3 research outputs found
Temperature and Field Dependence of Magnetization Measured on a Grain Aligned Hg-1223 Samples
No full textOutcomes of Cessation of Nucleos(t)ide Analog Administration on Hepatitis B Virus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation : A Nationwide Retrospective Study
No full textMonitoring of hepatitis B virus (HBV)-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogs (NAs) are recommended to prevent the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the effect of NA cessation on the recurrence of HBV reactivation. This study aimed to clarify the consequences of NA cessation in allo-HSCT recipients with resolved HBV infection who experienced HBV reactivation following transplantation. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed with HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT between January 2010 and December 2020. A total of 72 patients from 16 institutions were registered (median age, 60 years; age range, 27 to 73 years; 42 males and 30 females). The day of initial HBV reactivation ranged from day 10 to day 3034 after allo-HSCT (median, 513 days). Anti-HBs were lost in >80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs, and no fatal HBV reactivation -related hepatitis was observed. HBV-DNA without hepatitis was continuously detected in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 of 72 patients (33%) by physician decision. Second HBV reactivation occurred in 11 of the 24 patients (46%) in whom administration of NAs was discontinued. The duration of NA treatment did not differ signi ficantly between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with an anti-HBs titer of >10 mIU/mL at the time of NA cessation. Multiple reactivations of HBV after NA cessation was common in patients with HBV reactivation who underwent alloHSCT despite the long duration of NAs. Careful monitoring of HBV-DNA is important even after the discontinuation of NAs in the case with HBV reactivation after allo-HSCT, because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs
FOG-1, a transcriptional regulator within the haematopoietic system
No full textFriend of GATA-1 (FOG-1) is a member of the friend of GATA (FOG)
family of proteins, which consists of large multitype zinc finger cofactors that
bind to the amino zinc finger of GATA transcription factors and modulate their
activity. FOG-1 also interacts with the C-terminal binding protein (CtBP),
mainly known as a corepressor and the nucleosome remodelling and histone
deacetylase repressive (NuRD) complex ; thus, integrating FOG-1 into the
transcription factor and chromatin modifier networks. Remarkably, the protein
activates or represses gene transcription by facilitating binding of GATA
factors to DNA, recruiting chromatin remodelling complexes, or by stabilizing
tissue-specific chromatin loops. Physical interaction between FOG and GATA
proteins in vivo is essential for the development of a broad array of tissues,
reflecting the overlapping expression patterns of these factors. Notably, within
the haematopoietic system, FOG-1 is absent in most of the myeloid lineages ;
it is expressed at high level in multipotent progenitors, erythroid and
megakaryocytic cells, low level in lymphoid and haematopoietic stem cells.
The cofactor is essential for differentiation of the erythroid and
megakaryocytic lineages, notably by interacting with GATA-1. FOG-1 also
plays a role in the T-lineage by repressing GATA-3 dependent induction of
Th2 development. Interestingly, overexpression of FOG-1 in avian
eosinophils, which do not normally express FOG-1, reprograms these
differentiated cells into multipotent cells. To study FOG-1 in mammals, we
used a novel transgenic mouse model strategy which we had designed to
generate mice with conditional overexpression of FOG-1. Our work with
enforced expression of FOG-1 in the whole murine haematopoietic system led
to a reduction in the number of circulating eosinophils, confirming and
extending to mammals the previously reported role of FOG-1 in repressing
this lineage development. Strikingly, we have identified the expression of
FOG-1 in early B lymphocytes, but not in late developmental stages such as
mature B cells and plasma cells. Moreover, FOG-1 function had never been
described in the B-lineage, where GATA factors are not expressed. Therefore,
we were intrigued by both the regulated expression of FOG-1 during B cell
development and its molecular mechanism of action in the absence of GATA
factors. Thus, we generated transgenic mice in which FOG-1 expression was
enforced at a physiologically relevant level in the B lymphoid system : in
mature B cells and from early B cell stages. We found that sustained FOG-1
expression in mature and late B cells did not affect their development or
function, contrary to our expected hypothesis. Although the mice
overexpressing FOG-1 from early B cell lineages showed only a weak
phenotype, we extensively studied FOG-1 partners in early B cell stages.
Indeed, describing FOG-1 molecular mechanism of action in the absence of
GATA factors is a question that warrant further investigation. We notably
found FOG-1 in complex with Ikaros, a transcription factor well described as
crucial for B cell development. The cofactor was also found associated to the
CtBP and NuRD epigenetic complexes in B cell lines
