Abstract:
:We developed a novel method for the chemical modification of cytokines with synthetic polymers to increase the therapeutic efficacy of the former in vivo. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for modification of interleukin-6 (IL-6) with polyethylene glycol (PEG). The novel PEG-conjugated IL-6 (DmPEG-IL-6), which had been pretreated with DMMAn before PEGylation, showed up to a 140% increase in in vitro specific activity compared with PEG-IL-6 that had been synthesized by the previous method. Moreover, DmPEG-IL-6 caused thrombopoiesis more potently in mice than PEG-IL-6. The DmPEG-IL-6 Fr.1, having 3-4 PEG chains attached to the cytokine, showed the strongest thrombopoietic effect among the DmPEG-IL-6s with different molecular sizes that were tested. PEG-IL-6 Fr.1 had a 500-fold higher potency in stimulating thrombopoiesis than native IL-6 and DmPEG-IL-6 Fr.1 achieved a threefold higher thrombopoietic effect than PEG-IL-6 Fr.1. In addition, side-effects, such as an increase in the plasma fibrinogen level, were not observed after injection of either PEG-IL-6s or DmPEG-IL-6s. These results suggest that PEGylation with DMMAn pretreatment may become a useful means for clinical cytokine delivery.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Tsunoda S,Ishikawa T,Watanabe M,Kamada H,Yamamoto Y,Tsutsumi Y,Hirano T,Mayumi Tdoi
10.1046/j.1365-2141.2001.02508.xsubject
Has Abstractpub_date
2001-01-01 00:00:00pages
181-8issue
1eissn
0007-1048issn
1365-2141pii
bjh2508journal_volume
112pub_type
杂志文章abstract::Human intravenous immunoglobulin (IVIg) and anti-D immunoglobulin preparations are used in the treatment of immune thrombocytopenic purpura (ITP). One mechanism proposed to explain their therapeutic effects in ITP patients is the induction of expression of anti-inflammatory cytokines, such as interleukin (IL)-10 or IL...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06495.x
更新日期:2007-03-01 00:00:00
abstract::The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Gro...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2141.1994.tb04827.x
更新日期:1994-04-01 00:00:00
abstract::This study aimed to assess the potential of human cord blood (CB) cells to engraft in the xenogenic non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model after in vitro expansion culture. We also studied the quality of human haemopoiesis arising from the transplantation of fresh or expanded cells i...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03254.x
更新日期:2002-01-01 00:00:00
abstract::Heparin binding on polymorphonuclear leucocytes (PMNL) was characterized. Heparin binding was specific, rapid, saturable and reversible. One single class of heparin binding sites was found with a dissociation constant of 1.22 mumol/l and 7.7 x 10(6) sites per PMNL. The binding was independent of the anticoagulant acti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08176.x
更新日期:1992-05-01 00:00:00
abstract::Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb02531.x
更新日期:1990-01-01 00:00:00
abstract::A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05391.x
更新日期:1995-12-01 00:00:00
abstract::We report the clinical presentation and the morphological, immunophenotypic, cytogenetic and molecular genetic characteristics of a 14 1/2-year-old boy who had French-American-British (FAB) type M1 acute non-lymphocytic (ANLL) leukaemia with a common T-ALL immunological phenotype, with no myeloid associated antigen, e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb03276.x
更新日期:1994-01-01 00:00:00
abstract::Smouldering multiple myeloma (SMM) presents without MM defining symptoms. We aimed to identify patients with SMM with an 80% risk of progression within 2 years using only serum parameters. In total, 527 patients with SMM were included and divided into a training group (287 patients from the Czech Myeloma Group [CMG]) ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16572
更新日期:2020-07-01 00:00:00
abstract::Hepatocyte growth factor (HGF) has been known as a versatile functional molecule, and as being involved in the colony formation of haemopoietic progenitor cells. Clinically, an elevated HGF level in the blood has been associated with liver diseases such as fulminant hepatic failure and acute hepatitis. We have found a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb08330.x
更新日期:1994-07-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis following first relapse. We present a subgroup analysis of an open-label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL. Oral lenalidomide 25 mg was self-administered...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2009.07626.x
更新日期:2009-05-01 00:00:00
abstract::Recent studies concerning the numbers of circulating clonal B cells in patients with multiple myeloma (MM) have reported conflicting data regarding the exact levels of clonal B cells and the existence of clonal cells in the CD34 compartment. In this report we show that high numbers of clonal cells with a phenotype of ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::We report a case of persistent infection with human parvovirus B19 (PVB19), manifesting clinically as recurrent agranulocytosis and in bone marrow biopsy as recurrent pure granulocytic aplasia. Persistence of parvovirus infection was documented by the presence of PVB19 DNA and anti-PVB19-IgM antibodies in the serum fo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08894.x
更新日期:1992-02-01 00:00:00
abstract::The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myel...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00962.x
更新日期:1998-10-01 00:00:00
abstract::The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. Thes...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb01879.x
更新日期:1976-01-01 00:00:00
abstract::Homing of transplanted bone marrow cells (BMC) to the host bone marrow (BM) is the first step of engraftment towards durable multilineage haematopoietic reconstitution. We used an in vivo assay to track PKH-labelled cells in the BM of mice after transplantation, using fluorescence microscopy through an optical window ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04114.x
更新日期:2003-02-01 00:00:00
abstract::When monocytic leukaemia line U937 cells were incubated in the presence of HgCl2 there was a rapid increase in tissue factor (TF)-dependent procoagulant activity, reaching a maximum (equivalent to the total TF activity observed when cells had been subjected to a freeze/thaw cycle) after 15 min at 50 microM HgCl2 and a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb04875.x
更新日期:1994-05-01 00:00:00
abstract::Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08431.x
更新日期:2011-06-01 00:00:00
abstract::Four patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with cyclosporine. The treatment with cyclosporine was based on the hypothesis that immune-mediated bone-marrow damage is the common pathogenetic mechanism of aplasia and PNH, with lack of GPI-linked ligands for an immune attack (i.e. LFA-3, CD...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1995.tb08907.x
更新日期:1995-01-01 00:00:00
abstract::We investigated the molecular basis of factor VII deficiency in a Japanese patient and identified a novel missense mutation in the signal sequence of the gene. Factor VII activity and antigen level measured in the patient were 10.7% and 11% of normal, respectively. All exons except 1B and the 5'-flanking region contai...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00666.x
更新日期:1998-04-01 00:00:00
abstract::Iron is required for monocyte/macrophage differentiation of HL-60 leukaemia cells. Differentiation requires induction of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1), and cell cycle arrest at the G1/S checkpoint. With iron depletion, p21 induction and differentiation are blocked. To establish the roles of iro...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03498.x
更新日期:2002-06-01 00:00:00
abstract::S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecula...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02218.x
更新日期:2000-09-01 00:00:00
abstract::Platelet and cell stimulation lead to plasma membrane remodelling, resulting in phosphatidylserine (PS) externalisation in the outer leaflet of the membrane, associated with the shedding of PS-rich microparticles (MPs), and contributes to thrombin generation by promoting the assembly of coagulation enzyme complexes. A...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05792.x
更新日期:2005-11-01 00:00:00
abstract::In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxo...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2141.2001.02526.x
更新日期:2001-02-01 00:00:00
abstract::Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 )...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17128
更新日期:2020-11-01 00:00:00
abstract::Diamond-Blackfan anaemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by red cell aplasia. Mutations in ribosomal genes are found in more than 50% of cases. Elevated erythrocyte adenosine deaminase (eADA) was first noted in DBA in 1983. In this study we determined the value of eADA for the ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12167
更新日期:2013-02-01 00:00:00
abstract::Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05646.x
更新日期:2005-08-01 00:00:00
abstract::Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotran...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04455.x
更新日期:2003-08-01 00:00:00
abstract::The level of venous thrombosis risk in women who experience spontaneous or induced pregnancy loss has previously been uncertain. However, recent data indicate that the risk of venous thrombosis in women undergoing pregnancy termination in the first trimester is increased two-fold compared to non-pregnant women but red...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16496
更新日期:2020-07-01 00:00:00
abstract::Marginal zone lymphoma represents about 10% of all non-Hodgkin lymphomas (NHLs). 33% of patients with acquired angioedema (AAE) due to acquired C1-inhibitor (C1-INH) deficiency (C1-INH-AAE) have or will develop NHLs. C1-INH-AAE is a rare condition. We report the follow-up of 72 C1-INH-AAE patients, followed for a medi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13908
更新日期:2016-03-01 00:00:00
abstract::In this paper we describe the placental transport of [3H]vitamin K1 in pregnant rats during the first 24 h after the oral administration of the vitamin. Vitamin K1 in the fetal livers ranged from 0.13% (3 h) to 2% (24 h) of the values found in the corresponding maternal livers. In spite of the low placental transfer o...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb06863.x
更新日期:1987-03-01 00:00:00