Background: Test 1 is a recently introduced technique claiming to determine Erythrocyte Sedimentation Rate (ESR) in 20 s. In contrast to the original Westergren procedure this new technique uses undiluted blood and operates at 37°C. It is hypothesized that Test 1 is in fact an erythrocyte aggregometer and does not measure any sedimentation. Methods: Test 1 results were compared to those obtained with StaRRsed, an automated ESR analyser based on the Westergren technique, and the results of both were correlated to various indices of red blood cell (RBC) aggregation, obtained with an aggrego - meter (LORCA). Measurements were made on blood from 75 patients with various rheumatic disorders. Furthermore, blood that was experimentally manipulated in order to affect RBC aggregation, i.e. by changing the hematocrit, by diminishing plasma protein concentration, by inducing hyperaggregation or by RBC rigidification, was tested on all three instruments. Results: Generally in patient blood, Test 1 results demonstrated a higher correlation with the various aggregation parameters than StaRRsed. Highest correlation (R = −0.8)) with both Test 1 and StaRRsed outcome were seen with I20, a RBC aggregation parameter directly related to the backscatter intensity. All experimentally induced changes in RBC aggregation paralleled closely those obtained with Test 1 while StaRRsed results followed a different course. Conclusions: The results obtained in this study strongly support the hypothesis that Test 1 measures only the RBC aggregation process and does not cover any of the indices directly linked to the sedimentation process as determined by the Westergren method.
To identify the gene underlying Fanconi anemia (FA) complementation group I we studied informative FA‐I families by a genome‐wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue‐dependent expression. We found a candidate, KIAA1794 on chromosome 15q25‐26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA‐I individuals. Knock‐down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient‐derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI , since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.
Background: various modifcations of the Erythrocyte Sedimentation Rate (ESR) determination have been suggested since the original Westergren procedure that has been adopted as the gold standard by the International Council for Standardization in Haematology (ICSH). Recently, an automated method, (Alifax Test 1), based on a technique completely different from Westergren, has been introduced. Material and methods: In this comparative study, ESR of blood from 680 patients with various rheumatic diseases was determined on both Test 1 and the StaRRsed automated ESR analyser which performs measurements in accordance with ICSH specifcations. Furthermore the robustness of the new technique was evaluated. Results: Direct correlation of Test 1 and StaRRsed measurements confrmed the results of previous studies: an overall correlation coeffcient of R = 0.90. However, further statistical analysis showed that, depending on the instrument that was used, in 78 samples (i.e. 11.5%) the results could lead to different treatment suggestions. Furthermore it appeared that several procedural factors could infuence the fnal Test 1 outcome. Conclusions: Due to its sensitivity for procedural variations, Test 1 measurements should be carried out under strictly standardized conditions. Especially at the higher ESR levels the Test 1 technique is, however, not a reliable alternative for the ICSH approved ‘Westergren’ method.
Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failure, hypersensitivity to DNA cross-linking agents, chromosomal instability and susceptibility to cancer. At least 12 genetic subtypes have been described (FA-A, B, C, D1, D2, E, F, G, I, J, L, M) and all except FA-I have been linked to a distinct gene. Most FA proteins form a complex that activates the FANCD2 protein via monoubiquitination, while FANCJ and FANCD1/BRCA2 function downstream of this step. The FA proteins typically lack functional domains, except for FANCJ/BRIP1 and FANCM, which are DNA helicases, and FANCL, which is probably an E3 ubiquitin conjugating enzyme. Based on the hypersensitivity to cross-linking agents, the FA proteins are thought to function in the repair of DNA interstrand cross-links, which block the progression of DNA replication forks. Here we present a hypothetical model, which not only describes the assembly of the FA pathway, but also positions this pathway in the broader context of DNA cross-link repair. Finally, the possible role for the FA pathway, in particular FANCF and FANCB, in the origin of sporadic cancer is discussed.
Abstract : The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce the Delfia Xpress for the analysis of free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester screening program for Down syndrome. Since then, others have implemented this system. In this study, we tested the equality of measurements for free β-hCG and PAPP-A between Delfia Xpress systems and one AutoDelfia system. : A total of 40 serum samples were aliquoted and stored at –20°C. Samples were analyzed by six Delfia Xpress systems and one AutoDelfia system over a time period of 2 years. : The relationships between free β-hCG and PAPP-A were excellent for the different Delfia Xpress systems (r>0.99, p<0.0001). For PAPP-A, the agreement between the main system at VUmc and five other systems was linear with slopes between 0.99 and 1.06. Similarly, agreement for free β-hCG was linear with slopes between 0.99 and 1.09. Likewise, agreement for PAPP-A and free β-hCG was excellent for the AutoDelfia vs. the main Delfia Xpress at the VUmc (r>0.99, p<0.0001). For both PAPP-A and free β-hCG, the relationships were linear with slopes of 1.08 and 1.07. : We demonstrate an excellent agreement for the analysis of PAPP-A and free β-hCG between Delfia Xpress systems and one AutoDelfia system. Clin Chem Lab Med 2009;47:222–6.
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