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Sökning: WFRF:(Blixt O)

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  • Blixt, Christina, et al. (författare)
  • The effect of perioperative glucose control on postoperative insulin resistance
  • 2012
  • Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 31:5, s. 676-681
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Postoperative insulin resistance and the consequent hyperglycemia affects clinical outcome. Insulin sensitivity may be modulated by preoperative nutrition, adequate pain management and minimal invasive surgery. This study aims to disclose the impact of perioperative glucose control on postoperative insulin resistance.METHODS: Twenty patients scheduled for elective open hepatectomy were enrolled in this prospective, randomized study. In the treatment group (n = 9) insulin was administered intravenously to keep blood glucose between 6 and 8 mmol/l during surgery. The control group (n = 8) received insulin if blood glucose >14 mmol/l. Insulin sensitivity was measured by a hyperinsulinemic normoglycemic clamp (0.8 mU/kg/min), performed on all patients both on the day before surgery and immediately postoperatively. Plasma cortisol, insulin and C-peptide were measured.RESULTS: There was a significant difference in mean glucose value during surgery. In the control group 8.8 mmol/l (SD 1.5) vs. 6.9 mmol/l (SD 0.4) in the treated group, p = 0.003. In the control group insulin sensitivity decreased to 21.9% ± 16.2% of the preoperative value and in the insulin treated group to 46.8 ± 15.5%, p < 0.005. Insulin levels were significantly higher in the treatment group as well as consequently lower C-peptide levels.CONCLUSIONS: This trial revealed a significant difference in postoperative insulin resistance in the group treated with insulin during surgery.
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  • Goel, Suchi, et al. (författare)
  • RIFINs are adhesins implicated in severe Plasmodium falciparum malaria.
  • 2015
  • Ingår i: Nature Medicine. - : Nature Publishing Group. - 1546-170X .- 1078-8956. ; 21:4, s. 314-317
  • Tidskriftsartikel (refereegranskat)abstract
    • Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs-preferentially of blood group A-to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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  • Hinkula, Jorma, et al. (författare)
  • Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice
  • 2017
  • Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 91:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR(- / -)) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDAapproved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates.
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  • Barone, Angela, et al. (författare)
  • Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors
  • 2020
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Ovarian carcinoma is a heterogeneous disease with distinct molecular and histological profiles, ranging from low grade atypia to highly aggressive tumors associated with a poor prognosis. In the present study, glycosphingolipids were isolated from human high-grade serous ovarian carcinoma, whereby the novel stem cell marker Sialyl-lactotetra (S-Lc(4)) was characterized in two out of three cases. The presence and level of S-Lc(4)was further evaluated immunohistochemically in a cohort of patients with ovarian tumors ranging from benign lesions to high grade serous carcinoma (n= 478). Its expression was assessed in association with tumor grade, stage, histology, and survival. The data showed that S-Lc(4)is most common and highly expressed in borderline type tumors and carcinomas with low levels of aggressiveness, such as mucinous, endometrioid, and low grade serous. Accordingly, S-Lc(4)-positivity was associated with better disease-free survival. The expression of S-Lc(4)was seemingly associated with lineage continuity and could be traced from premalignant lesions to carcinoma, suggesting inheritance by a stem cell lineage that gives rise to generally indolent tumors.
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  • Clo, E., et al. (författare)
  • Characterization of the Viral O-Glycopeptidome: a Novel Tool of Relevance for Vaccine Design and Serodiagnosis
  • 2012
  • Ingår i: Journal of Virology. - 0022-538X. ; 86:11, s. 6268-6278
  • Tidskriftsartikel (refereegranskat)abstract
    • Viral envelope proteins mediate interactions with host cells, leading to internalization and intracellular propagation. Envelope proteins are glycosylated and are known to serve important functions in masking host immunity to viral glycoproteins. However, the viral infectious cycle in cells may also lead to aberrant glycosylation that may elicit immunity. Our knowledge of immunity to aberrant viral glycans and glycoproteins is limited, potentially due to technical limitations in identifying immunogenic glycans and glycopeptide epitopes. This work describes three different complementary methods for high-throughput screening and identification of potential immunodominant O-glycopeptide epitopes on viral envelope glycoproteins: (i) on-chip enzymatic glycosylation of scan peptides, (ii) chemical glycopeptide microarray synthesis, and (iii) a one-bead-one-compound random glycopeptide library. We used herpes simplex virus type 2 (HSV-2) as a model system and identified a simple O-glycopeptide pan-epitope, (501)PPA(GalNAc)TAPG(507), on the mature gG-2 glycoprotein that was broadly recognized by IgG antibodies in HSV-2-infected individuals but not in HSV-1-infected or noninfected individuals. Serum reactivity to the extended sialyl-T glycoform was tolerated, suggesting that self glycans can participate in immune responses. The methods presented provide new insight into viral immunity and new targets for immunodiagnostic and therapeutic measures.
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