastrointestinal mucosa and identified the cells expressing the beta-defensin hBD1 mRNA in ileal mucosa. MATERIAL AND METHODS: Biopsies from human stomach (corpus and antrum), duodenum, jejunum, ileum and colon were analysed for their expression of alpha- and beta-defensins. The mRNA of defensins was quantified by semiquantitative reverse transcription-polymerase chain reaction. Cells expressing beta-defensin hBD1 mRNA were identified by in situ hybridization with 35S-labelled RNA probes in tissue sections of human ileum. RESULTS: The hBD1 mRNA was expressed at low levels with little variability throughout the gastrointestinal tract and was detected in all epithelial cells of ileal mucosa. HD5 and HD6 mRNA expression was restricted to the intestine and displayed high interindividual variability. The highest expression levels were observed in jejunum and ileum. Biopsies obtained from duodenum displayed low levels or no expression of HD5 and HD6. The expression level increased considerably in a biopsy obtained from a patient with acute coeliac sprue. In contrast, low levels were observed in a biopsy from a patient with coeliac sprue in remission. CONCLUSIONS: The expression levels of hBD1, HD5 and HD6 throughout the gastrointestinal tract are tissue and peptide specific and these defensins are expressed with high interindividual variability.

Anti-Infective Agents↗
PubMed2000

Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells.

BACKGROUND/AIMS: Human defensins are antibiotic peptides expressed in myeloid and epithelial cells. Human alpha-defensin 5 (HD5) has been detected in Paneth cell granules in the crypts of Lieberkühn and has recently been identified in the female reproductive tract. The aim of this study was to investigate the presence of HD5 mRNA in nasal and bronchial epithelial cells. METHODS/RESULTS: Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that HD5 mRNA was expressed infrequently and to varying degrees in bronchial and nasal epithelial cells. In situ hybridisation resulted in a positive signal in the epithelial layer of nasal polyps. HD5 mRNA was locally restricted to a specific area of epithelial cells and also occurred in submucosal glands. CONCLUSIONS: HD5 mRNA expression in nasal and bronchial epithelial cells is rare and seemed to be locally induced. The results indicate that HD5 might play a role in innate defence in nasal and bronchial epithelia.

Base Sequence↗
PubMed1999

Epithelial defensins impair adenoviral infection: implication for adenovirus-mediated gene therapy.

Epithelial cells have been to participate actively in host defense by producing small cationic peptides called defensins. To investigate the biological activity of epithelial defensins in more detail, we expressed two defensins, hBD-1 and HD-5, in eukaryotic cell lines. Defensins were localized in the cytoplasm and in cell culture medium and exhibited strong microbicidal activity toward Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Moreover, our data indicate that the presence of defensins protected the cells from adenoviral infection. The presence of HD-5 or hBD-1 reduced the infectivity of Av1CF2 three- to fivefold. These results imply that defensins must be considered a serious obstacle whenever adenovirus is used to deliver genes to epithelial cells.

Adenoviridae↗
PubMed1999

Mediastinal lymph nodes demonstrated by mediastinal sonography: activity marker in patients with cystic fibrosis.

PURPOSE: To evaluate the potential diagnostic role of mediastinal sonography in patients with cystic fibrosis (CF), we screened the mediastinum of adult CF patients with and without signs of infection and healthy controls. METHODS: Fifty-four consecutive adult patients with CF and 53 healthy volunteers underwent high-resolution mediastinal sonography. The paratracheal region and aorticopulmonary window of each subject were examined for lymph nodes. Each patient was screened for clinical signs of infection. RESULTS: Lymph nodes were detectable in the mediastinum of 39 of 50 CF patients (78%); the mean total lymph node volume was 1.5 +/- 1.7 cm3. Lymph nodes were detectable in the mediastinum of 31 of 50 controls (62%); the mean total lymph node volume in this group was 0.3 +/- 0.3 cm3 (p < 0.001). In the 30 CF patients with signs of infection, the mean total lymph node volume was larger (2.0 +/- 1.8 cm3) than in the 20 CF patients without signs of infection (0.7 +/- 0.9 cm3; p = 0.002). CONCLUSIONS: These results indicate that lymph node volume determination by high-resolution mediastinal sonography may help assess inflammatory activity in patients with CF.

Adolescent↗
PubMed1999

Prophylactic antibiotic therapy is associated with an increased prevalence of Aspergillus colonization in adult cystic fibrosis patients.

Aspergillus colonization is a common phenomenon in adult cystic fibrosis (CF) patients. The clinical significance of Aspergillus for the pathogenesis of CF lung disease remains unclear and factors predisposing to such colonization are still completely unknown. We investigated the prevalence of Aspergillus colonization in 104 adult CF patients who attended our outpatient clinic in 1997. With respect to demographic and clinical data, and antibiotic therapy received, we further examined which factors were associated with Aspergillus colonization in these patients. Repeated investigations of CF sputum samples revealed Aspergillus species in 43/104 (41.3%; 95% confidence interval 30.2-52.5%) of the patients. We found no significant relationship between Aspergillus colonization and age (P > 0.4), gender (P = 0.4), colonization with pseudomonas species (P > 0.6), lower lung function values (P > 0.9), or worse chest radiography (P > 0.1). Surprisingly, the prevalence of Aspergillus colonization was higher in CF patients receiving prophylactic antibiotic therapy (oral antibiotics: P = 0.05; inhalative antibiotics: P = 0.035; both antibiotics: P = 0.048). Prophylactic antibiotics are widely used to eradicate or decrease chronic bronchopulmonary infection in CF. Our results indicate that long-term antibiotic therapy may predispose CF patients to Aspergillus colonization.

Adult↗
PubMed1999

Eosinophilic cationic protein as a marker of nasal inflammation in patients with cystic fibrosis.

OBJECTIVES: Evaluation was made of eosinophilic cationic protein (ECP) in nasal secretion for measuring the degree of nasal inflammation and monitoring response to therapy in cystic fibrosis (CF) patients with chronic rhinosinusitis. Symptoms and findings in regard to ECP levels before and after treatment were described. STUDY DESIGN: Study was prospective, with 21 CF patients aged 4 to 19 years; 20 healthy volunteers served as controls. Collection of nasal secretion by a sponge was performed, and blood samples were obtained for serum. Cystic fibrosis (CF) patients were classified according to nasal symptoms and findings. METHODS: ECP was measured by fluoroimmunoassay. Age, sex, nasal symptoms, and endoscopic and histological findings were obtained, and examinations were conducted before and after treatment; recurrences were recorded. RESULTS: In CF patients with chronic nasal inflammation, increased nasal levels of ECP were detected when compared with asymptomatic CF patients or healthy nonatopic subjects. ECP concentrations were strongly related to the extent of nasal disease; patients with nasal polyps had higher levels than those without. Checked at 1 and 4 months after treatment, ECP levels declined with regression of symptoms, and in patients with exacerbation of nasal disease, ECP levels rose. CONCLUSIONS: According to our study, there is a relationship between levels of ECP in nasal secretions and the degrees of nasal inflammation. In addition, the measurement of ECP could be useful in monitoring nasal disease in CF patients.

Adolescent↗
PubMed1999

Effects of short-term inhaled fluticasone on oxidative burst of sputum cells in cystic fibrosis patients.

Inhaled corticosteroids have been proposed to decrease pulmonary inflammation in cystic fibrosis (CF). In this study the effects of therapy with inhaled fluticasone on clinical and sputum outcomes (leukocyte count, activity of myeloperoxidase, superoxide anion release) in adult CF patients were investigated in an open label design. Twenty-six stable patients (median+/-SD forced expiratory volume in one second (FEV1) 58.1+/-19.9% pred.) were randomly assigned to the study group (500 microg b.i.d., for three weeks) or the control group (n=14; nonsteroid medication). Sputum samples were obtained during inhalation of hypertonic saline (3%, 20 min), which was found not to alter the investigated sputum parameters. No significant changes in clinical parameters, sputum leukocyte count, activity of myeloperoxidase, and baseline superoxide anion release where observed following therapy. Surprisingly, stimulated superoxide anion release increased significantly after therapy (34.1+/-17.7 versus 25.2+/-17.4 nmol x hr(-1) x 10(6) cells, p<0.03) and exceeded spontaneous variability of this parameter (p=0.02 versus control group). In conclusion, in adult cystic fibrosis patients short-term fluticasone therapy had no evident effect on clinical and sputum parameters. Further investigations are necessary to evaluate whether the observed up-regulation of oxidative capacity of inflammatory cells is of concern or benefit in these patients.

Administration, Inhalation↗
PubMed1999

Reverse transcription-competitive multiplex PCR improves quantification of mRNA in clinical samples--application to the low abundance CFTR mRNA.

BACKGROUND: To monitor gene therapy, we wished to quantify cystic fibrosis transmembrane conductance regulator (CFTR) mRNA. We developed a PCR-based method to measure CFTR mRNA in clinical samples. METHODS: Expression was determined by reverse transcription-competitive multiplex PCR (RCMP) for CFTR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts, and for serial dilutions of two internal cDNA standards consisting of CFTR and GAPDH mutants containing short deletions. The RCMP used simultaneous amplification of the gene of interest with a reporter gene in one reaction tube. The expression of CFTR was calculated with reference to the amount of GAPDH to correct for variations in initial RNA loading. RESULTS: Amplification of cDNAs derived from different amounts of RNA (1-4 microgram) gave similar GAPDH/CFTR ratios, with a coefficient of variation (CV) below 7.5%. RCMP was applied on nasal and bronchial brushings and shows a high variability of CFTR expression in non-cystic fibrosis donors. CONCLUSION: This method is precise and reproducible and advantageous for use with limited amounts of tissue, such as from biopsies or from nasal or bronchial brushings.

Bronchi↗
PubMed1999

[Gastrointestinal complications of adult patients with cystic fibrosis].

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. The primary cellular defect, the reduced expression of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to a chloride secretory defect, is present in all epithelial cells of endodermal and mesodermal origin and has been described in sweat glands, the airway epithelium and the small intestine, the colon and rectum, including the pancreas. In the upper GI-tract the most troublesome complaints and symptoms originating from the esophagus are peptic esophagitis or esophageal varices. In the small intestinal wall, the clinical expression of CF largely depends on the decreased secretion of fluid and chloride ions and the sticky mucous covering the enterocytes. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, distal intestinal obstruction (DIOS), and intussusception. In recent years an increase in colonic strictures after the use of high-dose pancreatic enzymes, has been increasingly reported. CF has also been reported to be increasingly associated with a number of hepatic and/or biliary abnormalities, of which chronic cholestatic liver disease is by far the most relevant. Plugging of intrahepatic bile ducts with inspissated secretions is thought to play a major role in the pathogenesis. It has been estimated that about 15% of cystic fibrosis patients reveal serum liver enzyme abnormalities, but prevalence of liver involvement is likely to be higher. Oral bile acid therapy is promising, but its long-term benefits in terms of survival and prevention of major complications by liver cirrhosis remain to be established. Pancreatic dysfunction in cystic fibrosis (CF) is characterized by an insufficient pancreatic exocrine function. However, 10-15% of CF patients have pancreatic sufficiency and this status is genetically determined by one or two "mild" mutations in the CFTR.

Adult↗
PubMed1998

Modulation of cystic fibrosis transmembrane conductance regulator gene - expression by elevation of intracellular cyclic AMP.

Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Its product is a cyclic AMP-dependent Cl- channel, that is defective in CF. Since cAMP regulates the expression of many genes and since the 5'-flanking region of the CFTR gene contains cAMP response elements, we hypothesized that intracellular cAMP might modulate not only the cAMP-dependent Cl- channel CFTR, but also CFTR gene expression in epithelial cells. To accomplish this, we investigated Cl- secretion and CFTR-mRNA levels in HT-29 and T84 colon carcinoma epithelial cells before and after exposure to forskolin and 8-bromo-cAMP for 12 hr. While resting T84 cells increased Cl- secretion in response to forskolin strongly and immediately, HT-29 cells did not, although both cell lines showed highly increased Cl- efflux in response to A23187, a calcium ionophore. Interestingly, prolonged exposure to forskolin (12 hr) induced a clear decrease of CFTR-mRNA levels in T84 cells, but an increase of CFTR-mRNA levels in HT-29 cells, thus demonstrating different behaviour of CFTR gene regulation in different epithelial cells in response to intracellular cAMP. These results suggest that cells with an effective cAMP-dependent Cl- channel (CFTR) respond to prolonged stimulation of this channel with down-regulation of CFTR gene expression, while cells with no effective cAMP-dependent Cl--secretion respond with an up-regulation of CFTR gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Investigating catalytic processes with parahydrogen: evolution of zero-quantum coherence in AA'X spin systems

A systematic outline for the elucidation of the nature of hydrogenation intermediates with a lifetime too short to be directly detectable with standard NMR methods is presented. The method takes advantage of the special nature of the parahydrogen density operator and its inherent enhancement factor. The key aspect of these experiments is the evolution of zero-quantum coherence which is contained in the parahydrogen density operator. Analytical coherence transfer functions have been derived which describe the evolution of this zero-quantum coherence in spin systems consisting of three spins 1/2 that form an AA'X spin system. The analytical expressions presented form a basis for a thorough investigation of crucial catalytic steps. Copyright 1998 Academic Press.

Journal Article↗
PubMed1997

Short-term effects of regular salmeterol treatment on adult cystic fibrosis patients.

Cystic fibrosis (CF) is characterized by chronic lung inflammation leading to airways obstruction. Bronchodilators, particularly short-acting beta2-agonists, are, therefore, often used by CF patients. The aim of this study was to evaluate, prospectively, the effects of the long-acting beta2-agonist salmeterol in adult CF patients. Twenty six patients with CF (10 males and 16 females; mean age (+/-SEM) 28+/-2 yrs) with mild-to-moderate airways obstruction (baseline forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 56+/-2%) were monitored in an open, cross-over trial for 4 weeks by means of peak expiratory flow rates (PEFR), self-recorded symptom scores and body plethysmography. During a 2 week run-in period, all patients continued their treatment, including regular short-acting beta2-agonists. In weeks 3 and 4, short-acting beta2-agonists were replaced by the long-acting beta2-agonist, salmeterol (50 microg b.i.d.). Salmeterol produced a significant increase in PEFR compared to the run-in period (morning 375+/-23 vs 332+/-23 L x min(-1), deltaPEFR +15.1+/-3.1%, p<0.003; evening 384+/-24 vs 349+/-24 L x min(-1), deltaPEFR +11.7+/-2.4%, p<0.04). Similarly, patients reported lower symptom scores, e.g. less dyspnoea during the day, fewer nocturnal awakenings, less intense cough, and fewer unscheduled puffs of short-acting beta2-agonists. Thus, the long-acting beta2-agonist salmeterol provided clinical benefit to a majority of adult cystic fibrosis patients with airways obstruction. These short-term results are promising enough to set up long-term controlled studies.

Administration, Inhalation↗