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- Jackmann, Natalja, et al.
(author)
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The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases
- 2022
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In: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 198:6, s. 1023-1031
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Journal article (peer-reviewed)abstract
- The human cathelicidin hCAP-18 (pro-LL-37) is the pro-protein of the antimicrobial peptide LL-37. hCAP-18 can be produced by many different cell types; bone marrow neutrophil precursors are the main source of hCAP-18 in the circulation. Neutrophil count is used as a marker for myelopoiesis but does not always reflect neutrophil production in the bone marrow, and thus additional markers are needed. In this study, we established the reference interval of serum hCAP-18 level in healthy children and compared serum hCAP-18 levels between different diagnostic groups of children with haemato-oncological diseases, at diagnosis. We found that children with diseases that impair myelopoiesis, such as acute leukaemia, aplastic anaemia, or myelodysplastic syndrome, presented with low hCAP-18 levels, whereas patients with non-haematological malignancies displayed serum hCAP-18 levels in the same range as healthy children. Children with chronic myeloid leukaemia presented with high circulating levels of hCAP-18, probably reflecting the high number of all differentiation stages of myeloid cells. We suggest that analysis of serum hCAP-18 provides additional information regarding myelopoiesis in children with haemato-oncological diseases, which may have future implications in assessment of myelopoiesis in clinical management.
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- Pütsep, Katrin
(author)
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On the control of the microflora in the gastro intestinal tract : functional examples of antibacterial peptides from Helicobacter pylori and mouse small intestine
- 2000
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Doctoral thesis (other academic/artistic)abstract
- The human microflora contains at least 400 different species mainly localized to the gastro-intestinal tract. This indigenous flora is controlled by host factors as well as by the interference within the microbial community through the action of antimicrobial components. These components are in the focus of this thesis. A microprotocol was developed for biochemical analysis of antimicrobial peptides in tiny tissue material. The protocol was based on a one extraction step, followed by separation on HPLC and mass-spectrometry analysis. This method was sensitive enough for the detection of antimicrobial substances of the small intestine from a single mouse. Ribosomal proteins with antibacterial activity contributed substantially to the microbicidal activity, in addition to already known components such as defensins, lysozyme and phospholipase A. Using this protocol we could demonstrate that the processing of prodefensins to mature microbicidal defensin peptides involves at least two-steps. No major impact of the microflora on the production of antimicrobial components in the small intestine could be found except for the production of the peptide CRS4-4C. We found that the gastro-intestinal bacteria Helicobacter pylori possessed antibacterial activity. The origin of this activity was traced to cecropin like N-terminal fragments of ribosomal protein L1 (RpL1). Synthetic peptides based on the H. pylori N-terminal sequence were antibacterial but lacked cytolytic as well as hemolytic properties. To H. pylori this antibacterial activity may confer survival advantage during the colonisation phase of a new host when the pH is raised and H. pylori may have to face other faster growing bacteria. The antibacterial activity from ribosomal proteins was found to be a common theme for both the mouse small intestine and H. pylori. The impact of microbicidal substances on host microbe interactions is an important factor for the understanding of the dynamics of the normal microflora. By the use of the microprotocol described here it may become possible to biochemically analyse these substances from human biopsies.
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- Sofrata, Abier, et al.
(author)
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Benzyl Isothiocyanate, a Major Component from the Roots of Salvadora Persica Is Highly Active against Gram-Negative Bacteria
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23045-
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Journal article (peer-reviewed)abstract
- Plants produce a number of antimicrobial substances and the roots of the shrub Salvadora persica have been demonstrated to possess antimicrobial activity. Sticks from the roots of S. persica, Miswak sticks, have been used for centuries as a traditional method of cleaning teeth. Diverging reports on the chemical nature and antimicrobial repertoire of the chewing sticks from S. persica led us to explore its antibacterial properties against a panel of pathogenic or commensal bacteria and to identify the antibacterial component/s by methodical chemical characterization. S. persica root essential oil was prepared by steam distillation and solid-phase microextraction was used to sample volatiles released from fresh root. The active compound was identified by gas chromatography-mass spectrometry and antibacterial assays. The antibacterial compound was isolated using medium-pressure liquid chromatography. Transmission electron microscopy was used to visualize the effect on bacterial cells. The main antibacterial component of both S. persica root extracts and volatiles was benzyl isothiocyanate. Root extracts as well as commercial synthetic benzyl isothiocyanate exhibited rapid and strong bactericidal effect against oral pathogens involved in periodontal disease as well as against other Gram-negative bacteria, while Gram-positive bacteria mainly displayed growth inhibition or remained unaffected. The short exposure needed to obtain bactericidal effect implies that the chewing sticks and the essential oil may have a specific role in treatment of periodontal disease in reducing Gram-negative periodontal pathogens. Our results indicate the need for further investigation into the mechanism of the specific killing of Gram-negative bacteria by S. persica root stick extracts and its active component benzyl isothiocyanate.
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- Sundin, Mikael, et al.
(author)
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Novel STAT3 Mutation Causing Hyper-IgE Syndrome : Studies of the Clinical Course and Immunopathology
- 2014
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 34:4, s. 469-477
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Journal article (peer-reviewed)abstract
- Purpose Reporting a clinical case with a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene resulting in autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). Here we also had the opportunity to perform in-depth immunologic investigations to further understand the immunopathology of this primary immunodeficiency. Methods The patient, a baby boy, was clinically assessed according to the scoring system developed by Grimbacher et al. and STAT3 was investigated by DNA sequencing. Immunologic work-up consisted of lymphocyte phenotyping and proliferation assays, measurement of soluble mediators and routine investigations. Results According to the Grimbacher score the patient was likely to have AD-HIES and a novel heterozygous STAT3 mutation (c.1110-3C>A), causing a splice error, was identified. Lymphocyte phenotyping revealed decreased numbers of interleukin (IL)-17 producing T-helper lymphocytes and aberrant B-lymphocyte subsets. Proliferative in vitro lymphocyte responses against C. albicans, staphylococcal enterotoxins and pokeweed mitogen were supernormal at presentation, whereas only the elevated response to pokeweed mitogen persisted. The soluble mediators IL-5, -10, -12, -13, -15 and granulocyte colony stimulatory factor were elevated in serum. Conclusion A novel heterozygous STAT3 mutation causing defective splicing of exon 12 was identified. Lymphocyte phenotyping revealed deranged subpopulations. Despite the clinical picture with severe C. albicans and staphylococcal infections, the patient’s lymphocytes mounted responses to these pathogens. The hypereosinophilia and high immunoglobulin E levels might partly be explained by elevated IL-5 and -13 as a result of lack of negative feedback from defective STAT3 signaling.
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