A 4-gene expression score associated with high levels of Wilms Tumor-1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia

Wilms Tumor-1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression profiles in the highest and lowest quartiles of WT1 expression in two large AML studies. Two high WT1 gene sets were found to be highly correlated in terms of the altered genes and expression profiles. We identified a 17-probe set signature of the high WT1 set as the optimal prognostic predictor in the first AML set, and showed that it was able to predict prognosis in the second AML series after adjustment for Europe

Case report: passive transfer of hepatitis B antibodies from intravenous immunoglobulin

Abstract Background: Prior to initiating immunosuppressive therapy in the treatment of autoimmune inflammatory conditions, it is a requirement to screen for certain viral serology, including hepatitis B (HBV). A positive result may indicate the need for antiviral therapy, or contraindicate immunosuppression all together. An accurate interpretation of serological markers is therefore imperative in order to treat patients appropriately. We present a case of passive anti-HBV antibody transfer following intravenous immunoglobulin (IVIg) infusion, in which misinterpretation of serology results almost led to inappropriate treatment with antiviral therapy and the withholding of immunosuppressive agents. This phenomenon has been previously reported, but awareness remains limited. Case presentation: A 50 year old Caucasian gentleman with a history of allogeneic haematopoietic stem cell transplant for transformed follicular lymphoma was admitted to hospital with recurrent respiratory tract infections. Investigation found him to be hypogammaglobulinaemic, and he was thus given 1 g/kg of intravenous immunoglobulin. The patient also disclosed a 3-week history of painful, swollen joints, leading to a diagnosis of seronegative inflammatory polyarthritis. Prior to initiating long term immunosuppression, viral screening found hepatitis B serology suggestive of past infection, with positive results for both anti-HBc and anti-HBs antibody, but negative HBV DNA. In response, prednisolone was weaned and the local hepatology team recommended commencement of lamivudine. Having been unable to identify a source of infection, the case was reported to the local blood centre, who tested a remaining vial from the same batch of IVIg and found it to be anti-HBc and anti-HBs positive. Fortunately the blood products were identified and tested prior to the patient initiating HBV treatment, and the effect of a delay in starting disease-modifying therapy was inconsequential in light of an excellent response to first-line therapies. Conclusion: Misinterpretation of serology results following IVIg infusion may lead to significant patient harm, including unnecessary antiviral administration, the withholding of treatments, and psychosocial damage. This is especially pertinent at a time when we have an ever increasing number of patients being treated with IVIg for a wide array of immune-mediated disease. Passive antibody transfer should be considered wherever unexpected serological changes are identified

The Typology of the Literary Character in E. Adamson’s Prose

Bakalaura darba „Tēlu tipoloģija E.Ādamsona prozā” pamatā ir Erika Ādamsona īsprozas un romāna „Sava ceļa gājējs” tēlu tipoloģijas analīze. Pētītas tēlu raksturīgākās īpatnības, tai skaitā arī kompleksi. Analizētas tās varoņu īpašības, kas nonākot saskarsmē ar dažādiem apstākļiem, maina cilvēka dzīves principus un pat turpmāko likteni, tēlu psiholoģija, personību raksturu veidošanās pamatprincipi. Aplūkoti jautājumi, kuriem bijusi tieša ietekme uz rakstnieka radošo procesu, atsevišķās nodaļās un apakšnodaļās analizēti cilvēku tipi E.Ādamsona novelēs, gadījuma un iedomu akcents cilvēka psihes tēlojumā, kā arī pētīti cilvēku tipi E.Ādamsona romānā „Sava ceļa gājējs”. Vērtēta E.Ādamsona oriģinalitāte prozā un prozas žanriskās piederības problēma. Atslēgas vārdi: Eriks Ādamsons, proza, tēlu tipoloģija, cilvēka psiholoģija, kompleksi.The Bachelor Paper “Typology of Personages in the Prose of E. Ādamsons” is based on the typology analysis of personages of the short prose and the novel “Sava ceļa gājējs” of Eriks Ādamsons. There are studied the most characteristic peculiarities of personages, including their complexes. There are analysed those qualities of the personages, which in different circumstances change the principles of life of a persons and even his/her further fate, psychology of personages, main principles of formation of character of personalities. There are discussed the issues which have had a great impact on the creative process of the author, in separate chapters and subchapters there are analysed the types of persons in the novels of E. Ādamsos, the accent of a chance and illusions in depiction of human psyche, as well as investigated the types of persons in the novel of E. Ādamsons „Sava ceļa gājējs”. There is assessed the originality of E. Ādamsons in prose and the problem of genre belonging of the prose. Key words: Eriks Ādamsons, prose, typology of personages, human psychology, complexes

Differential mRNA changes in CBMC progenitor and non-progenitor subpopulations.

<p>(A) Sanger sequencing of <i>WT1</i>-cDNA in subpopulations of cb44 shows that G-to-A alteration at c.1303 is grossly higher in non-progenitor as compared to progenitor subpopulation. G-to-A alteration at both c.1303 (B) and c.1586 (C) were also found to be higher in the non-progenitor subpopulation of cb47 sample, as compared to the progenitor one. (D) Sequencing of the <i>WT1</i>-cDNA clones in cb47 subpopulations confirms the differential changes at c.1303 and c.1586, and also shows a minor T-to-C change at c.1368 which is significantly higher in non-progenitor as compared to the progenitor subpopulation. ** <i>P</i> < 0.01. *** <i>P</i> < 0.001.</p

Association of mRNA changes with canonical <i>WT1</i> variants.

<p>(A) Sanger sequencing of the <i>WT1</i> cDNA clones shows that all classic c.1618A>G alterations are in <i>cis</i> with canonical-KTS isoforms. (B) All alternative c.1586G>A mRNA changes are in <i>cis</i> with functionally relevant +KTS variants. *** <i>P</i> < 0.001.</p

Screen of candidate genes by the ability of targeted siRNAs to reverse c.1303G>A alteration in CBMC samples.

<p>(A) Six selected genes were screened by specific siRNAs, and the resultant A% values at c.1303 were calculated from the <i>WT1</i> cDNA clones sequenced. A3A-si1 resulted in nearly complete reversal of c.1303G>A change, with no evidence of G-to-A alterations elsewhere. Values indicate the mean +/- SEM. (B) Silencing efficiencies of different <i>A3A</i>-siRNAs were assessed by Taqman gene expression assay in CBMCs. (C) Phenotypic analysis of corresponding <i>A3A-</i>silenced CBMCs using Sanger sequencing of the <i>WT1</i>-cDNA shows a virtually complete reversal of c.1303G>A change by A3A-si1 and A3A-si2, and a partial reversal by A3A-si3. (D) Quantification of the results in (C) above, as determined by Sanger sequencing of the <i>WT1</i>-cDNA clones, confirming qualitative data. *** <i>P</i> < 0.001.</p

Differential expression of <i>A3A</i> mRNA in progenitor as compared to non-progenitor CBMCs.

<p>(A) Six CBMC samples were sorted into progenitor and non-progenitor cells, and <i>A3A</i> mRNA expression was assessed and normalized to <i>GAPDH</i> mRNA level. <i>A3A</i> expression in six pairs of samples was on average 228 (SD = 298) fold higher in non-progenitors as compared to progenitors, corresponding to differential G-to-A editing in these populations. (B) Three pairs of pooled CBMC samples were sorted into progenitor and non-progenitor subpopulations and examined for A3A level, showing higher levels in non-progenitors. (C) Quantitation of the A3A Western blot bands normalized to beta-Actin, confirming higher A3A levels in non-progenitor cells.</p

DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues

Mouse CD8 alpha(+) dendritic cells (DCs) in lymphoid organs and CD103(+) CD11b(-) DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8 alpha(+) DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8 alpha(+) DC has recently b een questioned. Furthermore, the identification of "CD8 alpha(+) DC-like" cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage members. Here we show that mouse CD8 alpha(+) DCs and CD103(+) CD11b(-) DCs can be defined by shared high expression of DNGR-1 (CLEC9A). We further show that DNGR-1 uniquely marks a CD11b(-) human DC population present in both lymphoid and nonlymphoid tissues of humans and humanized mice. Finally, we demonstrate that knockdown of Batf3 selectively prevents the development of DNGR-1(+) human DCs in vitro. Thus, high expression of DNGR-1 specifically and universally identifies a unique DC subset in mouse and humans. Evolutionarily conserved Batf3 dependence justifies classification of DNGR-1(hi) DCs as a distinct DC lineage. (Blood. 2012; 119(25): 6052-6062