4 research outputs found

    Complex interactions among tissue restricted transcription factors and cofactors are critical for intestine specific gene expression

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    As might be concluded from the general introduction about gene regulation, our understanding of how transcription factors regulate transcription ofLPH and SI is extensive. Both LPH and SI are enterocyte specific membrane anchored enzymes that are necessary for the digestion of nutrients present in the specific diets of mammals according to their age before and after weaning. Previous work by Grand et. al. has demonstrated that LPH and SI are expressed in complex patterns along the vertical, horizontal, and developmental gradient of the small intestine. LPH and SI expression patterns coincide with important transitions during small intestine development. Furthermore, Krasinski et. al. demonstrated that specific regions in the LPH promoter contain the information necessary for the specific patterns of expression. Krasinski et. al also demonstrated that the vertical, horizontal, and developmental LPH and SI expression patterns are regulated at the level of transcription. Therefore, LPH and SI genes are perfect markers for cell differentiation of small intestine. Seqeunce analysis of the 5 '-flanking regions ofLPH and SI genes revealed consensus binding sites for Cdx-2, HNF-1, and GATA transcription factors. The families of these transcription factors have all been indicated to play a role in cell differentiation and morphogenesis. These transcription factors are turned on in early stages of intestinal development, are only expressed together in the small intestine, and their binding sites are in close proximity to each other and the TAT A-box regions suggesting that they play an important role in cell differentiation and intestine specific gene regulation. The close proximity of these binding sites to each other and the fact that these transcription factors have been shown individually to cooperate with comparable proteins for the regulation of gene expression, it is hypothesized that these factors act in concert to regulate LPH and SI transcriptio

    Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: Implications for monitoring of minimal residual disease

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    We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) and 600 blood samples] by use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10 and CD19. Additionally, 60 BM follow-up samples from six patients were subjected to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions of normal precursor B cells in regenerating BM not only after maintenance therapy but also during treatment. At the end of the 2-week intervals after consolidation and reinduction treatment, B-cell-lineage regeneration was observed in BM with a large fraction of immature CD34+/TdT+ B cells. In contrast, in regenerating BM after cessation of maintenance treatment, the more mature CD19+/CD10+ B cells were significantly increased, but the fraction of immature CD34+/TdT+ B cells

    Response to Vaccination in Infants Exposed to Antitumor Necrosis Factor Alpha In Utero

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    In this retrospective cohort study, the response to routinely administered Haemophilus influenzae type B vaccine, pneumococcal and pertussis vaccinations in 27 children exposed to antitumor necrosis factor alpha (anti-TNF alpha) during pregnancy was measured. The overall vaccination response seems comparable for children exposed to anti-TNF alpha and healthy infants. After primary vaccination series, inadequate response was present in some patients and might be related to exposure to anti-TNF alpha
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