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showing 10 items of 2844 documents
Surmounting limited gene delivery into primary immune cell populations: Efficient cell type-specific adenoviral transduction by CAR.
2015
Ectopic gene expression studies in primary immune cells have been notoriously difficult to perform due to the limitations in conventional transfection and viral transduction methods. Although replication-defective adenoviruses provide an attractive alternative for gene delivery, their use has been hampered by the limited susceptibility of murine leukocytes to adenoviral infection, due to insufficient expression of the human coxsackie/adenovirus receptor (CAR). In this issue of the European Journal of Immunology, Heger et al. [Eur. J. Immunol. 2015. 45: XXXX-XXXX] report the generation of transgenic mice that enable conditional Cre/loxP-mediated expression of human CAR. The authors demonstra…
C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation
2015
Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mi…
Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohor…
2015
Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the i…
EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arte…
2010
EULAR/PRINTO/PRES Objectives To validate the previously proposed classification criteria for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA).Methods Step 1: retrospective/prospective webdata collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis <= 18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and.-agreement) and nominal group technique consensus evaluations.Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compar…
Second generation sequencing of three STRs D3S1358, D12S391 and D21S11 in Danes and a new nomenclature for sequenced STR alleles
2014
Second generation sequencing (SGS) may revolutionize the field of forensic STR typing. Two of the essential requirements for implementation of an SGS based approach for forensic investigations are (1) establishment of adequate frequency databases and (2) adoption of a new STR nomenclature. We report the STR sequences and allele frequencies of three STR loci: D3S1358, D12S391 and D21S11 in 197 unrelated Danes. We used a new STR nomenclature that depicts the locus name used in forensic genetics, the length of the repeat region divided by the repeat length (typically 4 nucleotides) and detailed sequence information of possible sub-repeats and SNPs within the amplified fragment.
Considerations from the European DNA profiling group (EDNAP) concerning STR nomenclature
1997
(1) The nomenclature of any STR follows from comparison with a control allelic ladder; availability of reference allelic ladders is central to any scheme. The components of an allelic ladder should be sequenced. (2) The DNA commission recommended a nomenclature based upon the number of repeat sequences present in an allele. Whereas this method is suitable for typing simple STRs, complex hypervariable repeats such as ACTBP2 do not conform to a simple repeating structure. We propose that designation of complex STR repeats such as ACTBP2, D11S554 and APOAI1 follows from the size of specific alleles. Because the size is dependant upon the primers utilised, the size is not definitive (it may als…
Does the VP1 gene of foot-and-mouth disease virus behave as a molecular clock?
1992
We have carried out a phylogenetic study of the evolution of the VP1 gene sequence from different serological types and subtypes of foot-and-mouth disease virus (FMDV). The maximum-likelihood method developed by Hasegawa and co-workers (Hasegawa et al. 1985) for the estimation of evolutionary parameters and branching dates has been used to decide between alternative models of evolution: constant versus variable rates. The results obtained indicate that a constant rate model, i.e., a molecular clock, seems to be the most plausible one. However, additional information suggests the possibility that the appearance of serotype CS has been accompanied by an episode of rapid evolution (Villaverde …
Some notes on the geographical distribution of the human red cell acid phosphatase phenotypes
1972
Basing on the data of 65 populations the geographical variability of the human red cell acid phosphatase phenotypes resp. alleles was studied. We found a marked distribution gradient: The frequency of pB-alleles increases with the increase of the mean annual temperature of the various biotops, whereas the pA-allele frequencies show a clear decrease. For this allele we calculated a significant negative correlation between its frequency and the mean annual temperature: r=-0.71; P<0.001. We suppose that the pB-allele is in some way adaptive under the climatic conditions of tropical biotops. The possible reasons are discussed.
Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
2007
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability. However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN. A major candidate is represe…
Reducing treatment duration in patients infected with hepatitis C genotype 1: any need for further studies?
2009
The recommended treatment duration with pegylated interferon-α plus ribavirin for patients infected with hepatitis C virus (HCV) genotype 1 is 48 weeks. Interestingly, a subpopulation of genotype 1 patients experience rapid decreases in HCV RNA levels once treatment is initiated and attain rapid virological response, defined as undetectable HCV RNA at week 4 of therapy. Several studies have shown that these patients can be effectively treated for a 24-week period without any significant decreases in sustained virological response rates. The aim of this review was to consider the existing clinical evidence regarding the use of a 24-week treatment schedule among genotype 1 patients and to hi…