摘要:

Abstract: Megakaryocytes in fetal livers obtained from 30 water‐balloon aborted normal fetuses of 3 to 6 months' gestation, in the bone marrow from the same 30 fetuses, and another 9 fetuses of 7 to 8 months' gestation and in the normal bone marrow of adults were analyzed by immunocytochemical staining for size and maturation stage distribution and by flow cytometry for ploidy distribution simultaneously. In human fetuses, megakaryocytes showed a shift during ontogenesis from smaller towards larger size and from less mature towards a more mature stage with advancement of gestation. This was accompanied by a significant progressive shift to higher ploidy. However, the proportions (78.64%) of hypoploidy (≤8N) megakaryocytes in bone marrow of 7–8 months' gestation fetuses was still much higher than that (33.32%) in human adults (p<0.05), with the proportion of hyperploidy (≤16N) megakaryocytes lower than that (67.86%) in human adults. This result indicated that megakaryocyte polyploidization may be retarded or inhibited during de

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01349.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Recombinant cytokines such as stem cell factor (SCF) are currently being tested for the ability to ameliorate 3′azido‐3′deoxythymidine (AZT) induced anemia in AIDS patients. Recently, we demonstrated that SCF and heminin vitrogreatly increased the resistance of burst‐forming units erythroid (BFU‐E) to AZT. We therefore attempted to ameliorate AZT‐induced anemiain vivousing SCF and hemin in immunodeficient LP‐BM5 infected (MAIDS) mice. SCF and hemin were administered with oral AZT for 3 wk and the effects on erythropoiesis examined. Hemin significantly increased hematocrits of AZT‐treated mice and control mice. However, SCF and SCF–hemin combinations failed to raise hematocrits. Reticulocyte numbers were significantly consistently increased only in hemin‐treated mice receiving AZT. The numbers of CFU‐E were increased in bone marrow of AZT‐treated mice receiving hemin. Therefore, SCF did not enhance the erythropoietic effect of hemin in AZT‐t

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01350.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: It has been reported thatin vitroprednisolone (PDN) resistance provides a prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study aimed at investigating the biological and clinical significance ofin vitroPDN resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1 μm–35 μm) and cytotoxicity was determined by the soluble tetrazolium formazan 2,3‐bis (2‐methoxy‐4‐nitro‐5‐sulphophenyl)‐5‐[(phenylamino) carbamyl]‐2H‐tetrazolium hydroxyde (XTT) colorimetric assay. The IC50(defined as the drug concentration that results in 50% growth inhibition) varied greatly among the samples, from 0.3 μmto>35 μm; 15 μmwas subsequently chosen as IC50‐cut‐off point betweenin vitroresistant and sensitive cases. PDN‐induced cytotoxicity was significantly related to apoptosis, as demonstrated by regression analysis; in sensitive cases, however, the percentage of apoptotic cells afterin vitroPDN treatment was significantly increased compared with control (p=0.002). Immunofluorescence evaluation of intracellular BCL‐2 protein showed an equal percentage of positive cells in the two groups, but in resistant cells a higher mean fluorescence intensity (p=0.04) was demonstrated.In vitrosensitive and resistant patients did not display differences in clinical characteristics, in cytological, karyotypic and immunophenotypic features and in the outcome of induction therapy. Disease‐free survival (DFS), however, was significantly

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01351.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Results of studies using IFN‐α treatment for maintaining remission and prolonging survival in multiple myeloma (MM) are in conflict and trials seeking optimum use for this biological response modifier are continuing. Between 1989 and 1993 a prospective randomized multicentre trial was undertaken to evaluate the role of the combination of IFN‐α with chemotherapy (CT) in maintenance treatment of MM. For remission induction, in patients 65 yr or younger, we used VAD (group A) and for the remaining Melphalan and Prednisone (MP) (group B). For maintenance, patients were randomized to receive IFN‐α 3times106i.u. s.c. t.i.w. (group I) or alternating monthly cycles of IFN‐α and CT. The CT cycles were also alternated (VAD, MP, CP) in an effort to prevent the development of multidrug resistance. Median survival of the two maintenance groups from randomization (36 months for group I and 31 months for group II, p=0.3) as well as response duration (13 months in group I and 15 months in group II, p=0.95) were similar. Toxicities were more pronounced both with VAD induction and in the combination maintenance arm. The addition of chemotherapy to the IFN maintenance regimen in MM did not have an advantage o

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01352.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: The presence ofbcl‐2in myeloid leukemias has been associated with a decrease in therapy‐induced apoptosis, reduced patient survival andin vitroautonomous growth of leukemic cells. The present study focuses on the quantitation of resistance to increasing doses of 1‐β‐d‐arabinofuranosylcytosine (Ara‐C) by using hematological tumors expressing different levels ofbcl‐2.Scanning densitometry of Western blots demonstrated that the myeloid U‐937 cells express low levels ofbcl‐2(RD=0.008), whereas the follicular lymphoma RL‐7 expressed very high levels (RD=3.084). Colony formation was also examined following incubation with Ara‐C and RL‐7 cells demonstrated a higher clonogenic survival (LD50=0.5 μm) when compared with U‐937 cells (LD50=0.005 μm). Similarly, the level ofbcl‐2expression in each cell line was also related to apoptosis with U‐937 cells demonstrating increased DNA fragmentation when compared with RL‐7 cells. To further evaluate the effect of upregulatedbcl‐2on Ara‐C treatment, U‐937 cells were transfected with a retroviral vector carrying the murinebcl‐2or vector alone. Upregulation ofbcl‐2by myeloid leukemic cells increased the resistance by 3 logs to Ara‐C when comparing LD50values from clonogenic assays, and decreased apoptosis by at least 3 logs when

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01353.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Patients with severe iron overload may develop hepatic fibrosis due to iron toxicity. Unfortunately, the follow‐up of the fibrogenic activity during treatment by histological examination of tissue biopsies carries potential side effects, and may therefore not be justified ethically. Recently, the serum concentration of procollagen type III peptide (S‐PIIINP) has been shown to be a valid serum marker of the activity of collagen metabolism in conditions with hepatic fibrosis unrelated to iron overload. In order to evaluate the potential usefulness of this test in patients with fibrosis due to iron overload, we investigated the relationship between the PIIINP serum concentration and the size of iron overload in 18 patients with hereditary haemochromatosis (HH) and in 14 patients with transfusional iron overload. A close correlation was found between S‐ferritin and S‐PIIINP (r=0.73,p<0.0001). Follow‐up of 6 patients during iron depletion treatment revealed a normalization of the serum aminotransferase concentration before normalization of S‐PIIINP was found. This may indicate that excess iron directly induces an increase in fibrogenesis rather than the increased fibrogenesis is secondary to hepatocellular injury caused by iron excess. Thus, serial measurements S‐PIIINP may be useful in follow‐up of the fibrogenic process due

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01354.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Twenty‐one HIV negative Japanese patients with chronic hepatitis C who had congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9 million units 3 times a week of natural interferon (IFN)‐α for 6 months. They were followed, biochemically and virologically, for at least 18 months after therapy discontinuation to evaluate the long‐term results. Liver biopsy, hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase chain reaction (PCR) were performed to identify the predictors of a favorable response to IFN treatment. One male patient with hemophilia A dropped out because of general fatigue and was excluded from evaluation. Ten (50.0%) patients continued to be HCV RNA negative in serum together with normal ALT levels throughout the study. Subtype 1b and a high level of viremia significantly associated with an unfavorable outcome on the response to IFN although liver histology was not definitive for predicting the response. We concluded that a 6‐month treatment with high doses of natural IFN‐α was effective in inducing a long‐term response without relapse of viremia in 50% of chronic hepatitis C patients with congenital bleeding disorders and that HCV subtype and pretreatment level of viremia were useful predictors of the response to IFN in treatin

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01355.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: To test a hypothesis that interferon‐α (IFN) treatment might restore normal immunoglobulin (Ig) production in multiple myeloma (MM), the effect of IFN on Ig isotype (IgG and IgA) production by peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) in MM patients was analyzed by ELISA. IFN at a concentration of 1000 U/ml was found to enhance IgA production by PB MNCs in IgA‐MM and had a trend to stimulate IgG production in IgG‐MM. The effect of IFN on nonparaprotein Ig isotype production was more variable, with mostly neutral or inhibitory effects being seen in both the MM subtypes. In contrast to the influences observed in MM patients, IFN at the same concentration inhibited both IgG and IgA production by PB MNCs in healthy controls. In studying BM cells, IFN was found to reduce IgA production in IgA‐MM, but had a neutral effect on IgG production in IgG‐MM. In the controls, the production of both the IgG and the IgA isotypes by BM MNCs was decreased by IFN.On the basis of these results it seems that the disease itself somehow affects the Ig‐producing cells in MM, when measured as different responses of the cells to exogenous IFNin vitro.The results do not support the hypothesis that IFN treatment could restore normal Ig production

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01356.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01357.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01358.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY