摘要:

Abstract:The polymorphonuclear leukocyte (PMN) plays an essential role in the innate defense of the mammalian host against bacterial invaders. Responding chemotactically, the PMN delivers a complex antibiotic arsenal to sites of infection. Among these cytotoxic systems is an array of antimicrobial proteins and peptides that the PMN directs at microorganisms both before (i.e. extracellularly) and after sequestration into a phagocytic vacuole. In addition to their microbicidal capacity, several of these proteins bind to and neutralize the endotoxic activity of Gram‐negative bacterial lipopolysaccharides (LPS). In this review the principle features of these antibiotic proteins are briefly summarized with emphasis on their possible actions in biological settings. In many instances, additional functions independent of cytotoxicity have been described raising the possibility that some of these proteins subserve multiple roles in inflammatio

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Very high‐dose chemotherapy with autologous blood stem cell (BSC) rescue becomes more and more widely performed. In order to simplify the technique, a large volume apheresis programme combined with an uncontrolled rate cryopreservation at –80°C was developed. Twenty‐six patients suffering from multiple myeloma (n= 8), non‐Hodgkin's lymphoma (n= 7), dysgerminoma (n= 4), breast cancer (n= 3), Hodgkin's disease (n= 2), acute lymphoblastic leukaemia (n= 1) and acute myelocytic leukaemia (n= 1) were autografted after a classical high‐dose chemotherapy regimen. A single large volume apheresis was sufficient to obtain the threshold value of CD34+ BSC in 24/26 transplantations. The haematological recovery was favourably comparable with the previously published data obtained with controlled rate frozen BSC: median time to granulocytes>1000/μL and to a self‐supporting platelet count>20,000/μL, respectively, 10.5 and 12 d. The treatment‐related mortality was confined to 1/26 BSCT. These results indicate that this easy and cost‐saving policy of BSCT is efficacious and safe: sustained long‐term haematopoiesis, reduced morbidity and mor

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Systemic amyloidosis may often be complicated with haemorrhagic tendency. The causes of this manifestation are factor deficiencies, hyperfibrinolysis and vasculopathy. In order to investigate the role of platelets, if any, we performed platelet aggregation tests with different aggregants in 10 patients with systemic amyloidosis due to familial Mediterranean fever and 10 healthy controls. Platelet aggregation was defective with different aggregants (ADP, epinephrine, collagen) in patients compared with controls. Platelet aggregation tests repeated after desmopressin (DDAVP) administration were normalized. These findings may suggest a role of a platelet aggregation defect in haemorrhagic diathesis complicating systemic amyloidosis. DDAVP may benefit patients with this disease in case of bleeding and before surgical interventions.

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Megakaryocyte (MK) ploidy patterns were analysed by flow cytometry in 29 newly diagnosed and previously untreated patients with chronic myeloproliferative disorders (MPD) and concomitant thrombocytosis, in 9 patients with reactive thrombocytosis (RT) and in 12 healthy individuals. Unfractionated bone marrow from routine aspirates was used. MKs were identified with a fluorescein labelled monoclonal antibody specific for glycoprotein IIIa (GPIIIa) and DNA was stained with propidium iodide. For the 12 healthy volunteers the mean modal ploidy number was 16 N; the 9 patients with RT displayed an identical MK ploidy pattern. The frequency of MKs with a ploidy ≥32 N was 45% among the patients with essential thrombocythaemia (ET) compared to 32% among the healthy volunteers (p<0.001). MKs with ploidy number ≥ 64 N, comprising approximately 13% of the total number of MKs, was a characteristic finding in the patients with ET. Similar findings were present in 8 patients with polycythaemia vera (PV). In patients with PV 34% and 6% of the MKs displayed ploidies ≥32 N and ≥64 N, respectively. In contrast, a distinct shift towards lower ploidy number, with 63% of MKs ≤ 8 N, was found among the 4 patients with chronic myeloid leukaemia (CML). The present results indicate that by using flow cytometric analysis of MK ploidy distribution in patients with thrombocytosis, those with a reactive cause are likely to be discriminated from patients with myeloproliferative thrombocytosis, i.e. PV and ET on one hand and CML on the other hand. The distinction between ET and PV, however, has to be made on othe

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:To determine the frequencies and differential counts of megakaryocytes after cytoreductive treatment in nucleated low‐density (1.060 g/ml) bone marrow cells (BMNC) of dogs an immunogold‐silver staining (IGSS) technique with the lineage specific monoclonal antibody 2F9 was established. This antibody recognizes the glycoprotein IIb/IIIa complex expressed on the surface of canine megakaryocytes and platelets. The IGSS technique enables not only the detection of megakaryocytes occurring at a low frequency (0.1–0.2%), but also the discrimination between the different maturation stages of megakaryocytes due to cell size, nuclear morphology and cytoplasmic staining. By the use of this technique, small lymphoid megakaryocytic cells were identified. Comparable numbers of megakaryocyte colony‐forming cells in 2F9‐depleted and nondepleted BMNC suspensions (25.7 + 5.0 vs. 25.3 ± 5.1 Meg‐CFC/105BMNC) indicate that these small 2F9 positive cells are nonclonogenic precursors of megakaryoblasts. To prove the applicability of IGSS, serial examinations of bone marrow samples from dogs treated with recombinant human interleukin‐6 (IL‐6) after exposure to 2.4 Gy total body irradiation (TBI) were performed. The results of the microscopic evaluation indicate that, in the recovery phase after TBI, IL‐6 induced an earlier and stronger increase in megakaryocyte frequency in comparison to the control. Interestingly, all maturation stages of the megakaryocytic lineage took part in this IL‐6 induced improvement of me

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:We performed a prospective study in 17 consecutive patients following autologous bone marrow (BM) or rhG‐CSF primed peripheral blood stem cell (PBSC) transplantation, with the objective of comparing immune recovery between both procedures and to evaluate results in rhG‐CSF mobilized peripheral blood stem cell transplantation (PBSCT). Kinetics of immune reconstitution showed differences, with a faster recovery of CD3+ and CD8+ T cells, and a more rapid and sustained recovery of CD8±/CD56+ natural killer (NK) cells in the PBCSCT group. Autologous bone marrow transplantation (ABMT) was associated with a improved reconstitution of the CD19+/CD5±subpopulation. Moreover, rhG‐CSF mobilized PBSCT generated a greater recovery of CD8±/CD56+ cells than previous data concerning transplantation with peripheral blood (PB) progenitors collected after myelosuppressive chemotherapy or myelosuppressive therapy plus rhG‐CSF. Our results show differences in the rate and pattern of B and T lymphocytes reconstitution after ABMT and PBSCT. Additionally, we state an enhancement of CD56+ cells in patients undergoing PBSCT mobilized solely usi

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Thirteen consecutive adult patients with primary refractory (n= 5) or relapsed (n= 8) acute lymphoblastic leukemia (ALL) were treated by an induction schedule (FLAG) consisting of Fludarabine (30 mg/sqm/d) plus high dose Cytarabine (HD‐ara‐C: 2 g/sqm/d) (d 1–5) and G‐CSF (from d 0 to polymorphonuclear recovery). Patients achieving complete remission (CR) were administered a second FLAG course as consolidation and were then submitted to an individualized program of post‐remission therapy, depending on the patient's age and performance status. CR was achieved in 8/12 evaluable cases (67%). The median CR duration was 22.5 w. CR attainment was significantly related to the co‐expression of lymphoid and myeloid antigens. ALL/My+ patients achieved CR in 6/6 evaluable cases vs. 2/6 for ALL/My‐.In vitro3H ara‐C incorporation into cellular DNA resulted significantly increased by Fludarabine (in 7/9 tested cases) and, furthermore, by the association of Fludarabine‐G‐CSF in 5 evaluable ALL/My+ cases; in contrast, no effect of G‐CSF addition to Fludarabine was observed in 4 ALL/My–. Myelosuppression was observed in all patients: the median time to neutrophils>0.5 × 109/l was 16.3 d (range 13–22) and 16.2 d (range 9–29) to platelets>20 × 109/l. Nonhematological toxicity was minimal. In conclusion, FLAG is an active and tolerable combination in refractory ALL, particularly in cases with myeloid antigen expression where G‐CSF appears to improve efficacy, probably increasing ara‐C incorporati

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The cell cycle regulators p16INK4and p15INK4Bhave been mapped to the minimal region of overlap for chromosome 9p21 deletions, observed in a number of malignancies, suggesting that they could be tumor suppressor genes (TSGs). In the case of pl6INK4this has been further substantiated by the finding of small intragenic mutations. In this study we have investigated the p16INK4and p15INK4Bgenes in 16 malignant T‐cell lines by means of Southern blot, PCR and sequence analysis. p16INK4allelic deletions occurred in 15 of 16 cell lines; 12 of which were homozygous and 3 hemizygous. In 1 cell line (DND 41) the remaining p16INK4allele carried a microdeletion of 29 bp of exon 2, supporting the concept that p16INK4is a target TSG for deletions on 9p21. Most p16INK4deletions also included the p15INK4Bgene. However, 4 of the cell lines deleted for p16INK4showed no evidence of p15INK4Bloss, indicating that p15INK4Bis not the target in these cell line

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb00721.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.tb00722.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.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY