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Zhu L.,Chinese PLA General Hospital | Pan J.,Chinese PLA General Hospital | Wei C.,Chinese PLA General Hospital | Wang H.,Chinese PLA General Hospital | And 3 more authors.
Transfusion | Year: 2015

Background A flow-based treatment device using riboflavin and ultraviolet (UV) light was developed to inactivate viruses in fresh-frozen plasma (FFP). The objective of this study was to evaluate the in vitro effectiveness of virus inactivation and changes in protein quality in FFP treated with this device. Study Design and Methods FFP-contaminating viruses were treated with riboflavin and UV light using a one-pass linear flow device. The infectivity of viruses was measured using established biologic assays. Real-time polymerase chain reaction (PCR) was performed to detect damage to viral nucleotides after treatment. Treated plasma was analyzed using standard coagulation assays. Results FFP treated at the UV dose of 3.6 J/cm2 (J) exhibited a mean reduction of virus titer of more than 4 logs. The effectiveness increased significantly at higher doses. Real-time PCR showed that the cycle threshold values for both complete inactivation and virus recultivation were higher than that of the untreated sample. At doses of 3.6, 5.4, and 7.2 J, the protein recovery rates were 60.2 ± 8.6, 46.6 ± 9.4, and 28.0 ± 1.0% for fibrinogen; 67.0 ± 3.1, 57.3 ± 8.0, and 49.2 ± 3.8% for Factor VIII; 93.6 ± 2.8, 89.6 ± 6.1, and 86.5 ± 5.3% for antithrombin-III; and 72.1 ± 5.6, 59.8 ± 14.2, and 49.2 ± 8.4% for Protein C, respectively. Conclusion The effectiveness of virus inactivation was enhanced, but total activity of plasma factors was reduced, in a UV dose-dependent manner. © 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Zhang X.,Uppsala University | Wang B.,Uppsala University | Wang B.,Beijing Institute of Pharmacology and Toxicology | O'Callaghan P.,Uppsala University | And 11 more authors.
Acta Neuropathologica | Year: 2012

Neuroinflammation is typically observed in neurodegenerative diseases such as Alzheimer's disease, as well as after traumatic injury and pathogen infection. Resident immune cells, microglia and astrocytes, are activated and joined by blood-borne monocytes that traverse the blood-brain barrier and convert into activated macrophages. The activated cells express various cytokines, chemokines and proteolytic enzymes. To study the role of heparan sulfate proteoglycans in neuroinflammation, we employed a transgenic mouse overexpressing heparanase, an endoglucuronidase that specifically degrades heparan sulfate side chains. Neuroinflammation was induced by systemic challenge with lipopolysaccharide, or by localized cerebral microinjection of aggregated amyloid-β peptide, implicated in Alzheimer's disease. Lipopolysaccharide- treated control mice showed massive activation of resident microglia as well as recruitment of monocyte-derived macrophages into the brain parenchyma. Microinjection of aggregated amyloid- β elicited a similar inflammatory response, albeit restricted to the injection site, which led to dispersion and clearance of the amyloid. In the heparanase-overexpressing mice, all aspects of immune cell recruitment and activation were significantly attenuated in both inflammation models, as was amyloid dispersion. Accordingly, an in vitro blood- brain barrier model constructed from heparanase-overexpressing cerebral vascular cells showed impaired transmigration of monocytes compared to a corresponding assembly of control cells. Our data indicate that intact heparan sulfate chains are required at multiple sites to mediate neuroinflammatory responses, and further point to heparanase as a modulator of this process, with potential implications for Alzheimer's disease. © Springer-Verlag 2012.

Hiemann N.E.,Deutsches Herzzentrum Berlin | Meyer R.,Deutsches Herzzentrum Berlin | Wellnhofer E.,Deutsches Herzzentrum Berlin | Schoenemann C.,Institute of Transfusion Medicine | And 4 more authors.
Transplantation | Year: 2012

BACKGROUND: Non-human leukocyte antigen antibodies (Abs) targeting vascular receptors are implicated in the pathogenesis of renal allograft vascular rejection and in progressive vasculopathy in patients with systemic sclerosis. METHODS: We prospectively tested in 30 heart transplant recipients the impact of Abs directed against endothelin-1 type A (ETAR) and angiotensin II type 1 receptors (AT1R, cell-enzyme-linked immunosorbent assay) at time of transplantation and during the first posttransplantation year on cellular and Ab-mediated rejection (immunohistochemistry, C3d, and immunoglobulins) and microvasculopathy in endomyocardial biopsy. RESULTS: Cellular rejection, Ab-mediated rejection, and microvasculopathy was found in 40% and 13%, 57% and 18%, and 37% and 40% of biopsies at 1 month and 1 year posttransplantation, respectively. Maximum levels of AT1R and ETAR Abs were higher in patients with cellular (16.5±2.6 vs. 9.4±1.3; P=0.021 and 16.5±2.5 vs. 9.9±1.9; P=0.041) and Ab-mediated rejection (19.0±2.6 vs. 10.0±1.3; P=0.004 and 19.4±2.7 vs. 9.0±1.7; P=0.002), as compared with patients who had no rejection. Patients with elevated AT1R Abs (53% [16/30]) or ETAR Abs (50% [15/30]; pretransplantation prognostic rejection cutoff >16.5 U/L) presented more often with microvasculopathy (both, 67% vs. 23%; P=0.048) than patients without. CONCLUSIONS: Elevated levels of AT1R and ETAR Abs are associated with cellular and Ab-mediated rejection and early onset of microvasculopathy and should be routinely monitored after heart transplantation. © 2012 by Lippincott Williams & Wilkins.

Parkner A.M.,Institute of Transfusion Medicine | Halm-Heinrich I.,Institute of Transfusion Medicine | Hahn J.,Institute of Transfusion Medicine | Heim M.U.,Institute of Transfusion Medicine
Tissue Antigens | Year: 2012

The newly detected HLA-B*15:238 is distinguished from HLA-B*15:52 by a single-nucleotide exchange at position 527 where T is replaced by A. © 2012 John Wiley & Sons A/S.

Yin H.-Q.,Institute of Transfusion Medicine | Xiao R.,Beijing Institute of Radiation Medicine | Rong Z.,Beijing Institute of Radiation Medicine | Jin P.-P.,Institute of Transfusion Medicine | And 2 more authors.
Methods | Year: 2015

The evanescent wave fiber immunosensors (EWFI) technique was developed for the real-time rapidly sensitive and specific detection of the monoclonal antibody 3E2 of BTV. The outer-core protein VP7 of BTV was labled on the surface of the exposed fiber-optic core. The monoclonal antibody 3E2 of BTV VP7 were added and then the goat ant-rat IgG conjugated with Cy3 was captured. After the 532. nm pulse (excitation source) reached the fiber probe, evanescent wave was generated, which excited the Cy3 bound to the immuno-complex and produced the fluorescent signal, which was changed into electrical signals read through computer. The preliminary results suggested that a detection limit of 10. ng/ml was measured for the monoclonal antibody 3E2, which is equal to the sensitivity of ELISA. The 3E2 sample was specifically detected through the EWFI assay in 15. min, and the fiber can be recycled at least ten times through TEA solution condition. This developed EWFI was a real-time rapidly sensitive and specific way for the detection of BTV antibodies. © 2015.

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