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- Hellquist, H. B., et al.
(författare)
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Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12
- 1996
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Ingår i: Virchows Archiv. - New York, USA : Springer. - 0945-6317 .- 1432-2307. ; 429:2-3, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.
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- Davidsson, Åke, 1956-, et al.
(författare)
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Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy
- 1996
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Ingår i: Acta Oto-Laryngologica. - Oxfordshire, United Kingdom : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 116:4, s. 604-610
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Tidskriftsartikel (refereegranskat)abstract
- Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.
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- Olofsson, A M, et al.
(författare)
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Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis
- 1999
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 104:7, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil-borne heparin-binding protein (HBP) is a multifunctional protein involved in the progression of inflammation. HBP is stored in neutrophil granules and released upon stimulation of the cells in proximity to endothelial cells. HBP affects endothelial cells in multiple ways; however, the molecular and cellular mechanisms underlying the interaction of HBP with these cells are unknown. Affinity isolation and enzymatic degradation demonstrated that HBP released from human neutrophils binds to endothelial cell-surface proteoglycans, such as syndecans and glypican. Flow cytometry indicated that a significant fraction of proteoglycan-bound HBP is taken up by the endothelial cells, and we used radiolabeled HBP to determine the internalization rate of surface-bound HBP. Confocal and electron microscopy revealed that internalized HBP is targeted to perinuclear compartments of endothelial cells, where it colocalizes with mitochondria. Western blotting of isolated mitochondria from HBP-treated endothelial cells showed that HBP is present in 2 forms - 28 and 22 kDa. Internalized HBP markedly reduced growth factor deprivation-induced caspase-3 activation and protected endothelial cells from apoptosis, suggesting that uptake and intracellular routing of exogenous HBP to mitochondria contributes to the sustained viability of endothelial cells in the context of locally activated neutrophils.
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- Olofsson, B, et al.
(författare)
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Vascular endothelial growth factor B, a novel growth factor for endothelial cells
- 1996
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 93:6, s. 2576-2581
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Tidskriftsartikel (refereegranskat)abstract
- We have isolated and characterized a novel growth factor for endothelial cells, vascular endothelial growth factor B (VEGF-B), with structural similarities to vascular endothelial growth factor (VEGF) and placenta growth factor. VEGF-B was particularly abundant in heart and skeletal muscle and was coexpressed with VEGF in these and other tissues. VEGF-B formed cell-surface-associated disulfide-linked homodimers and heterodimerized with VEGF when coexpressed. Conditioned medium from transfected 293EBNA cells expressing VEGF-B stimulated DNA synthesis in endothelial cells. Our results suggest that VEGF-B has a role in angiogenesis and endothelial cell growth, particularly in muscle.
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- Suhr, O B, et al.
(författare)
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Impact of autonomic neuropathy on circulatory instability during liver transplantation for familial amyloidotic polyneuropathy.
- 1997
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 63:5, s. 675-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Circulatory instability with severe hypotension frequently complicates liver transplantation in patients with familial amyloidotic polyneuropathy. Autonomic dysfunction is found early in the course of the disease by analysis of beat-to-beat heart rate variability (HRV). The aim of the present study was to investigate the impact of autonomic neuropathy on intraoperative circulatory instability during liver transplantation for familial amyloidotic polyneuropathy.METHODS: Twenty-two patients were evaluated at the Department of Medicine, Umea University Hospital, by spectral analysis of HRV and later received liver transplants at Huddinge University Hospital. The low-and high-frequency bands obtained by spectral analysis of HRV in the supine and upright positions, respectively, were used as representative of sympathetic and parasympathetic activity. Circulatory instability during transplantation was defined as a fall in systolic arterial blood pressure below 70 mmHg for more than 5 min during the preanhepatic phase.RESULTS: Both arrhythmia preventing spectral analysis of HRV and a sympathetic variability peak below 2.5 mHz2 were significantly more common among patients with intraoperative circulatory instability (P=0.03 and 0. 004, respectively). A diminished increase in pulse rate when tilting the patients from the supine to the upright position was also more pronounced among patients with circulatory instability (P<0.05).CONCLUSIONS: The majority of patients who will develop circulatory instability with a pronounced fall in arterial blood pressure can be identified by Poincare plots of R-R intervals and spectral analysis of HRV. A low sympathetic peak or arrhythmia precluding spectral analysis of HRV is significantly related to operative circulatory instability.
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