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- Ciornei, Cristina, et al.
(författare)
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Bactericidal/permeability-increasing protein inhibits endotoxin-induced vascular nitric oxide synthesis.
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:9, s. 1111-1118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. METHODS: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5-48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1beta (IL-1beta); (c) BPI; (d) BPI + LPS; (e) BPI + IL-1beta or (f) neither BPI, LPS nor IL-1beta (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells. RESULTS: Both LPS and IL-1beta decreased contractility and increased NO production, as well as iNOS. Co-incubation with BPI attenuated all the effects of LPS but only the effects of prolonged exposure to IL-1beta in cultured cells. CONCLUSION: We conclude that BPI attenuates the LPS-induced changes in vascular reactivity by inhibiting the expression of iNOS resulting in decreased NO formation and restored responsiveness to vasoconstrictors. The data suggest that BPI can prevent circulatory disturbances during Gram-negative sepsis.
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| 4. |
- Ciornei, Cristina, et al.
(författare)
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Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study
- 2006
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 6:49
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Death of smooth muscle cells in the atherosclerotic plaques makes the plaques more prone to rupture, which can initiate an acute ischemic event. The development of atherosclerosis includes the migration of immune cells e.g. monocytes/macrophages and T lymphocytes into the lesions. Immune cells can release antimicrobial peptides. One of these, human cathelicidin antimicrobial peptide hCAP-18, is cleaved by proteinase 3 generating a 4.5 kDa C-terminal fragment named LL-37, which has been shown to be cytotoxic. The aim of the study was to explore a potential role of LL-37 in the pathophysiology of atherosclerosis. METHODS: We investigated the presence of LL-37 in human atherosclerotic lesions obtained at autopsy using immunohistochemistry. The direct effects of LL-37 on cultured vascular smooth muscle cells and isolated neutrophil granulocytes were investigated with morphological, biochemical and flow cytometry analysis. RESULTS: The neointima of atherosclerotic plaques was found to contain LL-37-like immunoreactivity, mainly in macrophages. In cultured smooth muscle cells, LL-37 at 30 mug/ml caused cell shrinkage, membrane blebbing, nuclear condensation, DNA fragmentation and an increase in caspase-3 activity as studied by microscopy, ELISA and enzyme activity assay, respectively. Flow cytometry demonstrated that LL-37 in a subset of the cells caused a small but rapidly developing increase in membrane permeability to propidium iodide, followed by a gradual development of FITC-annexin V binding. Another cell population stained heavily with both propidium iodide and FITC-annexin V. Neutrophil granulocytes were resistant to these effects of LL-37. CONCLUSION: This study shows that LL-37 is present in atherosclerotic lesions and that it induces death of vascular smooth muscle cells. In a subset of cells, the changes indicate the development of apoptosis triggered by an initial mild perturbation of plasma membrane integrity. The findings suggest a role for LL-37 as a mediator of immune cell-induced death of vascular smooth muscle cells in atherosclerosis.
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| 5. |
- Ciornei, Cristina
(författare)
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Vascular actions of antimicrobial peptides
- 2006
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 50:5, s. 631-631
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Ciornei, Cristina
(författare)
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Vascular actions of antimicrobial peptides
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis focuses on the vascular effects of antimicrobial peptides especially mechanisms involving the vasodilator nitric oxide (NO), which is released from the blood vessel wall during inflammatory conditions such as sepsis. Bacterial lipopolysaccharide stimulates the expression of nitric oxide synthase (iNOS), which increases the NO production in vascular tissues or cultured vascular smooth muscle cells (VSMC). We found that bactericidal/permeability-increasing protein (BPI) attenuated the lipopolysaccharide-induced increase in NO production in rat aorta and cultured smooth muscle cells in vitro via suppression of lipopolysaccharide-induced expression of iNOS. The effects of the human endogenous antimicrobial peptide LL-37 on lipopolysaccharide -induced iNOS expression and NO production were studied on rat aortas and rat VSMC. LL-37 reduced the lipopolysaccharide-induced iNOS expression and nitric oxide production but after a longer exposure time it was also found to be cytotoxic. The morphological and biochemical changes induced by LL-37 in cultured rat aortic VSMC were thus further investigated and we found that LL-37 induces programmed cell death (apoptosis), indicating that the use of native LL-37 as a therapeutic agent may be limited. We therefore evaluated the effects of some LL-37 analogs, regarding antimicrobial activity, lipopolysaccharide neutralization and toxicity against human erytrocytes and human VSMC. As truncated analogs of LL-37 were similar to LL-37 concerning antimicrobial and lipopolysaccharide neutralization while being less cytotoxic than LL-37, we conclude that they are potential candidates in the treatment of sepsis.
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| 7. |
- Ericson Lindquist, Kajsa, et al.
(författare)
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Difficulties in diagnostics of lung tumours in biopsies : an interpathologist concordance study evaluating the international diagnostic guidelines
- 2022
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Ingår i: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 75:5, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Accurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria.METHODS: Fifty-two unselected lung and bronchial biopsies were diagnosed by a thoracic pathologist based on a broad spectrum of immunohistochemical (IHC) stainings, molecular data and clinical/radiological information. Slides stained with H&E, thyroid transcription factor-1 (TTF-1) clone SPT24 and p40 were scanned and provided digitally to 20 pathologists unaware of reference diagnoses. The pathologists independently diagnosed the cases and stated if further diagnostic markers were deemed necessary.RESULTS: In 31 (60%) of the cases, ≥80% of the pathologists agreed with each other and with the reference diagnosis. Lower agreement was seen in non-small cell neuroendocrine tumours and in squamous cell carcinoma with diffuse TTF-1 positivity. Agreement with the reference diagnosis ranged from 26 to 45 (50%-87%) for the individual pathologists. The pathologists requested additional IHC staining in 15-44 (29%-85%) of the 52 cases. In nearly half (17 of 36) of the malignant cases, one or more pathologist advocated for a different final diagnosis than the reference without need of additional IHC markers, potentially leading to different clinical treatment.CONCLUSIONS: Interpathologist diagnostic agreement is moderate for small unselected bronchial and lung biopsies based on a minimal panel of markers. Neuroendocrine morphology is sometimes missed and TTF-1 clone SPT24 should be interpreted with caution. Our results suggest an intensified education need for thoracic pathologists and a more generous use of diagnostic IHC markers.
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| 9. |
- Johansson, Karin, et al.
(författare)
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Axillary Web Syndrome : Evidence for Lymphatic Origin with Thrombosis
- 2020
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Ingår i: Lymphatic Research and Biology. - : Mary Ann Liebert Inc. - 1539-6851 .- 1557-8585. ; 18:4, s. 329-332
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Tidskriftsartikel (refereegranskat)abstract
- Background: The axillary web syndrome (AWS) occurs in the axilla and on the frontal side of the upper arm and sometimes along the forearm to the thumb. The cord is painful, particularly on movement, and can therefore be very distressing for the patient. Although the phenomenon has been examined and discussed for decades, no evidence for the origin has been found until now. The aim of this study was to perform a histopathologic analysis of cords taken between 1996 and 1998 in the Surgical Clinic, Skane University Hospital, Lund, Sweden. Methods and Results: In seven patients, biopsies of the AWS cords were obtained 4-5 weeks after axillary node surgery for breast cancer and examined with standard hematoxylin and eosin and D2-40 (lymphatic endothelial cell) staining. In one biopsy, there was a dilated vessel with a thickened wall, which was confirmed by D2-40 immunostaining to represent a lymphatic vessel. The lumen was occluded by organized thrombus, within which new vessels were being formed, indicating recanalization. In two other biopsies, similar lymphatic vessels with thickened walls were present, although the lumen of the vessels was not visualized in the planes of the section. The other four biopsies do not show specific features. Conclusion: Although only one case, this is the first pathological evidence of thrombosis within a confirmed lymphatic vessel from a case of cording. We propose that the axillary cord represents lymphatic vessel thrombosis. Recanalization of the thrombus may eventually restore lymphatic flow consistent with the transient nature of the condition.
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| 10. |
- Karlsson, Jenny, et al.
(författare)
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Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.
- 2014
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 53:5, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state. © 2014 Wiley Periodicals, Inc.
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