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Biomedical subjects

S S Pedersen

Publications and source records attributed to S S Pedersen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Correlation between specific IgG subclass antibodies to Pseudomonas aeruginosa and opsonic activity in serum from patients with cystic fibrosis.

Heat-stable opsonins from sera of patients with cystic fibrosis (CF) non-CF patients with chronic Pseudomonas aeruginosa infection, healthy children, and adults were investigated for their ability to promote phagocytosis of 35S-labeled P. aeruginosa by human polymorphonuclear neutrophils. Healthy children had significantly lower levels of opsonic activity than adults. Sera from patients with CF without chronic P. aeruginosa lung infection showed significantly higher levels of opsonic activity compared to healthy children. Sera from patients with CF in the early stage of chronic infection had similar opsonic activity as non-CF patients with chronic infection. Sera from patients with CF in the late stage of chronic infection had higher opsonic activity than other infected patients, but not different from adult controls. An inverse correlation was found between levels of specific antibodies to P. aeruginosa and opsonic activity in the group of patients in a late stage of infection. An inverse correlation was also found between levels of IgG1 and IgG3 to P. aeruginosa St-Ag and opsonic activity during the late stage of infection. Infection with P. aeruginosa in CF did not induce significantly increased opsonic activity. It seems that antibodies to P. aeruginosa may have inhibitory opsonic activity.

Adult↗
PubMed1994

Methodologic problems in establishing normal values for IgG subclass concentrations in a pediatric population; comparison of radial immunodiffusion and ELISA methods.

The aim of this study was to establish an enzyme-linked immunosorbent assay (ELISA) to measure IgG subclasses by means of monoclonal antibodies. The distribution of IgG subclass protein concentrations in sera from 227 healthy Danish children and 90 adults was measured. Furthermore, this newly established ELISA was compared with different assay systems for determination of IgG subclasses: two radial immunodiffusion methods (RID), one using polyclonal and one using monoclonal antibodies, as well as a commercially available ELISA kit. There was good agreement of results obtained by the different methods of measuring IgG3 and IgG4 concentrations. There was good correlation between results obtained by both RID methods. Despite good correlation between the assays, the ELISA kit showed higher levels of IgG1 in all investigated sera, and the ELISA kit showed no correlation with the other methods, when IgG2 was measured. Analysis of the normal ranges measured by ELISA developed in our laboratory and by RID with polyclonal antibodies showed that the levels obtained by RID were higher than those obtained by our ELISA in sera with low levels of both IgG1 and IgG2, and lower in sera with high concentrations of these two immunoglobulins. Our results emphasize the importance of establishing age-related normal limits for any novel assay measuring IgG subclass concentrations.

Adolescent↗
PubMed1994

Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center.

At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a beta-lactam antibiotic. We investigated the development of antibiotic resistance in P. aeruginosa strains isolated from Danish CF patients over a period of 18 years by testing the in vitro efficacy of carbenicillin, piperacillin, ceftazidime, tobramycin and ciprofloxacin against P. aeruginosa strains collected in 1973 (51 strains), 1980 (80 strains), 1985 (58 strains), and 1991 (100 strains). All the strains were screened and assayed semiquantitatively for beta-lactamase activity by use of nitrocefin. We found a significant (p < 0.005) increase in the MIC values of the P. aeruginosa strains against piperacillin and ceftazidime. However, no significant correlation was found between the MIC and the number of antipseudomonal courses of antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal beta-lactamase, also increased significantly during the period studied. Our results confirm that the beta-lactamase production is an important mechanism of antibiotic resistance in P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1993

[Plasmapheresis as life-saving treatment in acute hepatic failure].

Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure.

Acute Disease↗
PubMed1993

Effect of Pseudomonas aeruginosa alginate on Escherichia coli- and Staphylococcus aureus-induced inflammatory mediator release from human cells.

We analyzed the role of soluble purified Pseudomonas aeruginosa alginate on Escherichia coli K-12 (pANN5211) as well as on Staphylococcus aureus 121c-induced inflammatory mediator release from human platelets, granulocytes, and basophils. In the presence of alginate (1-4 mg/ml), the mucoid exopolysaccharide of P. aeruginosa, the bacteria-induced inflammatory mediator release was modulated as follows: (1) the E. coli- as well as S. aureus-induced chemiluminescence response from human neutrophils increased 2- to 3-fold and 5- to 6-fold, respectively; (2) the E. coli-induced leukotriene B4 formation from human neutrophils was enhanced (from 29.17 +/- 1.8 up to 36.9 +/- 4 ng/10(7) cells) as was also observed for the E. coli- and S. aureus-induced histamine release (3- to 4-fold) and the 12-hydroxyeicosatetraenoic acid generation from human platelets (2-fold), and (3) prolonged duration of the E. coli-induced increase in CD11b expression was observed. Alginate by itself was inactive. Our results provide evidence that alginate interacts with hemolysin-producing E. coli and S. aureus bacteria and thus leads to a modulation of the cellular response pattern, which leads to the local destruction of the lung in cystic fibrosis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Fluoroquinolones in the treatment of cystic fibrosis.

Cystic fibrosis patients suffer from recurrent and chronic lung infections mainly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The fluoroquinolones, notably ciprofloxacin and ofloxacin, represent an important addition to the therapy of P. aeruginosa infections. They offer the possibility of effective oral treatment for early colonisation as well as chronic infections, even in children. They are associated with only few and mild adverse effects. Development of resistance represents an increasing problem.

Ciprofloxacin↗
PubMed1993

Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats.

We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable to the lesions seen in cystic fibrosis (CF) patients. Early transitory IgM titers were demonstrated in both normal and athymic rats. Whilst athymic rats produced much lower IgG titers than the normal rats, presumably due to the absence of CD4+ cells, higher primary IgA titers were achieved. These two models in normal and athymic rats of the chronic lung infection resembling that seen in CF lungs make it possible to study the influence of the various components of the specific and nonspecific defense systems on the course of the chronic P. aeruginosa lung infection and to evaluate the effect of various immunization schedules and immunomodulatory drugs.

Acute Disease↗
PubMed1992

IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection.

Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.

Alginates↗
PubMed1992

Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis.

BACKGROUND: Chronic bronchopulmonary infection with mucoid, alginate producing Pseudomonas aeruginosa occurs characteristically in patients with cystic fibrosis. Alginate may be a virulence factor for P aeruginosa infection in such patients. METHODS: Forced vital capacity (FVC), nutritional state and the antibody response to P aeruginosa were determined at regular intervals from three years before chronic P aeruginosa infection to 10 years afterwards in 73 patients with cystic fibrosis. All patients were treated intensively with antipseudomonal chemotherapy during the study period. RESULTS: FVC was reduced in all patients who subsequently developed P aeruginosa infection before they acquired the infection, indicating significant pre-existing lung damage when compared with patients who remained free of P aeruginosa. Lung function and nutritional state remained unchanged after 10 years of infection, except in the patients who died of P aeruginosa lung infection. The FVC and height and weight of patients infected with nonmucoid strains of P aeruginosa were similar to those of uninfected patients. Patients infected with mucoid strains had poorer lung function and nutritional state for the first five years after infection compared with patients with nonmucoid strains. Such infection was also associated with greater IgG and IgA antibody responses to P aeruginosa standard antigen compared with nonmucoid infection. Concentrations of antibody to alginate were similar in patients with non-mucoid and mucoid infection. Noticeably increased concentrations of IgA antibodies to P aeruginosa standard antigen were observed early after the onset of infection in patients who subsequently died. CONCLUSION: Alginate producing P aeruginosa infection is associated with a hyperimmune response and poor clinical condition, suggesting that alginate production is a virulence factor in such infections in patients with cystic fibrosis.

Adolescent↗
PubMed1992

Alginate--its role in neutrophil responses and signal transduction towards mucoid Pseudomonas aeruginosa bacteria.

Mucoid Pseudomonas aeruginosa bacteria impaired neutrophil functions, e.g. chemiluminescence response, and leukotriene formation to a significantly higher degree as compared to nonmucoid P. aeruginosa bacteria. To study the cell biological requirements for the different cellular response pattern by mucoid and nonmucoid (NM) P. aeruginosa bacteria, further experiments were performed with purified alginate, the mucoid exopolysaccharide of P. aeruginosa (MEP). In this regard the MEP (alginate) significantly reduced the zymosan-induced leukotriene B4 (LTB4) formation (from 40 +/- 7 to 2 +/- 4 ng). The chemiluminescence response induced by NM bacteria was abolished when the bacteria were precoated with the MEP. Mucoid and NM P. aeruginosa bacteria interacted with components of the cellular signal transduction pathway to a different degree. Mucoid bacteria induced a 2-fold enhanced GTPase activity but activated the protein kinase C (PKC) to a lesser degree than NM P. aeruginosa bacteria. Prior exposure of neutrophils to the MEP increased the sodium fluoride (NaF)-induced GTPase activity and guanylylimidodiphosphate binding [Gpp(NH)p] by approximately 60 and 30%, respectively. The phorbol myristic acid-induced PKC activation was inhibited by 30-40% in the presence of the MEP. However, the MEP by itself was inactive in all assay systems. Our results indicate that the MEP represents an important component which modulates neutrophil responses of mucoid as compared to NM P. aeruginosa bacteria, e.g. the chemiluminescence response, LTB4 generation, and the interaction with components (G proteins, PKC) of the signal transduction pathway.

Alginates↗
PubMed1992

Immunoglobulin allotypes and IgG subclass antibody response to Pseudomonas aeruginosa antigens in chronically infected cystic fibrosis patients.

Chronic Pseudomonas aeruginosa lung infection is the leading cause of death in patients with cystic fibrosis (CF). Poor prognosis correlates with a high number of anti-pseudomonas precipitins and with high levels of IgG2 and IgG3 anti-pseudomonas antibodies. Reports of several highly significant associations between certain Gm (genetic markers of IgG on human chromosome 14) and Km (k-type light chain determinants on chromosome 2) phenotypes and immune responsiveness to various antigens suggest that allotype-linked immune response genes do exist in man. Furthermore correlation between Gm types and IgG subclass levels has been reported. A group of 143 CF patients were investigated (31 non-infected and 112 chronic infected). The IgG subclass antibodies to three different P. aeruginosa antigens (P. aeruginosa standard antigen (St-Ag), alginate and LPS) were determined. Immunoglobulin allotypes were determined by haemagglutination inhibition. Samples were typed for G1m(1,2,3, and 17), G2m(23), G3m(5,21), and Km(1,3). Statistical analysis of our data demonstrate that IgG3 anti-pseudomonas antibody levels and Gm markers are related. IgG3 antibody levels to all investigated P. aeruginosa antigens are significantly higher in sera homozygous for Gm(3;5), somewhat lower in heterozygous sera, and significantly lower in sera homozygous for Gm(1,2,17;21). We suggest that genetic differences between the patients may explain the present differences in subclass patterns.

Antibodies, Bacterial↗
PubMed1992

Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis.

Progressive pulmonary insufficiency is the major cause of morbidity and mortality in patients with the inherited disease cystic fibrosis. The basic defect involves a disturbed ion transport across cells, but it is not known how this leads to the airways becoming highly susceptible to recurrent respiratory tract infection with S. aureus, H. influenzae and P. aeruginosa as the dominating pathogens. P. aeruginosa is not a primary pathogen in CF and some degree of lung damage generally has taken place before colonization begins at approximately 10 years of age. Cross-infection occurs and the incidence of P. aeruginosa infection can be reduced by interrupting person-to-person spread. P. aeruginosa infection is a chronic infection that is never permanently eradicated. However, intensive antipseudomonal chemotherapy has contributed to improved survival rates. 90% of patients remain alive more than 10 years after onset of chronic P. aeruginosa and, on an average, they can maintain an almost unchanged lung function during that period. Diagnosis of chronic infection rests on bacteriological examination and demonstration of a specific antibody response. Immunological assays to detect an early antibody response were developed. It is characteristic, but not specific for CF, that chronic lung infection is caused by alginate producing mucoid P. aeruginosa. Alginate biosynthesis is under complex genetic control and possibly regulated by environmental factors. Alginate was purified from mucoid P. aeruginosa and characterized and it was shown to be immunologically heterogenous. It is generally assumed that the infection begins with strains that are nonmucoid, but serological analysis show that these strains probably also produce the mucoid substance, alginate, in vivo. Patients infected with mucoid strains demonstrate a significantly higher antibody response to all P. aeruginosa antigens and have a lower lung function when compared to patients infected with nonmucoid strains. Despite the pronounced humoral antibody response efficient immune clearance of P. aeruginosa does not occur. Mucoid P. aeruginosa are organisms that are deficient in most of the classical virulence factors. In vivo it grows in a protected biofilm as mucoid microcolonies, where bacteria are enmeshed in a loosely bound, highly hydrated extracellular matrix of alginate. Purified alginate was shown to inhibit chemotaxis of neutrophil leukocytes and unable to activate complement. A deficient SIgA antibody response to alginate has been observed in bronchial secretions and it was hypothesized to be associated with the epithelial transport defect.(ABSTRACT TRUNCATED AT 400 WORDS)

Alginates↗
PubMed1992

Mucosal immunity to Pseudomonas aeruginosa alginate in cystic fibrosis.

Patients with cystic fibrosis commonly acquire chronic pulmonary infection with alginate-producing Pseudomonas aeruginosa. The infection remains localized at the mucosal surfaces of the airways. Using enzyme-linked immunosorbent assays immunoglobulin concentrations and titers of specific antibodies to purified P. aeruginosa alginate and to P. aeruginosa sonicated antigens were measured in tears, saliva, sputum and serum. CF patients had significantly higher concentrations of IgG, IgA and SIgA in serum and saliva than controls. They also had significantly higher levels of specific antibodies to alginate and sonicated antigen in secretions and serum. Local production of IgA, IgG and IgM antibodies to P. aeruginosa was demonstrated. Only a minor proportion of specific IgA antibodies were present as secretory IgA in tears, saliva and sputum. The ratio of alginate-specific SIgA to specific monomeric IgA in sputum was significantly lower than the similar ratio in saliva, whereas the same ratio for specific P. aeruginosa sonicate antigens was found in saliva and sputum.

Adolescent↗
PubMed1991

Serum antibodies to Pseudomonas aeruginosa outer-membrane proteins and iron-regulated membrane proteins at different stages of chronic cystic fibrosis lung infection.

Serum samples collected over periods up to 15 years from nine patients with cystic fibrosis (CF) were investigated by immunoblotting and crossed immuno-electrophoresis (CIE) for antibodies to Pseudomonas aeruginosa outer-membrane proteins (OMPs). The earliest antibody response to OMPs was directed against proteins G, H1 and I. Detection by immunoblotting sometimes preceded the CIE response; the appearance of antibodies to the other major OMPs was co-incident with an increase in CIE precipitins. Isolation of the mucoid form of P. aeruginosa was associated with a rapid increase in both precipitin numbers and antibodies detected by immunoblotting. Antibodies to iron-regulated OMPs could be detected in all the serum samples that showed eight or more CIE precipitins but their presence became pronounced only in the advanced stages of disease. The clinical strain used in this study and other isolates from CF patients showed several atypical OMPs, perhaps as a consequence of antibiotic therapy or related to the serum sensitivity of mucoid P. aeruginosa. Their expression in vivo was confirmed by detecting antibodies to them in patients' serum.

Antibodies, Bacterial↗
PubMed1991

Experimental immunization with Pseudomonas aeruginosa alginate induces IgA and IgG antibody responses.

We tried experimentally to induce a specific antibody response against Pseudomonas aeruginosa locally in the airways and systemically in rats by three different routes of immunization; intragastric feeding, intratracheal inoculation or subcutaneous vaccination. Three groups of rats were immunized with live mucoid P. aeruginosa PAO 579 by intragastric feeding or with killed PAO 579 intratracheally or subcutaneously. Three other groups were immunized with purified P. aeruginosa alginate either by intragastric feeding, intratracheally or subcutaneously. At weekly intervals for four weeks animals were sacrificed and serum and bronchial fluid were obtained. The specific IgA and IgG antibody response in lavage fluid and serum was measured. Only traces of antibodies could be detected in the bronchial lavage fluids. Anti-alginate IgA and IgG antibodies developed in all rats immunized with alginate but no antibodies against other P. aeruginosa antigens were detected. The highest IgA and IgG titer against alginate was induced by the subcutaneous immunization. IgA and IgG antibodies against other P. aeruginosa antigens developed in rats immunized with liver and sonicated bacteria. The highest IgA and IgG titers were obtained after intratracheal and subcutaneous immunization with sonicated bacteria. The present work has shown that IgA and IgG antibodies develop with high specificity after immunization. The different titers obtained do not necessarily reflect different degrees of protection.

Alginates↗
PubMed1990

Peroral treatment with ciprofloxacin of patients with spinal cord lesion and bacteriuria caused by multiply resistant bacteria.

Eleven patients, median age 38 years, with spinal cord lesion (SCL) and urinary tract infection (UTI) caused by multiply resistant bacteria entered an open clinical trial of peroral ciprofloxacin 250 mg b.i.d. for 6 days. P. aeruginosa was the most prevalent bacteria. Ciprofloxacin was clinically effective in all patients who had symptoms of UTI at entry. Bacterial eradication was achieved in 9 out of 11 patients immediately after treatment. At 4 weeks post-treatment 5 patients had relapse of bacteriuria with the initial micro-organism and only 2 had long term eradication. One patient had transient elevation of transaminases, but no other adverse reactions were noted. Pharmacokinetic analysis showed that ciprofloxacin was readily absorbed with a terminal half life of 2.5 hours and considerable nonrenal elimination. The urinary concentration of ciprofloxacin was high during the whole dosing interval. Oral treatment with ciprofloxacin is an alternative to parenteral antibiotics in SCL-patients with urinary tract infection caused by resistant bacteria.

Adult↗