Abstract:
:Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression.
journal_name
Bloodjournal_title
Bloodauthors
Josefsdottir KS,Baldridge MT,Kadmon CS,King KYdoi
10.1182/blood-2016-03-708594subject
Has Abstractpub_date
2017-02-09 00:00:00pages
729-739issue
6eissn
0006-4971issn
1528-0020pii
blood-2016-03-708594journal_volume
129pub_type
杂志文章相关文献
BLOOD文献大全abstract::We report a novel chromosome translocation--t(2;5)(p23;q35) or its variant, t(2;5;13)(p23;q35;q12)--in 3 patients with peripheral T-cell lymphoma. All 3 were female children who had peripheral lymphadenopathy without organomegaly and underwent complete remission with or without chemotherapy. Their tumors were characte...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-02-15 00:00:00
abstract::We evaluated phagocytic and lytic activities of peripheral blood monocytes (PBMo) from patients with thalassemia major (ThP) using C pseudotropicalis as the target. PBMo from ThP showed decreased lytic activity (P less than .001), whereas the phagocytic activity did not differ from that of the controls. Significant in...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Expression of the von Willebrand factor (vWF) gene is restricted to the endothelial and megakaryocyte lineages. Within the endothelium, expression of vWF varies between different vascular beds. We have previously shown that the human vWF promoter spanning a region between -2182 (relative to the start site of transcrip...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-11-15 00:00:00
abstract::Large granular lymphocyte (LGL) leukemia results from clonal expansion of CD3+ cytotoxic T lymphocytes or CD3- natural killer (NK) cells. Chronic antigen stimulation is postulated to promote long-term survival of LGL leukemia cells through constitutive activation of multiple survival pathways, resulting in global dysr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-09-808816
更新日期:2018-06-21 00:00:00
abstract::During acute falciparum malaria infection, red blood cells (RBC) containing abundant ring-infected erythrocyte surface antigen (Pf 155 or RESA), but no intracellular parasites, are present in the circulation. These RESA-positive parasite negative RBC are not seen in parasite cultures in vitro. This indicates that in a...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::In this issue of Blood, Goussetis et al identify autophagy as a new pathway for the degradation of the oncoprotein BCR-ABL. They show that the therapeutic drug arsenic trioxide (AS(2)O(3)) targets BCR-ABL for autophagic degradation via a p62/SQSTM1-dependent mechanism that is critical for the antileukemic effect of th...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2012-08-451492
更新日期:2012-10-25 00:00:00
abstract::The deregulated Bcr/Abl tyrosine kinase is responsible for the development of Philadelphia (Ph)-positive leukemia in humans. To investigate the significance of the C-terminal Abl actin-binding domain within Bcr/Abl p190 in the development of leukemia/lymphoma in vivo, mutant p190 DNA constructs were used to generate t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::We performed a longitudinal analysis of point mutations of the N-ras proto-oncogene in patients with myelodysplasia and a follow-up of at least 2.5 years after diagnosis. Point mutations at codons 12, 13, and 61 of the N-ras oncogene were analyzed after in vitro amplification of N-ras specific sequences followed by do...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an elevation in the serum viscosity do not require plasma exchange, and the majority will have other indications for therapeutic intervention. For patients w...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2018-06-846816
更新日期:2018-09-27 00:00:00
abstract::Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 t...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2016-11-750612
更新日期:2017-10-05 00:00:00
abstract::The t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in up-regulation of cyclin D1. We used a segregation fluorescence in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to qu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-11-3837
更新日期:2004-08-15 00:00:00
abstract::Although small deletions, splice site abnormalities, missense, and nonsense mutations have been identified in patients with factor VII deficiency, there have been no reports of mutations in the factor VII promoter. We investigated a girl with factor VII levels that were less than 1% of normal in association with a sev...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Digital protein assays have great potential to advance immunodiagnostics because of their single-molecule sensitivity, high precision, and robust measurements. However, translating digital protein assays to acute clinical care has been challenging because it requires their deployment with a rapid turnaround. Herein, w...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019004399
更新日期:2020-12-04 00:00:00
abstract::Subsets of natural killer (NK) cells are characterized by the expression of inhibitory and/or stimulatory receptors specific for major histocompatibility complex (MHC) class I determinants. In mice, these include the Ly49 family of molecules. One mechanism by which tumor cells may evade NK cell killing is by expressin...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.10.3132
更新日期:2001-05-15 00:00:00
abstract::The peripheral blood lymphocyte surface markers and clinical features of 38 patients with common variable immunodeficiency (CVID) were assessed. These studies identified a subset of CVID consisting of 14 of the 38 patients with a distinctive T-cell immunophenotype and clinical findings. The phenotypic changes were cha...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-11-15 00:00:00
abstract::Factor XIII is the fibrin-stabilizing factor that covalently cross-links fibrin monomers to form a highly organized, stable fibrin clot. The plasma form of factor XIII is a heterodimer, a2b2, consisting of two a-chains and two b-chains; the intracellular form, such as in platelets and placenta, is a dimer, a2, consist...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::The origin of low-grade mucosa-associated lymphoid tissue (MALT)-type B-cell lymphoma is still unclear. Using a novel two-step procedure, we have sequenced the Ig VH genes expressed by cells from four patients with gastric low-grade MALT-type lymphoma. The nucleotide sequences of the complementarity determining region...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::In this issue of Blood, White et al provide compelling evidence that the intrinsic apoptotic caspase cascade, while required for megakaryocyte and platelet death under pathophysiologic conditions, is dispensable for normal platelet formation and function. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2012-02-410423
更新日期:2012-05-03 00:00:00
abstract::Our previous study demonstrated that 2-methoxyestradiol (2ME2), an estrogen derivative, induces apoptosis in multiple myeloma (MM) cells; however, the related transcriptional events are unclear. In the present study, we used oligonucleotide microarrays to identify genes altered during 2ME2-induced apoptosis in MM cell...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-10-3146
更新日期:2003-05-01 00:00:00
abstract::In human follicular lymphoma the t(14; 18) chromosome translocation activates the antiapoptotic oncogene Bcl2 by linking it to the immunoglobulin heavy chain (IGH) locus. Transgenic mice expressing Bcl2 controlled by an Igh enhancer (E mu) do not develop follicular lymphoma, although they do have an increased incidenc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2469
更新日期:2004-03-15 00:00:00
abstract::Transfusions purportedly induce dysfunction of cell-mediated immunity in sickle cell anemia (SCA). We studied hematologic and lymphocytic indices in 173 human immunodeficiency virus (HIV)-negative subjects with SCA and 131 black controls. Children aged 1 to 7 years with SCA had leukocyte counts and percentages of gran...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-04-15 00:00:00
abstract::This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n=252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-09-046144
更新日期:2007-06-15 00:00:00
abstract::Nomifensine (Merital, Alival; Hoechst, Frankfurt, FRG), an antidepressant drug, may cause immune hemolytic anemia (IHA) of the so-called immune complex type that is believed to occur by means of an innocent-bystander mechanism. In this report we describe findings that are not consistent with this mechanism in a patien...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model. We now tested whether endogenous platelet PF4 content affects APC generation. Mice completely deficient in PF4 (mPF4(-/-)) had impaired AP...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-03-081901
更新日期:2007-09-15 00:00:00
abstract::Recently, we have identified scavenger receptor class A member I (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of an FX reservoir at the macrophage surface. Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2 (PTX2). The presence of PTX2 is essential to ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-06-724351
更新日期:2017-04-27 00:00:00
abstract::Human hematopoietic stem cells are pluripotent, ie, capable of producing both lymphoid and myeloid progeny, and are therefore used for transplantation and gene therapy. An in vitro culture system was developed to study the multi-lineage developmental potential of a candidate human hematopoietic stem cell population, C...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4+ T-ce...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2016-06-718619
更新日期:2016-10-27 00:00:00