Abstract:
:Reduced ferrochelatase activity in erythropoietic protoporphyria (EPP) causes the accumulation of protoporphyrin IX (PPIX) leading to acute cutaneous photosensitivity and liver injury. Many EPP patients also have a mild hypochromic, microcytic anemia and iron deficiency. Iron deficiency can lead to decreased PPIX accumulation in another erythropoietic porphyria, congenital erythropoietic porphyria (CEP). Expression of the iron regulatory peptide hepcidin is negatively regulated by the serine protease TMPRSS6. Hepcidin induction by siRNA-mediated inhibition of TMPRSS6 expression reduces iron availability and induces iron deficiency. To interrogate the therapeutic potential of iron deficiency to modify EPP, we treated an ethylnitrosourea-induced mouse model of EPP, Fech m1Pas , with a GalNAc-conjugated Tmprss6 siRNA and PPIX levels, anemia and iron parameters were monitored. The GalNAc-RNAi therapeutic reduces Tmprss6 expression and induces mild iron deficiency in Fech m1Pas animals. However, decreases in erythrocyte PPIX levels and liver PPIX accumulation were not seen. These results indicate short-term induction of iron deficiency, at least in a murine model of EPP, does not lead to decreased PPIX production.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Schmidt PJ,Hollowell ML,Fitzgerald K,Butler JS,Fleming MDdoi
10.1002/ajh.25743subject
Has Abstractpub_date
2020-05-01 00:00:00pages
492-496issue
5eissn
0361-8609issn
1096-8652journal_volume
95pub_type
杂志文章abstract::Corticosteroids are essential and one of the mainstays in the treatment of acute lymphoblastic leukemia (ALL). In vitro assays show that dexamethasone(DXM) is five to six times more cytotoxic to leukemic lymphoblasts than prednisolone (PDN) [1], and the use of DXM as an alternative drug for PDN is an important issue i...
journal_title:American journal of hematology
pub_type: 信件,随机对照试验
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更新日期:2010-10-01 00:00:00
abstract::Thrombospondin (TSP), a large protein found in platelet alpha-granules (as TSP-1), mediates adhesion of sickle reticulocytes to cultured vascular endothelium. To further explore the physiologic relevance of this observation, we have measured plasma TSP levels and platelet TSP-1 content in subjects with sickle cell dis...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(SICI)1096-8652(199604)51:4<296::AID-AJH8>
更新日期:1996-04-01 00:00:00
abstract:OVERVIEW:Evidence suggests that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment r...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.23834
更新日期:2014-11-01 00:00:00
abstract::Extensive extralymphatic Hodgkin disease developed in a young man with common variable immunodeficiency manifested by hypogammaglobulinemia, recurrent sinopulmonary infections, and multiple autoimmune phenomena. Both humoral and cell-mediated immune dysfunction were present prior to treatment. After two cycles of chem...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830320212
更新日期:1989-10-01 00:00:00
abstract::The -117(G-->A)A gamma hereditary persistence of fetal hemoglobin (Greek HPFH) and beta zero 39-thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and beta zero 39...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830490402
更新日期:1995-08-01 00:00:00
abstract::The value of menorrhagia as a predictor for mild bleeding disorders has been very little studied and the results are divergent. In the present study on 30 women with objectively verified menorrhagia, we found a significantly increased prevalence of von Willebrand's disease (20%). By keeping a strict sampling and labor...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(SICI)1096-8652(199612)53:4<234::AID-AJH4>
更新日期:1996-12-01 00:00:00
abstract::We report here a patient with de novo acute myelocytic leukemia with trilineage myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal stage of the disease. Reverse transcription polymerse chain reaction (RT-PCTR)...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830490413
更新日期:1995-08-01 00:00:00
abstract::In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk Myelodysplastic Syndromes (MDS) patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytoge...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.25111
更新日期:2018-07-01 00:00:00
abstract::High-density lipoprotein (HDL) of 100-400 micrograms/ml did not prevent morphological alterations of human blood platelets treated with serotonin (1-5 microM). Highly concentrated HDL (1,200 micrograms/ml) appeared to activate platelets in vitro. These findings indicate that whole HDL may not inhibit agonist-induced p...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830500417
更新日期:1995-12-01 00:00:00
abstract::Leg ulcers are a well recognized complication of sickle cell disease that has been attributed to venous insufficiency. We studied 16 patients with sickle cell disease and active ulcers using venous pulse volume recordings and photoplethysmography (Doppler studies). Based on hemodynamic monitoring, all 16 patients exhi...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830370215
更新日期:1991-06-01 00:00:00
abstract::Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antige...
journal_title:American journal of hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/ajh.25780
更新日期:2020-06-01 00:00:00
abstract::We have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HM...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830350307
更新日期:1990-11-01 00:00:00
abstract::Therapies engineered to prolong clotting factor protein circulation time, manipulate the balance of pro-coagulant and anti-coagulant proteins, or introduce new genetic material to enable endogenous factor protein production dominate the clinical trial landscape of hemophilia. The availability of clotting factor concen...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.26018
更新日期:2021-01-01 00:00:00
abstract::We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one pati...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(SICI)1096-8652(199608)52:4<310::AID-AJH11
更新日期:1996-08-01 00:00:00
abstract::Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensiti...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830180202
更新日期:1985-02-01 00:00:00
abstract::Lysosomes (granules) of rabbit PMN leukocytes were extracted with either HCl or H2SO4, and the extracts were chromatographed over Sephadex to separate protein constituents. Some of the low molecular weight cationic proteins homogeneous on SDS PAGE (8% and 12.5% gels) were characterized by electrophoretic mobility in a...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830070309
更新日期:1979-01-01 00:00:00
abstract::A patient with acute nonlymphoblastic leukemia (FAB M4), showing a near tetraploid chromosome complement on his marrow cells, was treated with low dose cytosine arabinoside and achieved remission. During remission the near tetraploid marrow chromosome complement disappeared and reappeared upon relapse of leukemia. The...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830190412
更新日期:1985-08-01 00:00:00
abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 microg/m2) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3 1/2 times baseline by day 14. At day 5 marrow ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199801)57:1<7::aid-ajh2>3.
更新日期:1998-01-01 00:00:00
abstract::We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we de...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24223
更新日期:2016-02-01 00:00:00
abstract::Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the po...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24634
更新日期:2017-03-01 00:00:00
abstract::Transplant-associated thrombotic microangiopathy (TA-TMA) has a wide range of presentations after hematopoietic stem-cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA-TMA. Among the 1451 HSCT recipients, early TA-TMA occurred ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.25922
更新日期:2020-07-02 00:00:00
abstract:DISEASE OVERVIEW:The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic th...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.24102
更新日期:2015-09-01 00:00:00
abstract::We performed a laparoscopic splenectomy (LS) in 60 patients (age 9-83, 45 females) with idiopathic thrombocytopenic purpura (ITP) who did not achieve sustained remission on steroid therapy. Using a modified procedure, the mean duration of LS was 78 min (range 25-240 min) and surgery was associated with only 5% major a...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(200001)63:1<7::aid-ajh2>3.
更新日期:2000-01-01 00:00:00
abstract::The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order to establish its value ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.23672
更新日期:2014-05-01 00:00:00
abstract::Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majorit...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20147
更新日期:2004-09-01 00:00:00
abstract::This study investigated the clinical characteristics and prognostic relevance of CD34 expression in 47 patients with acute promyelocytic leukemia (APL), showing t(15;17) or PML/RARalpha. Ten (21.3%) of the APL patients were CD34(+). CD34 expression was associated with hypogranular morphology (P = 0.002) and hyperleuko...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10337
更新日期:2003-07-01 00:00:00
abstract::Sickle cell disease (SCD) is associated with early mortality. We sought to determine the incidence, cause, and risk factors for death in an adult population of patients with SCD. All patients aged >/=18 years seen at the Adult Sickle Cell Center at Duke University Medical Center between January 2000 and April 2005 wer...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21569
更新日期:2010-01-01 00:00:00
abstract::Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC)...
journal_title:American journal of hematology
pub_type: 杂志文章,多中心研究
doi:10.1002/ajh.25838
更新日期:2020-08-01 00:00:00
abstract::Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50-60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long-term prognosis. We r...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830330106
更新日期:1990-01-01 00:00:00
abstract::Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing gamma globin induction in response to a new ribonucleotide reductase inh...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830450208
更新日期:1994-02-01 00:00:00