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Biomedical subjects

C Svanborg-Edén

Publications and source records attributed to C Svanborg-Edén.

At least 19 recordsLinked to original sources

Endotoxin levels in sera of elderly individuals.

The endotoxin levels in serum of 377 72-year-old individuals were quantitated. The study population was a representative sample of this age group and was participating in a general study of health and disease among the elderly in Göteborg, Sweden. The endotoxin levels in serum were quantified by the chromogenic Limulus amebocyte lysate assay and were correlated with the health status and laboratory findings for each individual. The mean endotoxin levels (+/- 1 standard deviation) in men and women, when excluding four outliers, were 6.6 +/- 3.8 and 6.9 +/- 3.8 pg/ml, respectively. All included, 21.5% of individuals had endotoxin levels equal to or above the sensitivity limit of 10 pg/ml. Strong positive correlations were found between endotoxin levels and plasma triglycerides (P > 0.995) and between endotoxin levels and serum protein (P > 0.9875). The endotoxin activity also correlated with mean corpuscular hemoglobin concentration (P < 0.005, negative correlation), body mass index (P > 0.9875), and decreased appetite (P > 0.9875). A high alcohol consumption was associated with increased endotoxin levels (P = 0.995). There are no previous studies which examine endotoxin levels in serum samples from individuals representative of the population. This study showed that elderly individuals had the same mean level of endotoxin as has been found in other age groups. The increased endotoxin levels seen in heavy drinkers may be explained by a decreased ability of the liver to remove endotoxin. The correlations found between endotoxin and triglycerides, protein, mean corpuscular hemoglobin concentration, decreased appetite, and body mass index are discussed.

Aged↗

Follicular cystitis in girls with untreated asymptomatic or covert bacteriuria.

Nodular changes of the bladder mucosa, that is cystitis follicularis or cystitis cystica, are found in 2 to 9% of all children with urinary tract infections. The nodules are composed of lymphoid aggregates, resembling Peyer's patches in the intestine. Children with this finding are considered to have a poor short-term prognosis with a marked tendency for recurrent infections. Screening programs for bacteriuria have revealed that a few per cent of the female population are bacteriuric without symptoms of overt disease. Of 59 girls followed with untreated asymptomatic bacteriuria 52 had nodular changes of the bladder mucosa at cystoscopy. Biopsy was performed in 22 girls, and revealed lymphocytic infiltration in 19 and follicular formation in 11. The nodular changes persisted when bacteriuria continued but disappeared in patients who became abacteriuric. This finding demonstrates the reversibility of the changes, and supports the assumption that they are secondary to the presence of bacteria and not a primary lesion.

Bacteriuria↗

Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria.

Gram-negative bacterial infections of the urinary tract elicit a mucosal inflammatory response. Interleukin-6 is secreted into the urine, and polymorphonuclear leukocytes (PMNL) are recruited. In the present study we examined the effect of anti-inflammatory agents on these parameters and on bacterial clearance from the kidneys. Dexamethasone reduced interleukin-6 secretion, the PMNL response, and bacterial clearance. Diclofenac abolished the urinary interleukin-6 response but reduced the PMNL response and bacterial clearance only at the highest concentrations. Indomethacin drastically decreased bacterial clearance without the corresponding effect on interleukin-6 production or the PMNL response. The results demonstrate that the inhibition of inflammation impairs bacterial clearance from the kidneys. This is, however, not a direct function of inhibited interleukin-6 production or PMNL recruitment.

Animals↗

Glycosphingolipid receptors for Pseudomonas aeruginosa.

The binding of Pseudomonas aeruginosa to glycosphingolipids and to buccal and bronchial epithelial cells was analyzed. Three independently expressed specificities were found by bacterial binding to glycosphingolipids separated by thin-layer chromatography. All strains bound gangliotria- and gangliotetrasylceramide. All but one of the strains bound sialic acid-containing glycosphingolipids and lactosylceramide. The latter two specificities could be separated in that the lactosylceramide binding was retained and the sialic acid binding was suppressed when bovine serum albumin was used as a blocking agent in the thin-layer chromatography assay. The attachment to buccal epithelial cells, like the binding to sialylated compounds and lactosylceramide, was abolished by Formalin treatment of the bacteria, suggesting the importance of these specificities for cell adherence. In contrast, the binding to gangliotria- and gangliotetraosylceramide was retained by nonattaching Formalin-treated bacteria.

Antigens, CD↗

Untreated asymptomatic bacteriuria in girls: I--Stability of urinary isolates.

OBJECTIVE: To assess the frequency of spontaneous changes of bacterial strains in patients with untreated asymptomatic bacteriuria. DESIGN: Retrospective analysis of samples from all patients with renal scarring and random sample of patients with normal kidneys. SETTING: Outpatient clinic for children with urinary tract infections. PATIENTS: 54 Girls aged 3.3-15.5 years with untreated asymptomatic bacteriuria caused by Escherichia coli. INTERVENTION: None. END POINT: Change in bacterial strain. MEASUREMENTS AND RESULTS: Serotyping and electrophoretic analysis of sequential bacterial isolates, representing 151 patient years of untreated asymptomatic bacteriuria. A total of 24 changes of strain were identified. Eleven were related to medical interference such as treatment of other infections with antibiotics. CONCLUSIONS: Spontaneous changes of strain were uncommon, one change in 11.6 patient years, and thus are not a characteristic feature of the course of asymptomatic bacteriuria.

Adolescent↗

Untreated asymptomatic bacteriuria in girls: II--Effect of phenoxymethylpenicillin and erythromycin given for intercurrent infections.

OBJECTIVE: To investigate the effects of phenoxymethylpenicillin and erythromycin on urinary isolates from patients with untreated asymptomatic bacteriuria. DESIGN: Retrospective study of subgroup of patients from cohort followed up till the end of 1986. SETTING: Outpatient clinic for children with urinary tract infections. PATIENTS: 51 Girls aged under 15 with untreated asymptomatic bacteriuria. INTERVENTIONS: Before 1982 intercurrent infections (mostly tonsillitis or otitis) were treated with phenoxymethylpenicillin; after 1982 erythromycin treatment was preferred. END POINTS: Change of bacterial strain in urinary tract and symptomatic recurrences of disease. MEASUREMENTS AND MAIN RESULTS: Bacteria identified by serotype and electrophoretic type and compared before and after antibiotic treatment. Bacteriuria eradicated and replaced by new strains in most patients treated with phenoxymethylpenicillin, leading to symptomatic recurrences in about 15%. Conversely, patients given erythromycin rarely showed change in bacteriuria and none suffered symptomatic recurrence. CONCLUSIONS: In girls with untreated asymptomatic bacteriuria the use of phenoxymethylpenicillin for intercurrent infections may lead to a change of urinary bacteria and leave them at substantial risk of acute pyelonephritis. With erythromycin this risk is small (2/20 courses in this series).

Adolescent↗

Bacteriuria in pregnancy. Frequency and risk of acquisition.

A total of 3,254 pregnant women attending two antenatal clinics in Göteborg, Sweden, were screened for bacteriuria. The coverage of the pregnant population in the areas served by the two clinics was estimated to be 88%. Of the women who were registered at the two clinics, 99% took part in at least one screening; 71% were screened during each of the three intervals. The high frequency of screening of the women made it possible to estimate the risk of acquiring bacteriuria during pregnancy. This risk increased with the duration of pregnancy from 0.8% of bacteriuric women in the 12th gestational week to 1.93% at the end of pregnancy. The risk of onset of bacteriuria was highest between the ninth and 17th gestational weeks. The 16th gestational week was the optimal time for a single screening for bacteriuria calculated as the number of bacteriuria-free gestational weeks gained by treatment.

Adult↗

Molecular analysis and epidemiology of the Dr hemagglutinin of uropathogenic Escherichia coli.

The genetic organization and epidemiology of Dr hemagglutinin was studied. Plasmids derived from pBJN406 and carrying transposon inserts were analyzed for their abilities to confer the mannose-resistant hemagglutination phenotype and expression of plasmid-encoded proteins. The 6.6-kilobase DNA fragment expressed five polypeptides with molecular masses of 15.5, 5, 18, 90, and 32 kilodaltons encoded by the draA, draB, draC, draD, and draE genes, respectively. Four genes, draA, draC, draD, and draE, were required for full mannose-resistant hemagglutination expression. Mutation in the draA gene, previously identified as encoding fimbrillin, resulted in loss of the adherence phenotype. We screened 658 strains isolated from patients with urinary tract infections (UTI) or from fecal samples for the presence of DNA sequences homologous to the draD gene. A significantly higher frequency of draD-related sequences was found among Escherichia coli strains from patients with cystitis than among strains from patients with other clinical forms of UTI. Association of draD-related sequences with O75 and other serotypes was observed. A possible role of Dr hemagglutinin as a virulence factor in lower UTI is discussed.

Bacterial Proteins↗

Distribution of the P-associated-pilus (pap) region among Escherichia coli from natural sources: evidence for horizontal gene transfer.

Variation in chromosomal DNA in Escherichia coli was studied with probes specific for the P-associated-pilus (pap) region. The presence of DNA homologous to pap was determined by dot blots. Variation in the number of copies of pap and in the organization of internal and flanking sequences was determined by Southern blot hybridization. The 229 strains studied were also classified by O:K:H serotyping and multilocus enzyme electrophoresis. There was considerable heterogeneity in the presence of pap and distribution of pap-homologous DNA in these E. coli strains from natural sources. In general, there was less variation in pap among strains of the same specific O:K:H serotype and enzyme electrophoretic type than among random isolates. There were, however, E. coli strains identified as members of the same clone by O:K:H serotyping and enzyme electrophoresis that were pap positive and pap negative or had different Southern blot patterns for the pap probes (pap type). There were also isolates of the same pap type that differed in two of three O:K:H serotype antigens and the majority of enzymes that determined their enzyme electrophoretic type. These latter two observations were interpreted as evidence for the horizontal (infectious) transfer of the pap-homologous sequences among clones of E. coli.

Bacterial Adhesion↗

Turnover of nontypable Haemophilus influenzae in the nasopharynges of healthy children.

The nasopharyngeal Haemophilus influenzae flora of healthy children in a day care center was analyzed by repeated sampling during 4 winter months. The average carrier rate was 39%, but 74% of the children became colonized at some time during the study. The H. influenzae isolates were identified by capsular type, biotype, and multilocus enzyme electrophoresis. The turnover of the flora in individual children and in the day-care group was characterized. Four patterns of colonization were defined among the 38 children and 49 H. influenzae strains. Depending on the persistence in the group, the strains were designated as endemic, i.e., shared between several children on several occasions, or as epidemic, i.e., occurring only once but in several children. The individual hosts had two patterns; resident strains persisted for 2 weeks or more, and transient strains showed no evidence of persistence. The results suggest that there is considerable sharing of certain nontypable H. influenzae among healthy children in day care, whereas other strains remain restricted to a single host. The properties of host and bacteria determining these patterns remain to be defined.

Child↗

Attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells.

Streptococcus pneumoniae and Haemophilus influenzae are major respiratory pathogens. They attach to the mucosal surfaces of the respiratory tract. This attachment is the first contact with the host tissues and may determine whether the bacteria will colonize the mucosa and cause infection. Conversely, if attachment is inhibited, the infection may be prevented. Our studies have defined the mechanisms of pneumococcal attachment as a specific interaction between bacterial proteins and epithelial cell glycoconjugates. The free oligosaccharide blocks adhesion. So does human milk, which contains the receptor oligosaccharides. The accessibility of receptors is likely to be influenced by secreted substances like mucins, surfactant, etc. The effect of such components has not been evaluated. Ambroxol, bromhexin, as well as secretions from individuals treated with the substances may have such activity.

Ambroxol↗

A sandwich adhesion on Streptococcus pneumoniae attaching to human oropharyngeal epithelial cells in vitro.

Streptococcus pneumoniae attach to human pharyngeal epithelial cells through the specific interaction of bacterial surface adhesins with glycoconjugate receptors. The present study defines the adhesin as a molecule bridging between an anchoring site in the bacterial cell wall and the epithelial cell receptor. The nature of the adhesin was defined in three ways: First, the attachment of whole bacteria was reduced by trypsin, periodate and heat. Second, heat treatment of whole bacteria was shown to release material, which was able to reconstitute the adherence. The heat extract bound to epithelial cells, as shown by fluorescence labelling, and agglutinated latex beads covalently coupled with receptor oligosaccharide. Active material could be extracted by heat from both high and low adhering strains, but could reconstitute only attaching strains. Third, the bacterial component binding the adhesin was localized to protoplasts and cell wall fractions obtained by mechanical or deoxycholate induced lysis of pneumococci. Isolated pneumococcal surface components, which did not inhibit attachment, included peptidoglycan, C polysaccharide, Forssmann antigen, capsular polysaccharide and a phenol extract produced in analogy to streptococcal lipoteichoic acid. The procedure used to extract the adhesin was previously used to prepare the competence factor. The competence deficient mutant RA7- attached poorly compared to the competent R6 parent. The possible relatedness of attachment to competence is discussed.

Adhesins, Bacterial↗

Induction of inflammation by Escherichia coli on the mucosal level: requirement for adherence and endotoxin.

Bacterial infection of the mouse urinary tract is followed by the recruitment of leukocytes to the mucosal surface. This study examined the bacterial components involved in the induction of this response. Escherichia coli of serotype O75:K5:H- expressing adhesins specific for the Gal alpha 1-4Gal beta- (Gal, galactose) and mannose-containing receptors were instilled into the urinary bladder of lipopolysaccharide responder (C3H/HcN) and lipopolysaccharide nonresponder (C3H/HeJ) mice. The inflammation was quantitated as the number of leukocytes excreted into the urine at various times after infection. The response was first shown to depend on the Lps genotype of the mouse. The leukocyte excretion that occurred within 24 h after infection of C3H/HeN mice was absent in C3H/HeJ mice. The components triggering the response were present on both live and Formalin-killed bacterial cells, and the response was mimicked by intravesical inoculation of isolated lipid A. Pretreatment of bacteria with soluble receptor oligosaccharides resulted in inhibition of attachment in vitro and of the inflammation in vivo. A direct synergy between adhesins specific for Gal alpha 1-4Gal beta receptors and lipid A was demonstrated. Mixtures of these components induced a leukocyte response higher than the sum of the responses to each component alone. These results suggest that the inflammation induced by gram-negative bacteria in the urinary tract can be triggered at the level of the epithelial cells by endotoxin presented by an attaching bacterial cell and that intact function at the Lps locus of the host is required for this to occur.

Animals↗

Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection.

The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.

Acute Disease↗

Host parasite interaction in urinary tract infection.

The last decade has provided new insight into the mechanisms of host-parasite interactions in the urinary tract. Reduction of host resistance appears to reduce the requirement for bacterial virulence, whereas the resistant host becomes infected with bacteria of high virulence. In the resistant host, bacterial virulence can be defined as the sum of properties required to colonize the urinary tract and induce tissue reactions. The ability to attach to uroepithelial cells is the single property most frequently associated with pyelonephritogenic clones. Attachment to the Gal alpha 1-4Gal beta-containing receptors promotes localization of bacteria to the kidney and the induction of lipopolysaccharide-mediated inflammation. Other virulence factors, defined by increased frequency in acute pyelonephritis compared with asymptomatic bacteriuria, include haemolysin and aerobactin production. Among the factors which influence the natural resistance to urinary tract infection are urinary flow and reactivity to endotoxin. The resistance induced by natural exposure to infection or immunization may be protective in experimental models, but the importance of this is not yet defined. The localization, severity and sequelae of urinary tract infection are determined by the balance between bacterial virulence and host resistance. Although disease is a result of the interaction between bacterial virulence and host resistance, these components are discussed separately for clarity.

Humans↗

Virulence factors of Escherichia coli in urinary isolates from pregnant women.

Urinary isolates from 24 pregnant women with acute pyelonephritis and from 37 pregnant women with bacteriuria detected at screening were characterized for O:K:H serotype, electrophoretic type, adherence, hemolysin production, and serum resistance. Between the two diagnostic groups, only three clones were identical. For the remaining isolates, both the identification markers and virulence traits differed significantly. The strains from pregnant women with pyelonephritis did not significantly differ from those from non-pregnant women. Thus, pregnancy was shown not to abolish the difference in virulence between Escherichia coli causing acute pyelonephritis and asymptomatic bacteriuria.

Acute Disease↗

Lack of correlation of in vitro adherence of Haemophilus influenzae to epithelial cells with frequent occurrence of otitis media.

The adherence to human epithelial cells, biotype and capsular type of 175 Haemophilus influenzae cultured from the upper respiratory tract were studied in a prospective study of children with recurrent otitis media. Forty-three children who had greater than 2 episodes of acute otitis media (AOM) during the first year of life were followed for at least 1 year. Cultures of the oropharynx were done periodically, and the middle ear fluid (MEF) was cultured at the time of AOM. H. influenzae was recovered from MEF in 44% of the 136 AOM episodes recorded. Thirty-one children had at least one episode of AOM caused by H. influenzae; the remaining 12 children, designated as "controls," had no otitis or had AOM caused by other organisms. The possible differences between carriage and infection strains were evaluated by comparison of MEF and oropharyngeal isolates, by pairwise comparison of MEF and oropharyngeal isolates and by pairwise comparison of multiple isolates from each host recovered at the time of AOM and during infection-free intervals. No significant differences in patterns of adherence, capsular type or biotype were found. The lack of correlation between these characteristics and infection suggests either that H. influenzae organisms have determinants of virulence yet to be defined or that variations in host susceptibility permit infection by the strain colonizing the upper respiratory tract. Adherence per se may be less important in the development of infection than in establishing and maintaining colonization within the host.

Acute Disease↗