摘要:

Abstract:HL60 cells were cultured for 10 days under various experimental conditions. They were then incubated with 1 μmol/l [5‐3H] uridine for 2 hours and their DNA extracted. The DNA was hydrolysed to deoxyribonucleosides with phosphodiesterase and alkaline phosphatase and the hydrolysate subjected to Aminex A6 chromatography. The elution profiles showed that, when compared with control cells, DNA from cells grown in medium deficient in folate, B12or both folate and B12contained increased amounts of deoxyuridine (dU) and increased radioactivity in the dU peak. The data demonstrate that misincorporation of uracil into DNA occurs in a myeloid cell line cultured in growth medium deficient in folate, B12or both folate and B

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00080.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:To evaluate the effect of IL‐4 on the growth of leukemic cells from adult T‐cell leukemia (ATL) patients (ATL cells) and determine whether the IL‐4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL‐4in vitro.Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL‐2 and IL‐4 in a dose‐dependent manner. The proliferative response to IL‐4 was higher than that obtained with IL‐2 in 8 patients. The expression of the IL‐2 receptor (IL‐2R) αα‐chain in leukemic cells from some patients was also enhanced by IL‐4. The IL‐4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL‐4‐induced proliferation of ATL cells nor IL‐4‐induced IL‐2R expression on ATL cells was inhibited by anti‐Tac or anti‐IL‐2 antibody and, therefore, these effects of IL‐4 are considered independent of endogenous IL‐2 activity. However, IL‐2 and IL‐4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme‐linked immunosorbent assay. Interferon‐γ (IFN‐γ) partially inhibited IL‐2‐ or IL‐4‐induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL‐2 or IL‐4 paracrine mechanism in lymphoid tissuein viv

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00081.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Reverse transcriptase‐polymerase chain reaction amplification (RT‐PCR) and Southern blot analysis were used to evaluate ligand and receptor expression of interleukin 1α (IL‐1α), interleukin 3 (IL‐3), interleukin 6 (IL‐6) and stem cell factor (SCF) in peripheral blood lymphocytes and monocytes and in several acute leukemia blast cell populations. Resting peripheral lymphocytes and monocytes expressed both ligand and receptor of the four cytokines at considerable levels. The leukemic blast cells of the M1‐M4 phenotypes are characterized by almost complete lack of expression of IL‐1α, IL‐3 and IL‐6 and the constant and usually high expression of SCF. On the other hand, these myeloid blast cells express generally high levels of the four cytokine receptors. The data suggest that the regulation of the expression of IL‐1α, IL‐3 and IL‐6, at least in our limited number of leukemic cell populations studied, is independent of that of SCF. The results indicate that, at least in most of the leukemic myeloid blasts cells, the expression of SCF and its receptor, the c‐kit oncogene, may permit an autocri

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00082.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Plasma and cellular pharmacokinetics of m‐AMSA were investigated in 5 patients with acute leukemia, using HPLC. The pharmacokinetic data served as a guideline forin vitrotoxicity tests on clonogenic bone marrow cells. m‐AMSA was administered as a 3‐hour intravenous infusion of 100 mg/m2. Median plasma and nucleated blood cell peak concentrations were 1.25 and 6.36 μg/ml followed by biphasic elimination with a median T1/2αα of 1.6 h and 0.3 h and a median T1/2β of 5.0 h and 5.0 h respectively. Median plasma and cellular area under the curve (AUC) for a 24‐h period amounted 6.2 μug·h/ml and 49.8 μg·h/ml respectively.In vitrocellular uptake was maximal at least within 30 minutes. No differential toxicity for CFU‐GM and CFU‐L was observed in relation to exposure time. Median IC50for CFU‐GM and CFU‐L was 2.2, 1.8 and 1.6 μg/ml after incubation periods of resp. 0.08, 4 and 24 h. The corresponding m‐AMSA concentration × time products to achieve 50% inhibition (IAUC50) were 0.18, 7.2 and 38.4 μg·h/ml, respectively. 48‐h prestimulation of the clonogenic bone marrow cells with Human Placenta Conditioned Medium increased sensitivity (median 1.7 ×) after 4 h incubation with mAMSA. Short exposure provides maximal, concentration‐related, cellular uptake, resulting in effective inhibition of grow

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00083.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:We performed immunocytochemical detection of myeloperoxidase (MPO), using monoclonal antibody MPO‐7, in 15 consecutive cases of adult acute leukemia (AL) unclassified by conventional cytological and cytochemical criteria and 7 AML‐M, with less than 10% of cytochemically MPO‐positive blasts. In AL with negative MPO cytochemistry the anti‐MPO reaction was positive in 5 of the 15 patients with 3, 3, 7, 11 and 45% positive blasts respectively. In AML‐M1, immunocytochemistry was positive in a larger percentage of blasts than cytochemistry in 2 cases. Immunological detection of myeloid surface markers was positive in all 15 cases of unclassified AL (including the 10 AL with negative anti‐MPO reaction). Eleven of the 22 patients from this study had mixed lymphoid‐myeloid phenotype. Discrepancy between immunological MPO detection and light cytochemistry was more frequent in patients with mixed immunophenotype than in patients without lymphoid markers. No relationship between MPO‐antigen positivity and clinical or biological features was seen. These findings confirm immunological detection of MPO as useful for the diagnosis of poorly differentiated AL. The high incidence of inactive MPO detectable only by immunocytochemistry in mixed lineage AL needs

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00084.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The incidence and mortality of bleeding complications have been investigated in 438 patients with acute leukaemia consolidated either by chemotherapy (n = 241) or by bone marrow transplantation (n = 197). Bleeding signs on admission were found in 38% of the chemotherapy‐treated group. Haemorrhagic deaths during the 1st month were seen in 10%. The majority of the major bleedings were localized intracranial, but gastrointestinal haemorrhages were also common. The platelet count was significantly lower (40 × 109/1 versus 69 × 109/1, p<0.001) and the leukocyte count significantly higher (31.2 × 109/1 versus 11.6 × 109/1, p<0.001)in the group with bleeding complications than in those without. The haemorrhagic mortality in patients consolidated with chemotherapy compared with transplant patients was similar, 23% and 19%. The majority of the lethal haemorrhages in the latter group were observed in patients undergoing allogenic bone marrow transplantation after engraftment. Septicaemia, graft‐versus‐host and venous occlusive disease were contributin

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00085.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normaldonormicein vivowith GM‐CSF. Donor balb/c mice were injected i.p. with GM‐CSF (5000 u) or saline. Seventy‐two hours later 5 × 105BM cells from either GM‐CSF‐treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM‐CSF‐treated donors, significantly higher CFU‐S and significantly higher survival rate (57% [n = 65];vs.30% [n = 63]; p<0.05) were noted. Donor mice of the GM‐CSF group did not differ in bone‐marrow cellularity and composition from their controls. However, recipients of BM from GM‐CSF‐treated mice had higher blood counts of haemoglobin, leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM‐CSF may be of benefit in improving surviva

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00086.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Recent attempts to reduce 3′azido‐3′deoxythymidine (AZT)‐induced anemia in AIDS patients have focused both on AZT dose reduction and on the use of recombinant cytokines. The newly cloned cytokine stem cell factor (SCF) is a potent regulator of hematopoietic progenitor cell proliferation. Therefore, we attempted to ameliorate AZT‐induced anemia using stem cell factor (SCF) in the LP‐BM5 murine leukemia virus‐induced model of AIDS (MAIDS). SCF was administered with oral AZT for up to 1 month, and effects on erythropoiesis examined. SCF alone increased both splenic BFU‐E and CFU‐E. AZT alone also increased the number of splenic BFU‐E and CFU‐E. SCF, administered to AZT‐treated MAIDS mice, did not further enhance these increases. SCF increased bone marrow cellularity in AZT‐treated MAIDS mice. However, the total number of bone marrow BFU‐E was unaffected. In contrast, AZT, SCF, and the combination significantly decreased bone marrow CFU‐E. SCF alone increased the absolute numbers of peripheral blood reticulocytes in MAIDS mice, but did not increase reticulocyte numbers in AZT‐treated mice. SCF did not significantly increase hematocrits in either control or AZT‐treated mice. Further studies are needed to maximize the differentiating capacity of the enlarged erythroid pr

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00087.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00088.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00089.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY