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Biomedical subjects

L Hagberg

Publications and source records attributed to L Hagberg.

126 records · Page 7Linked to original sources
PubMed1983

Ascending, unobstructed urinary tract infection in mice caused by pyelonephritogenic Escherichia coli of human origin.

A model for ascending unobstructed urinary tract infection was developed in mice to study the pathogenesis of urinary tract infection induced by Escherichia coli associated with urinary tract infection in humans. Specifically, the model was designed to monitor the initial stages of the infectious process, e.g., bacterial adhesion. Mice were selected since the specificity and intensity of bacterial attachment of pyelonephritogenic E. coli strains to human and mouse uroepithelial cells were similar. Female mice were infected by urethral catheterization and installation of bacteria in the urinary bladder. To maximize clearance of unattached bacteria, no obstructive manipulations were performed. After sacrifice, the persistence of bacteria in kidneys and bladder was determined by viable counts on homogenized tissues. The experimental infection was standardized by using one pyelonephritis (HU734) and one normal fecal (414) E. coli isolate. With both strains all of the bladders became infected, but E. coli 414 was eliminated more rapidly than HU734. The percentage of positive kidney cultures increased with the bacterial inoculum concentration and volume. An inoculum of 0.05 ml containing 10(10) bacteria per ml was selected, giving the highest percentage of positive kidney cultures without detectable bacterial spread to the blood stream. The variation in the percentage of positive kidney cultures possibly depended on the degree of vesicoureteric reflux in the individual animals. Both in the kidneys and in the urinary bladders, strain HU734 yielded higher numbers of bacteria at 24 h and persisted longer than did strain 414. Several E. coli pyelonephritis isolates with properties associated with virulence in the human urinary tract consistently were recovered from mouse kidneys and bladders in higher numbers than E. coli strains of human fecal origin lacking those properties. The role of bacterial adhesion per se is the topic of the accompanying paper.

Adhesiveness↗
PubMed1982

Inhibition of experimental ascending urinary tract infection by an epithelial cell-surface receptor analogue.

It has been shown that the establishment of urinary tract infection by Escherichia coli is dependent on attachment of the bacteria to epithelial cells. The attachment involves specific epithelial cell receptors, which have been characterized as glycolipids. Reversible binding to cell-surface mannosides may also be important. This suggests an approach to the treatment of infections--that of blocking bacterial attachment with cell membrane receptor analogues. Using E. coli mutants lacking one or other of the two binding specificities (glycolipid and mannose), we show here that glycolipid analogues can block in vitro adhesion and in vivo urinary tract infection.

Animals↗
PubMed1982

Chemical and clinical studies on the interaction of Escherichia coli with host glycolipid receptors in urinary tract infection.

The role of glycosphingolipids as host receptors, and fimbriae as bacterial ligands, for the adhesive and hemagglutinating reactions of uropathogenic E. coli was assessed. Glycolipids including globotetraosylceramide and globotriaosylceramide, which contain the disaccharide Gal alpha 1 leads to 4Gal were bound by many strains isolated from patients with pyelonephritis and cystitis. The fimbriae of one strain were shown to serve as ligands for these receptors. Although most pyelonephritic E. coli recognized globotetraosylceramide, as measured by the agglutination of glycolipid coated erythrocytes, some also recognized D-mannose residues (i.e. mannose-sensitive hemagglutination). Several strains were exclusively mannose-sensitive or bound neither globotetraosylceramide nor mannose. A genetic basis for susceptibility to infection was indicated. The erythrocytes of blood group P2 have lower amounts of Gal alpha 1 leads to 4Gal containing glycolipids than individuals of blood group P1. Blood group P2 was significantly less frequent (1/28) among patients with recurrent urinary tract infection compared to the normal population (10/40, p less than 0.02). Therefore, globoseries glycolipids may be determinants of susceptibility to urinary tract infection.

Binding Sites↗
PubMed1981

Adhesion of Escherichia coli in urinary tract infection.

In individuals prone to urinary tract infections the intestine is colonized by E. Coli strains that possess a combination of properties determining virulence. Such an E. coli strain may colonize the vaginal and periurethral area and ascend the urinary tract. The ability to attach to the mucosal surface is thought to be essential for E. coli to colonize and to remain in the urinary tract. Most E. coli from patients with urinary tract infection show one or both of two adherence properties. One may depend on the recognition by type 1 fimbriae of mannose-containing residues in the urinary slime. It is measured as mannose-sensitive haemagglutination and is found on most E. coli strains. The second adherence property is detected as attachment to human urinary tract epithelial cells and as mannose-resistant agglutination of human erythrocytes. This may depend on the recognition of globo-series glycolipids in the epithelial cell surface. Possession of this adherence factor is strongly related to virulence. Most strains from patients with acute pyelonephritis and cystitis have this property but it is rare in strains from patients with asymptomatic bacteriuria and strains from normal faeces. Local antibodies may interfere with bacterial attachment, thus possibly preventing the colonization that precedes urinary tract infection or modifying an established infection. Vaginal antibodies are known to coat E. coli from the stools. Antibodies in the urine of patients with acute pyelonephritis inhibit attachment of the infecting strain to uroepithelial cells. Antibodies directed against several bacterial surface structures, for example O antigen and fimbriae, are likely to inhibit attachment by steric hindrance or agglutination. The role of antibodies in adhesion-mediating structure such as fimbriae in susceptibility to and the outcome of human urinary tract infection remains to be investigated.

Adhesiveness↗
PubMed1981

Adhesion, hemagglutination, and virulence of Escherichia coli causing urinary tract infections.

The capacity of 453 Escherichia coli strains to agglutinate erythrocytes and yeast cells and to attach to human urinary tract epithelial cells was tested. The strains were isolated from the urine of patients with acute pyelonephritis, acute cystitis, or asymptomatic bacteriuria and from the stools of healthy school children. Three main patterns of hemagglutination were found: (i) mannose-resistant agglutination of human erythrocytes alone or simultaneously with mannose-sensitive agglutination of guinea pig erythrocytes; (ii) only mannose-sensitive agglutination of guinea pig and other erythrocytes; and (iii) no agglutination. Strains with mannose-resistant agglutination of human erythrocytes alone or in combination with mannose-sensitive hemagglutination attached in high numbers to human urinary tract epithelial cells. Bacteria inducing only mannose-sensitive hemagglutination attached in low numbers, and non-agglutinating strains did not bind to the urinary tract epithelial cells. The bacterial surface antigen(s) mediating mannose-resistant hemagglutination of human erythrocytes and attachment to human urinary tract epithelial cells may be one factor selecting for E. coli from among the fecal flora which infect the urinary tract. The highest proportion of strains with this property was found among acute pyelonephritis isolates (77%), and the lowest proportion of strains with this property was found among normal fecal E. coli (16%).

Agglutination↗
PubMed1980

Elevated serum levels of pancreatic secretory proteins in cigarette smokers after secretin stimulation.

The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.

Adult↗
PubMed1980

Collagen synthesis in granulation tissue formed in rats treated with female sex hormones.

In previous studies, we have shown that female sex hormones given in dosages corresponding to plasma levels in the last trimester of pregnancy retard collagen accumulation in early phases of experimental granulation tissue formation. Results of incorporation experiments using radioactive proline reported in this article indicate that this hormone treatment reduces general protein synthesis in granulation tissue and, even more markedly, the synthesis of collagen. Since collagen accumulation into granulomas is normal in the later phases of healing, it is suggested that hormone treatment not only decreases synthesis of collagen but also decreases breakdown of collagen. Hormone treatment did not affect the solubility of labeled collagen. No differences were observed in the synthesis of different collagen types. Under conditions when active collagen and protein synthesis occurs in the uterus and fetus, corresponding synthesis in other tissues is, thus, decreased. This may serve as an energy and protein saving function during pregnancy. The results may have applications for treatment of extensive scar formation.

Animals↗
PubMed1978

The healing process of transplanted digital tendon sheath synovium. Experimental autoradiographic studies in chickens.

The present investigation is a sequel to a previous report on the composition and fate of the pseudo-sheath formed by secondary healing, and of free tendon sheath autografts covering defects in the digital tendon sheaths of chickens (Eiken & Rank, 1977). Autoradiography was used to determine graft survival and cell regeneration. The distribution of labelled cells indicated that the granulation tissue of secondary healed defects formed around implanted Silastic rods consists of fibrous scar tissue. The tendon sheath autografts, on the other hand, were found to survive, demonstrating a well-preserved synovial surface. These findings probably imply new concepts of tendon surgery. The Silastic rod induced some foreign body reaction in the healing synovium. It is assumed that this reaction is reversible, but this could not be established in the present investigation. Further study is being made of this problem.

Animals↗
PubMedDate not supplied

Recent progress in the understanding of the role of bacterial adhesion in the pathogenesis of urinary tract infection.

There is extensive evidence indicating that the capacity of Escherichia coli to attach to the mucosal lining of the urinary tract is a virulence factor in acute pyelonephritis in the unobstructed state. In vitro results using human uroepithelial cells and clinical E. coli isolates as well as in vivo work on ascending urinary tract infection in mice and E. coli strains with genetically defined adhesins support this notion. The biochemical characterization of the bacterial ligands and epithelial cell receptors important for the attachment of most pyelonephritogenic E. coli provides a more sophisticated means of evaluating the role of bacterial adhesion in urinary tract infection: 1) It allows precise diagnosis of the receptor specificity of clinical isolates; 2) The receptor can be used to isolate the relevant bacterial adhesins; 3) The localization and quantity of the receptor in the patient may be of prognostic importance; 4) The administration of soluble receptor analogues or antibodies to the adhesins may be useful for prophylactic and/or therapeutic purposes.

Adhesins, Escherichia coli↗
PubMedDate not supplied

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearence from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗
PubMedDate not supplied

Non-antibiotic prevention of urinary tract infection.

The identification of several glycoconjugates as receptors for attaching bacteria has resulted in optimism regarding the use of receptor analogues in preventing infection. The structure of receptor-active oligosaccharides and the patient groups which might benefit from such treatment are most thoroughly understood for urinary tract infections. Prevention of adhesion and delay or decrease of infection was achieved using oligosaccharides from the globoseries of glycolipids containing Gal alpha 1----4Gal. This minimal receptor structure as a free saccharide was, however, not sufficient. It was the intact P, P1 and pk determinants which showed optimal activity in vitro. In addition, protection against experimental UTI results from previous exposure to whole bacteria or isolated antigens. The mechanism(s) of protection and their relevance in clinical UTI remain to be defined.

Animals↗
PubMedDate not supplied

Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis.

Elevated (greater than 3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis.

Adolescent↗
PubMedDate not supplied

Cerebrospinal fluid neopterin and beta 2-microglobulin levels in neurologically asymptomatic HIV-infected patients before and after initiation of zidovudine treatment.

The effect of zidovudine on beta 2-microglobulin and neopterin in the cerebrospinal fluid (CSF) was studied in ten HIV-seropositive neurologically healthy individuals. CSF concentrations of neopterin decreased by 53% (from 20.3 to 9.5 nmol/l, p < 0.01) and beta 2-microglobulin by 36% (from 2.8 to 1.8 mg/l, p < 0.01) four to eight months after initiation of therapy.

Biopterins↗
PubMedDate not supplied

Increased cerebrospinal fluid levels of glial fibrillary acidic protein (GFAp) in Lyme neuroborreliosis.

Glial fibrillary acidic protein (GFAp), the main protein constituent of the intermediate filaments of astrocytes, was analysed in the cerebrospinal fluid (CSF) of 20 patients with Lyme neuroborreliosis as a marker of the astroglial reaction. The mean GFAp level before antibiotic treatment in the study group was significantly elevated (592 pg/ml +/- 596 [SD]) compared to that in 24 healthy controls (121 +/- 87 [SD]) (p < 0.01). The highest CSF-GFAp levels were seen in the patients with the most severe disease, but the levels were also increased in patients with peripheral paresis, such as facial palsy with no or only minor encephalitic symptoms. This implies that the infection was not limited to radix dorsalis or the meningeal tissues, but affected the central nervous system as well. Furthermore, the astroglial reaction seemed to occur early in Lyme neuroborreliosis since CSF-GFAp levels were elevated also in patients with recent (< 3 weeks) onset of disease. After antibiotic treatment, the GFAp levels decreased. It is suggested the CSF-GFAp concentrations might be useful for monitoring CNS involvement in Lyme neuroborreliosis.

Adolescent↗