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Abstract 1492 Poster Board I-515 Previous studies have established an important role for reactive oxygen species (ROS) in regulating the function and life-span of hematopoietic stem cells (HSC). Nuclear factor erythroid-2–related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates cellular responses to ROS and detoxification pathways implicated in chemoresistance, however, its role in normal stem cells is unknown. We analyzed Nrf2null mice and found increased total bone marrow cellularity, cKit+Sca1+Lin− (KSL) stem-progenitor cells, and long-term quiescent HSC (CD34−KSL) compared to wild type mice (p Disclosures: No relevant conflicts of interest to declare.

Background: There is a growing consensus about the validity of human personality traits as important dispositions toward feelings and behaviors (Matthews, Deary,& Whiteman, 2003). Materials and Methods: Here we examine the reliability of the Hindi translation of the Eysenck Personality Questionnaire-Revised Short Form (EPQR-S; Eysenck, Eysenck,& Barrett, 1985), which consists of 48 items that assess neuroticism, extraversion, psychoticism, and lying. The questionnaire was first translated into Hindi and then back translated. Subsequently, it was administered to 202 students (78 men and 124 women) from Banaras Hindu University. The internal consistency of the scale was evaluated. Results: The findings provide satisfactory psychometric properties of the extraversion, neuroticism and lie scales. The psychoticism scale, however, was found to be less satisfactory. Conclusion: It can be proposed that due to satisfactory internal consistency scores, the EPQRS-H is a reliable scale for the measurement of various personality traits.

Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma is one of the common T cell lymphomas in Western countries. Many patients present with symptoms of a systemic disease and diagnosis can often be challenging. Particularly in cases in which histological confirmation cannot be easily achieved flowcytometry of peripheral blood can give important clues for the differential diagnosis of AILD. We have previously reported that CD4-negative CD3+ T-cells in peripheral blood are a characteristic immunophenotypic finding in AILD patients. Gene scan analysis for the TCR gamma chain and intracellular CD3 expression clearly showed that these CD3-negative CD4+ cells are of T cell origin. In this study we further evaluated the phenotype of the CD4− CD3+ T cells and we compared their frequency in AILD patients with the frequency in patients with other histologically confirmed leukemic T cell lymphomas. 14 patients with AILD (clinical stage III/IV) were compared with 26 patients with other subtypes of leukemic T cell lymphomas (6 T-large granular lymphocyte leukemias (T-LGL), 4 T-chronic lymphocytic leukemias/prolymphocytic leukemias (T-CLL/PLL), 5 anaplastic large cell lymphomas (ALCL), 1 adult T-cell leukemia/lymphoma (ATLL), 1 mycosis fungoides and 9 peripheral T-cell lymphomas. Flowcytometric analysis of peripheral blood was performed in a lymphocyte gate using fluorochrome-labeled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD16, CD56, CD57 and TCR. In 14/14 AILD patients a small but distinct population of CD3-negative CD4+ T cells was found (mean percentage of CD3-negative CD4+ T cells in the gate: 12,0 ± 17,6 %, range 0,05 – 51,8 %). In contrast, CD3-negative CD4+ T cells could be detected in only 1/26 patients with other leukemic T cell lymphomas. This patient had been diagnosed with mycosis fungoides. Further immunophenotypic analysis showed that the aberrant T cells in AILD also express pan T cell markers, such as CD2, CD5 and partially CD7, surface TCR expression could not be detected. In conclusion our comparative study shows that flowcytometric detection of CD3-negative CD4+ T cells in peripheral blood is a characteristic feature of AILD with a high specificity. Therefore, flowcytometry is particulary useful in the differential diagnosis of AILD, even if the aberrant T cell population has a very low frequency. Although AILD is mostly CD3+ on immunohistochemistry, the presence of low numbers of CD3-negative CD4+ T cells in peripheral blood appears to be a typical feature of AILD. Cytoplasmic CD3-expression is one possible explanation for this discrepancy. Since complete or partial loss of pan T cell antigens is a characteristic feature of many T cell lymphomas, the aberrant CD3-negative CD4+ T cells might also represent just a subfraction of lymphoma cells in AILD. Further biological characterization of this subpopulation should be performed.

Structural polymorphism of DNA has constantly been evolving from the time of illustration of the double helical model of DNA by Watson and Crick. A variety of non-canonical DNA structures have constantly been documented across the globe. DNA attracted worldwide attention as a carrier of genetic information. In addition to the classical Watson–Crick duplex, DNA can actually adopt diverse structures during its active participation in cellular processes like replication, transcription, recombination and repair. Structures like hairpin, cruciform, triplex, G-triplex, quadruplex, i-motif and other alternative non-canonical DNA structures have been studied at length and have also shown their in vivo occurrence. This review mainly focuses on non-canonical structures adopted by DNA oligonucleotides which have certain prerequisites for their formation in terms of sequence, its length, number and orientation of strands along with varied solution conditions. This conformational polymorphism of DNA might be the basis of different functional properties of a specific set of DNA sequences, further giving some insights for various extremely complicated biological phenomena. Many of these structures have already shown their linkages with diseases like cancer and genetic disorders, hence making them an extremely striking target for structure-specific drug designing and therapeutic applications., Graphical abstract fx1, Highlights • DNA can adopt diverse range of structures other than classical Watson–Crick duplex. • Discussion of alternate structures like hairpin, cruciform, triplex, quadruplex etc. • This review gives some insights for the biological relevance of DNA structures.

Introduction Cut throat injuries are well recognized in homicide but less recognized in suicides. The incidence of suicide is increasing worldwide owing to the more stressful strenuous lifestyle and other risk factors like substance abuse. Suicide by incising one’s own throat is associated with hesitation marks whereas homicidal wounds are not. Case Report We present an interesting case of a suicidal cut throat of the victim being a butcher who was on alcohol abstinence since 3 days with severe injuries of supraglottic larynx and cricopharynx, surprisingly without any evidence of hesitation marks. He underwent immediate neck exploration and suturing of the injured structures without the need of a tracheostomy. Discussion A multidisciplinary approach by Otolaryngologists, Psychiatrists, Intensivists, and Anaesthetists is required in the effective management of these victims. A thorough proper early assessment can totally avoid the need of tracheostomy which is recommended in practice, hence preventing complications arising out of this unnecessary but advocated procedure.

The E3 ubiquitin ligase Cbl-b is a negative regulator of TCR signaling that: 1) sets the activation threshold for T cells; 2) is induced in anergic T cells; and 3) protects against autoimmunity. However, the role of Cbl-b in regulating CD8 T cell activation and functions during physiological T cell responses has not been systematically examined. Using the lymphocytic choriomeningitis virus infection model, we show that Cbl-b deficiency did not significantly affect the clonal expansion of virus-specific CD8 T cells. However, Cbl-b deficiency not only increased the steady-state cell surface expression levels of TCR and CD8 but also reduced Ag-induced down-modulation of cell surface TCR expression by effector CD8 T cells. Diminished Ag-stimulated TCR down-modulation and sustained Ag receptor signaling induced by Cbl-b deficiency markedly augmented IFN-γ production, which is known to require substantial TCR occupancy. By contrast, Cbl-b deficiency minimally affected cell-mediated cytotoxicity, which requires limited engagement of TCRs. Surprisingly, despite elevated expression of CD8 and reduced Ag-induced TCR down-modulation, the functional avidity of Cbl-b-deficient effector CD8 T cells was comparable to that of wild-type effectors. Collectively, these data not only show that Cbl-b-imposed constraint on TCR signaling has differential effects on various facets of CD8 T cell response but also suggest that Cbl-b might mitigate tissue injury induced by the overproduction of IFN-γ by CD8 T cells. These findings have implications in the development of therapies to bolster CD8 T cell function during viral infections or suppress T cell-mediated immunopathology.