| 1. |
- Baker, N, et al.
(författare)
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Glycosphingolipid receptors for Pseudomonas aeruginosa.
- 1990
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Ingår i: Infection and immunity. - 0019-9567. ; 58:7, s. 2361-6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Brisuda, Antonín, et al.
(författare)
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Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
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| 3. |
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| 4. |
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| 5. |
- Hedges, S., et al.
(författare)
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Uroepithelial cells are part of a mucosal cytokine network
- 1994
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Ingår i: Infection and Immunity. - 0019-9567. ; 62:6, s. 2315-2321
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Tidskriftsartikel (refereegranskat)abstract
- This study compared the cytokine production of uroepithelial cell lines in response to gram-negative bacteria and inflammatory cytokines. Human kidney (A498) and bladder (J82) epithelial cell lines were stimulated with either Escherichia coli Hu734, interleukin 1α (IL-1α), or tumor necrosis factor alpha (TNF-α). Supernatant samples were removed, and the RNA was extracted from cells at 0, 2, 6, and 24 h. The secreted cytokine levels were determined by bioassay or immunoassay; mRNA was examined by reverse transcription-PCR. The two cell lines secreted IL-6 and IL-8 constitutively. IL-6 and IL-8 mRNA were constitutively produced in both cell lines; IL-1β mRNA was detected in J82 cells. IL-1α induced significantly higher levels of IL-6 secretion than did E. coli Hu734 or TNF-α. IL-1α and TNF-α induced significantly higher levels of IL-8 secretion than did E. coli Hu734. Secreted IL-1β was not detected; IL-1α and TNF-α were not detected above the levels used for stimulation. IL-1α, IL-1β, IL-6, and IL-8 mRNAs were detected in both cell lines after exposure to the stimulants. TNF-α mRNA was occasionally detected in the J82 cell line after TNF-α stimulation. Cytokine (IL-6 and IL-8) and control (glyceraldehyde 3-phosphate dehydrogenase [G3PDH] and β-actin) mRNA concentrations were quantitated with internal PCR standards. Cytokine mRNA levels relative to β-actin mRNA levels were the highest in E. coli- stimulated cells. In comparison, the cytokine mRNA levels relative to G3PDH mRNA levels were the highest in IL-1α-stimulated cells. β-Actin mRNA levels decreased after bacterial stimulation but not after cytokine stimulation, while G3PDH mRNA levels increased in response to all of the stimulants tested. These results suggested that E. coli Hu734 lowered the β-actin mRNA levels in uroepithelial cells, thus distorting the IL-6 and IL-8 mRNA levels relative to this control. In summary, E. coli IL-1α and TNF-α were found to activate the de novo synthesis and secretion of IL-6 and IL-8 in uroepithelial cells. These results emphasize the role of epithelial cells in cytokine-mediated responses during the early stages of infection.
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| 6. |
- Hedman, E., et al.
(författare)
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Effectiveness of Internet-based cognitive behaviour therapy for depression in routine psychiatric care
- 2014
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 155:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efficacy of guided Internet-based cognitive behaviour therapy (ICBT) for depression has been demonstrated in several randomised controlled trials. Knowledge on the effectiveness of the treatment, i.e. how it works when delivered within routine care, is however scarce. The aim of this study was to investigate the effectiveness of ICBT for depression.Methods: We conducted a cohort study investigating all patients (N =1203) who had received guided ICBT for depression between 2007 and 2013 in a routine care setting at an outpatient psychiatric clinic providing Internet-based treatment The primary outcome measure was the Montgomery Asberg Depression Rating Scale-Self rated (MADRS-S).Results: Patients made large improvements from pre-treatment assessments to post-treatment on the primary outcome (effect size d on the MADRS-S = 1.27, 99% CI, 1.14-1.39). Participants were significantly improved in terms of suicidal ideation and sleep difficulties improvements were sustained at 6-month follow-up.Limitations: Attrition was rather large at 6-month follow-up. However, additional data was collected through telephone interviews with dropouts and advanced statistical models indicated that missing data did not bias the findings.Conclusions: ICBT for depression can be highly effective when delivered within the context of routine psychiatric care. This study suggests that the effect sizes are at least as high when the treatment is delivered in routine psychiatric care by qualified staff as when delivered in a controlled trial setting.
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| 7. |
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| 8. |
- Sheppard, Neil C, et al.
(författare)
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Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.
- 2014
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 26:10, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- Polyethyleneimine (PEI) is an organic polycation used extensively as a gene- and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits, and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration, and enhanced antigen uptake by antigen presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome, however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When co-formulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased towards a Th1-type immune profile. Taken together these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens.
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