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41.
Annemarie Brüel Jens R Nyengaard Carl Christian Danielsen 《Growth hormone & IGF research》2006,16(3):193-201
In cardiac hypertrophy induced by GH, the turn-over of collagen seems to be increased. Matrix metalloproteinases (MMP) are enzymes suggested to contribute to the remodelling of the extracellular matrix in the myocardium. The aim of the present experiment was to investigate how GH influenced MMP concentration, collagen concentration, and structure of the connective tissue of the LV in young rats in relation to time. Three-month-old female rats were injected with GH (5mg/kg/day) or vehicle for 5, 10, 20, 40, or 80 days. MMPs and structural changes of the connective tissue were analysed using zymography and stereology, respectively. Wet weight of the LV was increased time-dependently by GH (r = 0.89, P < 0.001). Furthermore, GH increased the MMP-2 concentration (P < 0.01, two-way ANOVA), whereas no collagenases (MMP-1, MMP-8, or MMP-13) could be demonstrated. The increase in MMP-2 was accompanied by a time-dependent decrease in the collagen concentration (r = -0.46, P < 0.05), whereas the total collagen content (r = 0.85, P < 0.01) and total number of non-myocyte nuclei (GH: r = 0.89, P < 0.001) were time-dependently increased. These results indicate that MMP-2 may be involved in the remodelling process of the extracellular matrix in GH-induced cardiac hypertrophy. 相似文献
42.
Jolien Suurmond Jurgen van Heemst Jacqueline van Heiningen Annemarie L. Dorjée Marco W. Schilham Feddo B. van der Beek Tom W.J. Huizinga Annemie J.M. Schuerwegh René E.M. Toes 《European journal of immunology》2013,43(7):1758-1768
Mast cells (MCs) are immune cells residing in tissues where pathogens are first encountered. It has been indicated that MCs might also be involved in setting the outcome of T‐cell responses. However, little is known about the capacity of human MCs to express MHC class II and/or to capture and present antigens to CD4+ T cells. To study the T‐cell stimulatory potential of human MCs, CD34+ stem cell derived MCs were generated. These cells expressed HLA‐DR when stimulated with IFN‐γ, and, importantly, presented peptide and protein for activation of antigen‐specific CD4+ T cells. The interplay between MC and T cell led to increased HLA‐DR expression on MCs. MCs were present in close proximity to T cells in tonsil and expressed HLA‐DR and CD80, indicating their ability to present antigens to CD4+ T cells in T‐cell areas of human LNs. Our data show that MCs can present native antigens to human CD4+ T cells and that HLA‐DR expressing MCs are present in tonsil tissue, indicating that human MCs can directly activate T cells and provide a rationale to study the potential of MCs to prime and/or skew human T‐cell responses. 相似文献
43.
Christoph Stephan Valentin Bartha Eva Herrmann Nils von Hentig Pavel Khaykin Gaby Knecht Peter Gute Hans-Reinhard Brodt Martin Stürmer Annemarie Berger Markus Bickel 《Medical microbiology and immunology》2013,202(2):117-124
To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for >36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always <50 copies/ml (1), 50–199 copies/ml (2), 200–499 copies/ml (3) and ≥500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm3, HIV-1 RNA was 5.13 Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients were assigned by 43, 30, 7 and 20 % to groups 1–4. Median observation time was 136 weeks (range: 38–304); at weeks 48/96, the CD4-cell gains for groups 1–4 were +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data in a linear fixed effect model, ascending CD4 slopes were continuously increasing for group 1, similarly for 2 and clearly decreasing for 3–4 (p = 0.0006). Of 25 individuals from group 4, patient number with major IAS-USA protease mutations increased from 5 to 10 before and after failing PI therapy, whereas minor mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell increases through week 96 were similar for patients at always undetectable or with detection of low viral load. Viral detection >200 copies/ml was associated with decreasing CD4-cell slopes and emergence of major mutations, supporting this as benchmark for virological failure definition on PI therapy. 相似文献
44.
Alexander Seiler Annemarie Brandhofe Ren-Maxime Gracien Waltraud Pfeilschifter Elke Hattingen Ralf Deichmann Ulrike Nth Marlies Wagner 《Journal of cerebral blood flow and metabolism》2021,41(1):67
Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values (P = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased (P = 0.0001) and correlated negatively with increase of qT2 (P < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased (P < 0.01) and negatively correlated with changes of parenchymal rCPP (P = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy. 相似文献
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46.
Eric Röhner Paula Hoff Timo Gaber Annemarie Lang Pauline Vörös Frank Buttgereit 《Journal of investigative surgery》2015,28(1):1-7
Purpose/Aim of the study: Chlorhexidine and polyhexanide are frequently used antiseptics in clinical practice and have a broad antimicrobial range. Both antiseptics are helpful medical agents for septic wound treatment with a high potential for defeating joint infections. Their effect on human osteoblasts has, so far, not been sufficiently evaluated. The aim of this study was to investigate the activating potential of polyhexanide and chlorhexidine on inflammatory cytokines/chemokines in human osteoblasts in vitro. Materials and Methods: Human osteoblasts were isolated and cultivated in vitro and then treated separately with 0.1% and 2% chlorhexidine and 0.04% polyhexanide as commonly applied concentrations in clinical practice. Detection of cell structure and cell morphology was performed by light microscopic inspection. Cytokine and chemokine secretion was determined by using a multiplex suspension array. Results: Cell shrinking, defective cell membrane, and the loss of cell adhesion indicated cell damage of human osteoblasts after treatment with both antiseptics was evaluated by using light microscopy. Polyhexanide, but not chlorhexidine, caused human osteoblasts to secrete various interleukins (1β, 6, and 7), interferon γ, tumor necrosis factor α, vascular endothelial growth factor, eotaxin, fibroblast growth factor basic, and granulocyte macrophage colony-stimulating factor as quantified by multiplex suspension array. Conclusions: Both antiseptics induced morphological cell damage at an optimum exposure between 1 and 10 min. But only polyhexanide mediated a pronounced secretion of inflammatory cytokines and chemokines in human osteoblasts. Therefore, we recommend a preferred usage of chlorhexidine in septic surgery to avoid the induction of an inflammatory reaction. 相似文献
47.
The primary plasminogen-activator inhibitors in endothelial cells, platelets, serum, and plasma are immunologically related. 总被引:19,自引:3,他引:19 下载免费PDF全文
L A Erickson C M Hekman D J Loskutoff 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(24):8710-8714
Monospecific antiserum to an unusually stable Mr 50,000 plasminogen-activator inhibitor (PAI) purified from cultured bovine aortic endothelial cells was employed in conjunction with reverse fibrin autography to determine whether human platelets, serum, and plasma contain immunologically related inhibitors. Reverse fibrin autography revealed the presence of a Mr 50,000 inhibitor in the platelet and serum samples but not in normal plasma. However, a Mr 50,000 inhibitor was detected in plasma obtained from individuals with increased PAI activity. In each case, treatment of the sample with the anti-inhibitor serum removed the Mr 50,000 inhibitor. The inhibitor present in each sample neutralized exogenously added tissue-type plasminogen activator in a rapid manner. Inhibition was associated with the formation of a NaDodSO4-resistant enzyme-inhibitor complex of Mr 120,000. Again, treatment of the samples with the anti-inhibitor serum removed both the inhibitory activity and the component in these samples that binds to tissue-type plasminogen activator. Thus, the rapidly acting PAI present in human platelets, serum, and patient plasma is immunologically related to the PAI synthesized by cultured bovine aortic endothelial cells. This molecule may be the physiologically relevant inhibitor of plasminogen activator in the vascular system and, as such, may serve an important role in regulating the initiation of vascular fibrinolysis. 相似文献
48.
Tihana Bicanic Christian Bottomley Angela Loyse Annemarie E. Brouwer Conrad Muzoora Kabanda Taseera Arthur Jackson Jacob Phulusa Mina C. Hosseinipour Charles van der Horst Direk Limmathurotsakul Nicholas J. White Douglas Wilson Robin Wood Graeme Meintjes Thomas S. Harrison Joseph N. Jarvis 《Antimicrobial agents and chemotherapy》2015,59(12):7224-7231
Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility. 相似文献
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