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Biomedical subjects

G Döring

Publications and source records attributed to G Döring.

At least 91 records · Page 5Linked to original sources
PubMed1989

Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis.

Activation of human neutrophils (PMN) is accompanied by rapid upregulation of CR1, the C3b receptor, and CR3, the iC3b receptor, which also serves as the PMN's major adherence protein. This is necessary for migration and phagocytosis, but the extent of expression of these proteins on PMN at inflammatory sites has not been determined. We used monoclonal antibodies and flow cytometry to assess CR1 and CR3 expression on PMN in bronchoalveolar lavage (BAL) fluid of cystic fibrosis (CF) patients chronically infected with pseudomonas and in sterile joint fluid of arthritis patients. Resting peripheral blood PMN from these patients and normals expressed similar low levels of CR1 and CR3, and the patients' PMN increased CR1 and CR3 expression normally when stimulated in vitro. CR3 expression on CF BAL PMN was 90 +/- 12% of that on the same patient's blood cells stimulated in vitro with FMLP. In contrast, CR1 expression on BAL PMN was only 27 +/- 8% of that on stimulated blood cells. Similar results were obtained for joint PMN. This pattern could be reproduced in vitro by treating FMLP-stimulated blood cells with BAL supernatants or with pseudomonas or PMN elastase. The serine protease inhibitors, PMSF and alpha 1-antitrypsin prevented the lavage supernatant from reducing CR1 expression, while metalloprotease inhibitors had no effect. Treatment of PMN with elastase in vitro decrease their ability to kill opsonized Pseudomonas aeruginosa. These results suggest that PMN at inflammatory sites have maximally upregulated expression of their complement receptors, but that CR1 is then cleaved by proteolysis in situ. Although not related to the basic defect in CF, this may interfere with efficient phagocytosis and contribute to the CF patient's inability to eradicate chronic lung infection.

Adult↗
PubMed1989

[The significance of bacterial and host factors in corneal infections caused by Pseudomonas aeruginosa].

Two pathogenic mechanisms are discussed as possibly being responsible for destruction of the corneal tissue in the course and corneal infections caused by Pseudomonas aeruginosa. One involves bacterial exoenzymes and the other polymorphonuclear (PNM)-derived lysosomal enzymes. The objective of the present study was (1) to show the relative importance of the two mechanisms and (2) to evaluate the effect of active immunization against Pseudomonas aeruginosa exoenzymes on ocular damage. Rabbits were immunized against Pseudomonas aeruginosa alkaline protease (AP) or elastase (Ela) and challenged with the respective enzymes. Corneal damage was studied by light photography. In another group rabbits were immunized against AP, Ela and exotoxine A and challenged with Pseudomonas aeruginosa strain PA 01 und PA 103. Corneal damage was studied by light photography, light microscopy and electron microscopy. Immunized animals were totally protected against purified Pseudomonas aeruginosa exoenzymes. Less corneal damage was found in immunized rabbits than in non-immunized ones. 12 and 24 h after infection with whole bacteria. However, after 48 h corneal damage was comparable in both groups. These results show that corneal damage by lysosomal enzymes from stimulated PMN ist more important in Pseudomonas aeruginosa than direct damage by bacterial exoenzymes.

ADP Ribose Transferases↗
PubMed1989

Molecular epidemiology of Pseudomonas aeruginosa--urinary tract infections in paraplegic patients.

84 Pseudomonas aeruginosa strains from 29 paraplegic patients with urinary tract infections (UTI) and from the water reservoirs of specialized wards in two German hospitals were typed using a P. aeruginosa-specific DNA probe. P. aeruginosa strains were present in 51% of all accessible water reservoirs, including sinks of wash-basins and toilets in the wards. 14 of the 29 patients with UTI (48%) were infected by P. aeruginosa strains which were also isolated from these sources. Groups of up to four patients were infected by single strains. Some of the strains persisted in the wards and were isolated from the water reservoirs five to eight months after causing UTI. 89.5% of the investigated water samples yielded P. aeruginosa strains which were identical with strains from up to nine other sites. The wide distribution of single P. aeruginosa genotypes in the ward, the isolation of strains causing UTI from rooms inaccessible to the patients, and the outbreak of UTI caused by single, identical P. aeruginosa strains in groups of patients within short time periods, suggest that the strains are distributed by the personnel rather than by the patients who for the most part are immobile.

Cross Infection↗
PubMed1989

Effect of Pseudomonas aeruginosa rhamnolipid on human neutrophil and monocyte function.

The effect of rhamnolipid purified from culture supernatant of Pseudomonas aeruginosa on human peripheral blood neutrophil and monocyte function was studied. It was shown that rhamnolipid at concentrations of up to 100 micrograms/ml did not affect neutrophil and monocyte chemotaxis towards various chemoattractants. The rhamnolipid by itself did not show chemotactic activity and did not induce any oxidative burst response. Preincubation of monocytes with rhamnolipid enhanced the oxidative burst response of these cells to phorbol myristate acetate (PMA) and to opsonized zymosan by 2 to 5 fold. The priming effect was observed both in a superoxide assay and in a chemiluminescence assay. However, rhamnolipid did not prime the neutrophil oxidative burst response. Monocytes/macrophages are involved in the inflammatory process in the lung infections caused by P. aeruginosa and oxygen radicals are known to cause tissue damage. Therefore the priming by rhamnolipid of monocytes for enhanced generation of oxygen radicals may play a role in the pathogenesis of tissue damage in the lungs of cystic fibrosis patients with P. aeruginosa infections.

Glycolipids↗
PubMed1988

Impact of proteases on iron uptake of Pseudomonas aeruginosa pyoverdin from transferrin and lactoferrin.

The Pseudomonas aeruginosa siderophore pyoverdin was unable to acquire iron from human transferrin or lactoferrin at physiological pH. However, in the presence of P. aeruginosa elastase, rapid iron release and pyoverdin iron uptake from transferrin but not from lactoferrin were detected. Neither P. aeruginosa alkaline protease nor elastase from polymorphonuclear leukocytes revealed this effect.

Carrier Proteins↗
PubMed1988

Staphylococcus aureus capsular types and antibody response to lung infection in patients with cystic fibrosis.

Chronic respiratory tract infections caused by Staphylococcus aureus are common in patients with cystic fibrosis (CF). Recently, it was shown in a few CF patients that S. aureus isolates produce capsular polysaccharides (CPs). However, it is not known whether this is a common feature and whether an immune response to CPs in CF is detectable. Therefore, we examined 170 S. aureus isolates from CF patients and healthy individuals for production of CP types 5 and 8 by using monoclonal antibodies. We found that CP-producing staphylococcal isolates were randomly distributed among CF patients and healthy carriers. Eighty-five percent of all isolates produced CPs, 77% of which were type 8. Examination of one sputum sample by an immunofluorescence technique suggested that production of CPs is not an in vitro phenomenon. S. aureus isolates from various sites of a single person often yielded more than one CP type. A random distribution of S. aureus strains with CP type 5 or 8 from the skin and respiratory tracts of patients and from the skin of healthy individuals was found. Antibody response to CP types 5 and 8, measured by enzyme-linked immunosorbent assay, was not elevated in CF patients with chronic S. aureus lung infection in comparison with healthy carriers. On the contrary, in CF patients the ratios of antibodies to CP 8 were significantly lower (P less than 0.005; alpha = 0.025). The ratios of antibodies to CP types did not change when monitored longitudinally over several months. This study suggests that the production of CPs is a universal property of S. aureus and that infected CF patients do not have elevated ratios of antibodies to these antigens.

Antibodies, Bacterial↗
PubMed1988

Clearance of Pseudomonas aeruginosa in different rat lung models.

Chronic pulmonary infections with Pseudomonas aeruginosa remain a serious problem in patients with cystic fibrosis. Structurally altered lung mucosa and local inflammation may impair bacterial clearance from the airways. This hypothesis was investigated in (1) the reserpinized rat, (2) proteinase-pretreated rat lungs, and (3) Type III hypersensitivity rat lung models. Reserpine treatment led to surface alterations of Type I epithelial lung cells and diminished food uptake. Significantly enhanced P. aeruginosa colony-forming units (CFU) were found in all (12 of 12) rat lungs 48 h after challenge compared to partially starved rats (p less than 0.025) or untreated rats (p less than 10(-6)). Pretreatment of normal rat lungs with elastase from polymorphonuclear leukocytes (PMN-elastase) resulted in extensive tissue damage, and 48 h after bacterial challenge the mean P. aeruginosa CFU of 12 animals was significantly higher 1.1 X 10(4) +/- 1.0 X 10(4) CFU; p less than 0.01) than in the reserpinized rat lungs. P. aeruginosa organisms were also found in PMN-elastase-treated rat lungs not challenged with bacteria (five of 12 animals), suggesting cross infection from infected animals in the same cage. In immunized rats that were challenged with aerosolized antigen (bovine serum albumin) and P. aeruginosa, bacterial CFU after 10 h were significantly higher than in nonimmune animals (p less than 0.005), and highest after 48 h when P. aeruginosa alkaline proteinase was used as the antigen (1.2 X 10(5) +/- 1.4 X 10(5) CFU). These data provide new evidence that clearance of P. aeruginosa from lung tissue is impaired after malnutrition, epithelial cell alteration, or epithelial cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Immunologic aspects of cystic fibrosis.

Bacterial infections determine life expectancy in the hereditary disease cystic fibrosis (CF). The dominant pathogens are Staphylococcus aureus and Pseudomonas aeruginosa, which persist in the patient's respiratory tract. Current explanations of the chronicity of the infections in the apparently immunocompetent host are based on defective opsonophagocytosis. This may be caused by (1) bacterial exopolysaccharide production, leading to cryptic infection types; (2) cleavage of immunoglobulin, complement, and surface receptors on immunocompetent cells by host proteases; and (3) a change from opsonic to nonopsonic antibody isotypes. Continuous antigenic stimulation of the immune system leads to local immune complex formation and a high chronic hypersensitivity reaction as well as to temporary immune unresponsiveness. Progressive tissue damage caused by lysosomal enzymes and oxygen radicals from polymorphonuclear leukocytes is thought to be ultimately responsible for respiratory failure and death in CF. Besides antibiotic treatment, anti-inflammatory therapy is therefore currently considered beneficial.

Antibodies, Bacterial↗
PubMed1988

Iron-chelating substances and inflammation.

The effect of Pseudomonas aeruginosa alkaline protease (AP), elastase (Ela), and the elastase from polymorphonuclear leukocytes (PMN Ela) on iron acquisition of pyoverdin from human transferrin and lactoferrin at physiologic pH was investigated. Incubation of iron-loaded transferrin with iron-free pyoverdin for 10 h at 40 degrees C in the presence of Ela yielded pyoverdin-iron(III) complex, in contrast to incubations of transferrin with pyoverdin alone, AP, or PMN Ela. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the incubations revealed fragmentation of transferrin by Ela in peptides smaller than 14,000 daltons, whereas AP and PMN Ela cleaved transferrin in fragments of 49,000 d and 43,000 d, respectively. Incubations of lactoferrin with the proteases and pyoverdin or pyoverdin alone did not result in iron acquisition by pyoverdin; however, lactoferrin was fragmented by Ela and AP.

Bacterial Proteins↗
PubMed1988

Demographic study on the family planning behaviour of the German population: the importance of natural methods.

A total of 1,267 women in the F.R.G., aged from 15 to 45 years, were interviewed about their family planning behavior and the importance of natural methods of family planning (NFP) in a representative demographic study. It was found that 19.6% of the respondents were not sexually active. The others used various methods, as follows: pill, 38.4%; IUD, 10.3%; condom, 5.9%; diaphragm, 2.1%; spermicides, 0.8%; withdrawal, 3.4%; NFP methods, 3.9%. The main reason for rejecting a method was a possible medical risk. Of the responding women, 73% had some previous knowledge about NFP; 47% of them found such methods to be interesting, and approximately 20% indicated a high probability of the use of NFP methods in the future.

Adolescent↗
PubMed1987

[Significance of Pseudomonas aeruginosa virulence factors for acute and chronic Pseudomonas aeruginosa infections].

The virulence of Pseudomonas aeruginosa is multifactorial and caused by several extracellular enzymes and other substances. The importance of these virulence factors for the pathogenesis of human P. aeruginosa infections is dependent on the type of infection. For acute, systemic infections in immunocompromised patients, exotoxin A, alkaline protease and elastase are essential virulence factors. In localized infections (e. g., cystic fibrosis) they seem to be of minor importance, since they are neutralized by specific antibodies in immune complexes, and in the case of exotoxin A cleavage by proteinases from polymorphonuclear leukocytes occurs. The rhamnolipid of P. aeruginosa which has been detected in sputa of patients with cystic fibrosis evades the host's immune response and has to be regarded as a potential virulence factor together with the phenazine pigments, also in chronic P. aeruginosa infections.

ADP Ribose Transferases↗
PubMed1987

Prognostic implications of circulating immune complexes and Pseudomonas aeruginosa-specific antibodies in cystic fibrosis.

We re-examined the role of circulating immune complexes (CIC) in cystic fibrosis, by their serial measurement in 16 patients who had advanced lung disease and persistent specific antibodies to Pseudomonas aeruginosa in their serum. CIC were detected by 125I C1q-BA (IgG + IgM-IC) and Raji RIA (IgG-IC), and IgA-IC by a modification of the Raji RIA method. Serum precipitins to Ps. aeruginosa were detected by crossed-immunoelectrophoresis (XIE) and antibodies to alkaline protease (AP), elastase (EL) and exotoxin-A (EA) of Ps. aeruginosa were detected by ELISA technique. CIC were positive in greater than 50% of the samples in 8 patients (group A) and in less than 25% in the other 8 (group B); follow-up averaged 22 mo in group A and 26 mo in group B. The numbers of precipitins to Pseudomonas were equally high, and levels of antibodies to AP, EL, and EA of Ps. aeruginosa were similarly positive, in the 2 groups. In group A the CIC were mostly IgG-IC by Raji RIA (76%) and IgA-IC, whereas in group B C1q-binding IC (79%) and IgA-IC were more prevalent than IgG-IC by Raji RIA. Four group A children died during follow-up, together with one group B child in whom the CIC level had suddenly risen precipitously. We postulate that a high level of CIC in association with persistent specific-antibody response to Ps. aeruginosa heralds a poor prognosis in cystic fibrosis.

Adolescent↗