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  • 1
    Publication Date: 2018-09-07
    Description: von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.
    Keywords: Thrombosis and Hemostasis, Vascular Biology
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2018-05-15
    Description: H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKG KRTA R/G, PKG KRIA R/G, PKR KRAA R/G, and PKR KRTA R/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5. IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 3
    Publication Date: 2018-02-27
    Description: The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control. IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  45. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 19. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC), 52. Jahrestagung der Österreichischen Gesellschaft für Plastische, Ästhetische und Rekonstruktive Chirurgie (ÖGPRÄC); 20140911-20140913; München; DOC316 /20140903/
    Publication Date: 2014-09-04
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC); 20130526-20130529; Düsseldorf; DOCP 015 /20130521/
    Publication Date: 2013-05-22
    Keywords: Antibiotic prophylaxis ; Surgical site infection ; Third-generation cephalosporin ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    Keywords: DISEASE ; DISEASES ; GENE ; GENES ; PROTEIN ; PROTEINS ; RNA ; DNA ; recombination ; tumour ; BIOLOGY ; SEQUENCE ; chromosome ; NUMBER ; MUTATION ; inactivation ; REGION ; MUTATIONS ; EVOLUTION ; DEGRADATION ; CHROMOSOMES ; GENE FAMILY ; AID ; HUMAN GENOME SEQUENCE ; INACTIVATION CENTER ; LINKED MENTAL-RETARDATION ; MAMMALIAN Y-CHROMOSOME ; REPEAT HYPOTHESIS
    Abstract: The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence
    Type of Publication: Journal article published
    PubMed ID: 15772651
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  • 7
    Keywords: OPTIMIZATION ; APOPTOSIS ; CELLS ; proliferation ; INHIBITION ; VOLUME ; INDUCTION ; FLOW ; PARAMETERS ; CAPACITY ; PH ; FLAVONOIDS ; RECOVERY ; SEPARATION ; adsorption ; PEOPLE ; DESORPTION ; ANTHOCYANINS ; luteolin ; macroporous resins ; pigeonpea ; POLYMERIC ADSORBENTS
    Abstract: In the present study, the performance and separation characteristics of eight macroporous resins for the separation of luteolin (LU) from pigeonpea leaves extracts have been evaluated. The adsorption and desorption properties of LU on macroporous resins including AB-8, NKA-9, NKA-2, D3520, D101, H 1020, H103 and AL-2 have been compared. AL-2 resin offers the best adsorption and desorption capacity for LU than other resins based on the research results, and its adsorption data at 25 degrees C fit best to the Freundlich isotherm. Dynamic adsorption and desorption experiments have been carried out with the column packed by AL-2 resin to optimize the separation process of LU from pigeonpea leaves extracts. The optimum parameters for adsorption were sample solution LU concentration 65.5 mu g/ml, pH 5, processing volume 3 BV, flow rate 1.5 BV/h, temperature 25 degrees C; for desorption were elution solvent ethanol-water (50:50, v/v) 2 BV and followed by ethanol-water (60:40, v/v) 2 BV, and flow rate I BV/h. After treated with AL-2 resin, the LU content in the product was increased 19.8-fold from 0.129% to 2.55%, with a recovery yield of 78.54%. The results showed that AL-2 resin revealed a good ability to separate LU. Therefore, we conclude that results in this study may provide scientific references for the large-scale LU production from pigeonpea or other plants extracts. (c) 2006 Elsevier B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17126843
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  • 8
    Keywords: CELLS ; AGENTS ; CELL ; Germany ; MICROSCOPY ; THERAPY ; DEATH ; TIME ; MECHANISM ; mechanisms ; treatment ; DAMAGE ; SURFACE ; MORPHOLOGY ; BODY ; AGENT ; BODIES ; CHEMISTRY ; HEIGHT ; LEVEL ; SIZE ; technique ; pharmacology ; ANTIBACTERIAL ; Atomic force microscopy ; SHAPE ; antibacterial activity ; CYTOPLASM ; essential oil ; GRAM-POSITIVE BACTERIA ; labiatae ; Propionibacterium acnes ; rosemary ; rosmarinus officinalis L ; VULGARIS
    Abstract: In the present study, the antibacterial activity of rosemary (Rosmarinus officinalis L. Labiatae) essential oil against Propionibacterium acnes (P. acnes) was observed with atomic force microscopy (AFM). The MIC (minimal inhibitory concentration) value of rosemary essential oil against Racnes was 0.56 mg/mL. Significant changes in morphology and size of P. acnes were observed by atomic force microscopy (AFM) in response to essential oil treatment. The essential oil first attached to the surface of A acnes at low concentration, the width and height of the bacterial body became larger, whereas the length did not change considerably. With increasing concentration of the essential oil, the bacterial bodies were severely damaged. The length, width and height were all reduced, when the concentration was increased up to 64 x MIC, the length, width and height were reduced by 42.56%, 92.00% and 41.58%, respectively. Furthermore, treated bacteria lost their native shape, the cell wall desquamated, and the cytoplasm leaked out of the bacterial body, finally leading to bacterial death. With the increasing time at MIC, the bacteria length was reduced at 8 h, the width and height gradually became smaller, the shape of the cell became distorted, and finally led to cell wall damage and bacterial death at 8 h. In conclusion, the AFM investigation of morphology and size of A acnes treated with rosemary essential oil represents a powerful technique, which can generally be applied to reveal the biological changing mechanisms of bacteria induced by antibacterial agents at the nanometer level
    Type of Publication: Journal article published
    PubMed ID: 17893831
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  • 9
    Keywords: ENVIRONMENT ; CANCER ; carcinoma ; CELL ; neoplasms ; COMMON ; incidence ; POPULATION ; GENE ; GENES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; FREQUENCIES ; cytokines ; DISTRIBUTIONS ; DIFFERENCE ; PROMOTER ; AGE ; SWEDEN ; LENGTH ; POPULATIONS ; HEALTHY ; basal cell carcinoma ; CYCLIN D1 ; CELL CARCINOMA ; WORLDWIDE ; ALLELE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; RHEUMATOID-ARTHRITIS ; REDUCTASE ; INTERLEUKIN-6 ; BCC ; interleukin gene ; METHYLENETETRAHYDROFOLATE REDUCTASE ; MTHFR ; SINGLE-NUCLEOTIDE POLYMORPHISMS
    Abstract: Background: Pyrosequencing is a new method to detect single nucleotide polymorphisms (SNPs). Basal cell carcinoma (BCC) is one of the most common neoplasms in the world, and its incidence has been increasing worldwide in recent years. BCC is caused by an interplay between genetic and environment factors. Methods: Pyrosequencing and restrict fragment length polymorphism (RFLP) were used in the study. We conducted a case-control association study in BCC cases and controls from Sweden. For SNPs in IL-6, IL-10 andIL-1beta, 241 cases were at the age of 27-70 years (mean 50 years) and 260 healthy controls were 26-71 years (mean 48 years), 241 cases were 27-70 years (mean 50 years) and 574 healthy controls were 22-74 years (mean 52 years) for cyclin D1 G870A, 197 cases were 29-69 years (mean 47 years) and 574 healthy controls were 22-74 years (mean 52 years) for MTHFR C677T and A1298C. Nine SNPs for IL-6-174G/C, -634G/C and -597G/A; IL-10-1082G/A and -592C/A; IL-1beta-511CIT; cyclin D1 G870A; MTHFR C677T and A1298C were analyzed. Results: Most genotype distributions were in accordance with Hardy-Weinberg equilibrium (HWE), except IL-10-1082G/A, which had a significantly deviation from HWE in BCC cases (P〈0.05). Linkage disequilibrium was observed between the -174 and -597 alleles in the IL6 gene in the studied populations. The differences for cyclin D1 G870A and methylenetetrahydrofolate reductase (MTHFR) C677T were found between BCC cases group and control group (P〈0.05, OR=1.34, 95% CI, 1.00-1.74; P〈0.05, OR=1.67, 95% CI, 1.13-2.47, respectively). Conclusions: Cyclin DI G870A and MTHFR C677T were associated with BC cases from Sweden, the other SNPs studied here were not associated with BCC, but chance cannot be excluded. (C) 2004 Elsevier B.V All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15026274
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  • 10
    Keywords: DRUG ; HPLC ; ASSAY ; CARCINOMA CELLS ; TANDEM MASS-SPECTROMETRY ; PURIFICATION ; LIQUID-CHROMATOGRAPHY ; 10-deacetylbaccatin III ; CULTURES ; HIMALAYAN YEW ; PACLITAXEL TAXOL ; PFP column ; taxoids ; Taxus ; WALLICHIANA
    Abstract: A simple and accurate RP-HPLC method with pentafluorophenyl (PFP) column was developed for the simultaneous determination of six taxoids, i.e. paclitaxel, 10-deacetylbaccatin III (10-DAB III), 7-xylosyl-10-deacetyltaxol (7-xyl-10-DAT), 10-deacetyltaxol (10-DAT), cephalomannine and 7-epi-10-deacetyltaxol (7-epi-10-DAT), In the extracts from the needles of three Taxus species. The mobile phase consisted of acetonitrile (A) and water (B), and the extracts were separated using gradient elution program: 30% A at the first 7 min, and then ramped to 42% A at 8 min, held until 38 min. The developed method was validated with satisfactory precision (RSD 〈 2.61%), repeatability (RSD 〈 2.92%) and recovery (95.19-104.47%). The above taxoids in the extracts of Tamus cuspidata, T. chinensis and T. media were analyzed with the developed RP-HPLC method, and the results showed that the contents of different taxoids in three mentioned species were distinct. Maximal amounts of 10-DAB III, 7-xyl-10-DAT and 7-epi-10-DAT appeared in T. chinensis, while T. media possessed the highest content of 10-DAT, cephalomannine and paclitaxel. The developed method is accurate and efficient. It can be reliably used in the improved determination of taxoids for the quality control of Taxus species. Copyright (c) 2008 John Wiley & Sons, Ltd
    Type of Publication: Journal article published
    PubMed ID: 18816506
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