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Sökning: WFRF:(Bang Bo)

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1.
  • d'Amore, Francesco, et al. (författare)
  • Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
  • 2010
  • Ingår i: British Journal of Haematology. - Federation of European Neuroscience Societies and Blackwell Publishing Ltd. - 0007-1048. ; 150:5, s. 565-573
  • Tidskriftsartikel (refereegranskat)abstract
    • P>The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.
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2.
  • Bang, Charlotte Sahlberg, 1967-, et al. (författare)
  • Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).
  • 2014
  • Ingår i: Microbial Pathogenesis. - London : Elsevier. - 0882-4010 .- 1096-1208. ; 66, s. 29-35
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.</p>
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3.
  • Bang, Charlotte Sahlberg, 1967-, et al. (författare)
  • The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide
  • 2014
  • Ingår i: BMC Microbiology. - London : BioMed Central. - 1471-2180 .- 1471-2180. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong>: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin.</p><p><strong>Results</strong>: Four clinical isolates of multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h.</p><p><strong>Conclusion</strong>: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.</p>
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4.
  • d'Amore, Francesco, et al. (författare)
  • Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
  • 2010
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.</p>
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5.
  • Faucherre, Samuel, et al. (författare)
  • Short and Long-Term Controls on Active Layer and Permafrost Carbon Turnover Across the Arctic
  • 2018
  • Ingår i: Journal of Geophysical Research - Biogeosciences. - American Geophysical Union (AGU). - 2169-8953. ; 123:2, s. 372-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Decomposition of soil organic matter (SOM) in permafrost terrain and the production of greenhouse gases is a key factor for understanding climate change-carbon feedbacks. Previous studies have shown that SOM decomposition is mostly controlled by soil temperature, soil moisture, and carbon-nitrogen ratio (C:N). However, focus has generally been on site-specific processes and little is known about variations in the controls on SOM decomposition across Arctic sites. For assessing SOM decomposition, we retrieved 241 samples from 101 soil profiles across three contrasting Arctic regions and incubated them in the laboratory under aerobic conditions. We assessed soil carbon losses (Closs) five times during a 1 year incubation. The incubated material consisted of near-surface active layer (ALNS), subsurface active layer (ALSS), peat, and permafrost samples. Samples were analyzed for carbon, nitrogen, water content, δ13C, δ15N, and dry bulk density (DBD). While no significant differences were observed between total ALSS and permafrost Closs over 1 year incubation (2.3 ± 2.4% and 2.5 ± 1.5% Closs, respectively), ALNS samples showed higher Closs (7.9 ± 4.2%). DBD was the best explanatory parameter for active layer Closs across sites. Additionally, results of permafrost samples show that C:N ratio can be used to characterize initial Closs between sites. This data set on the influence of abiotic parameter on microbial SOM decomposition can improve model simulations of Arctic soil CO2 production by providing representative mean values of CO2 production rates and identifying standard parameters or proxies for upscaling potential CO2 production from site to regional scales.
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6.
  • Faucherre, Samuel, et al. (författare)
  • Short and Long-Term Controls on Active Layer and Permafrost Carbon Turnover Across the Arctic
  • 2018
  • Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953 .- 2169-8961. ; 123:2, s. 372-390
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Decomposition of soil organic matter (SOM) in permafrost terrain and the production of greenhouse gases is a key factor for understanding climate change-carbon feedbacks. Previous studies have shown that SOM decomposition is mostly controlled by soil temperature, soil moisture, and carbon-nitrogen ratio (C:N). However, focus has generally been on site-specific processes and little is known about variations in the controls on SOM decomposition across Arctic sites. For assessing SOM decomposition, we retrieved 241 samples from 101 soil profiles across three contrasting Arctic regions and incubated them in the laboratory under aerobic conditions. We assessed soil carbon losses (C-loss) five times during a 1year incubation. The incubated material consisted of near-surface active layer (AL(NS)), subsurface active layer (AL(SS)), peat, and permafrost samples. Samples were analyzed for carbon, nitrogen, water content, C-13, N-15, and dry bulk density (DBD). While no significant differences were observed between total AL(SS) and permafrost C-loss over 1year incubation (2.32.4% and 2.51.5% C-loss, respectively), AL(NS) samples showed higher C-loss (7.94.2%). DBD was the best explanatory parameter for active layer C-loss across sites. Additionally, results of permafrost samples show that C:N ratio can be used to characterize initial C-loss between sites. This data set on the influence of abiotic parameter on microbial SOM decomposition can improve model simulations of Arctic soil CO2 production by providing representative mean values of CO2 production rates and identifying standard parameters or proxies for upscaling potential CO2 production from site to regional scales.</p>
  •  
7.
  • Faucherre, Samuel, et al. (författare)
  • Short and Long-Term Controls on Active Layer and Permafrost Carbon Turnover Across the Arctic
  • 2018
  • Ingår i: Journal of Geophysical Research - Biogeosciences. - American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 123:2, s. 372-390
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Decomposition of soil organic matter (SOM) in permafrost terrain and the production of greenhouse gases is a key factor for understanding climate change-carbon feedbacks. Previous studies have shown that SOM decomposition is mostly controlled by soil temperature, soil moisture, and carbon-nitrogen ratio (C:N). However, focus has generally been on site-specific processes and little is known about variations in the controls on SOM decomposition across Arctic sites. For assessing SOM decomposition, we retrieved 241 samples from 101 soil profiles across three contrasting Arctic regions and incubated them in the laboratory under aerobic conditions. We assessed soil carbon losses (C-loss) five times during a 1year incubation. The incubated material consisted of near-surface active layer (AL(NS)), subsurface active layer (AL(SS)), peat, and permafrost samples. Samples were analyzed for carbon, nitrogen, water content, C-13, N-15, and dry bulk density (DBD). While no significant differences were observed between total AL(SS) and permafrost C-loss over 1year incubation (2.32.4% and 2.51.5% C-loss, respectively), AL(NS) samples showed higher C-loss (7.94.2%). DBD was the best explanatory parameter for active layer C-loss across sites. Additionally, results of permafrost samples show that C:N ratio can be used to characterize initial C-loss between sites. This data set on the influence of abiotic parameter on microbial SOM decomposition can improve model simulations of Arctic soil CO2 production by providing representative mean values of CO2 production rates and identifying standard parameters or proxies for upscaling potential CO2 production from site to regional scales.</p>
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8.
  • Mahajan, Anubha, et al. (författare)
  • Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
  • 2018
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (<em>P</em> &lt; 2.2 × 10<sup>−7</sup>); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.</p>
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9.
  • Mahajan, Anubha, et al. (författare)
  • Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
  • 2018
  • Ingår i: Nature Genetics. - NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P &lt; 2.2 x 10(-7)); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio &lt;= 1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.</p>
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10.
  • Natali, Susan M., et al. (författare)
  • Large loss of CO2 in winter observed across the northern permafrost region
  • 2019
  • Ingår i: Nature Climate Change. - 1758-678X .- 1758-6798. ; 9:11, s. 852-857
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Recent warming in the Arctic, which has been amplified during the winter(1-3), greatly enhances microbial decomposition of soil organic matter and subsequent release of carbon dioxide (CO2)(4). However, the amount of CO2 released in winter is not known and has not been well represented by ecosystem models or empirically based estimates(5,6). Here we synthesize regional in situ observations of CO2 flux from Arctic and boreal soils to assess current and future winter carbon losses from the northern permafrost domain. We estimate a contemporary loss of 1,662 TgC per year from the permafrost region during the winter season (October-April). This loss is greater than the average growing season carbon uptake for this region estimated from process models (-1,032 TgC per year). Extending model predictions to warmer conditions up to 2100 indicates that winter CO2 emissions will increase 17% under a moderate mitigation scenario-Representative Concentration Pathway 4.5-and 41% under business-as-usual emissions scenario-Representative Concentration Pathway 8.5. Our results provide a baseline for winter CO2 emissions from northern terrestrial regions and indicate that enhanced soil CO2 loss due to winter warming may offset growing season carbon uptake under future climatic conditions.</p>
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