接受气管插管的早产儿气管灌洗液中的NF—κB：与炎症、吸氧和转归的关系

目的：确定气管灌洗液中转录因子NF-κB浓度是否与早产儿的支气管肺发育不良（BPD）相关，NF-κB是由BPD相关的危险因素激活并能诱发BPD相关的细胞因子的表达。设计：在气管插管的早产儿的连续的气管灌洗标本，对细胞计数及白介素（IL）-8和NF-κB浓度进行分析，并通过分泌成分浓度对稀释度进行校正。机构：三级大学医院的新生儿重症监护病房。     

The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells

Growth factor receptors in human hematopoietic progenitor cells have become the focus of intense interest, because they may provide tools for the monitoring, enrichment, and expansion of stem cells. We have shown earlier that the Tie receptor tyrosine kinase is expressed in erythroid and megakaryoblastic human leukemia cell lines, in the blood islands of the yolk sac, and in endothelial cells starting from day 8.0 of mouse development. Here, the expression of Tie was studied in human hematopoietic cells of various sources. Peripheral blood mononuclear cells were Tie-. However, a large fraction of CD34+ cells from umbilical cord blood (UCB) and bone marrow (BM) expressed tie protein and mRNA. On average, 64% of the fluorescence-activated cell sorting- gated UCB CD34+ cells including CD38- cells and a fraction of cells expressing low levels of c-Kit were Tie+. Also, 30% to 60% of BM CD34+ cells were Tie+, including most of the BM CD34+CD38-, CD34+Thy-1+, and CD34+HLA-DR- cells. Under culture conditions allowing myeloid, erythroid, and/or megakaryocytic differentiation, purified UCB CD34+ cells lost Tie mRNA and protein expression concomitantly with that of CD34; however, a significant fraction of cells expressed Tie during megakaryocytic differentiation. These data suggest that, in humans, the Tie receptor and presumably its ligand may function at an early stage of hematopoietic cell differentiation.     

Identification of a cellular polypeptide that distinguishes between acute lymphoblastic leukemia in infants and in older children

We analyzed the polypeptide pattern of leukemic cells of infants and older children with acute lymphoblastic leukemia (ALL), using two- dimensional polyacrylamide gel electrophoresis (PAGE). Patterns were analyzed for the occurrence of a previously detected cytosolic polypeptide, designated L3. Quantitative analysis of L3 in 12 infants and 91 older children with non-T ALL indicated lack of expression of polypeptide L3 in leukemic cells of infants which, in most cases, expressed HLA-DR and CD19 and lacked CD10. Quantitative analysis of L3 in relation to cell surface marker expression revealed that L3 was limited in its occurrence to non-T ALL and was not coordinately expressed with any of the surface markers included in the study. Among patients in the HLA-DR-positive, CD19-positive, and CD10-negative group, different levels of polypeptide L3 were observed between infants and older children. These results indicate differences in leukemic cell constituents between infants and older children with ALL and an otherwise similar cell surface marker phenotype.     

Correction of the platelet adhesion defect in delta-storage pool deficiency at elevated hematocrit--possible role of adenosine diphosphate

Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of dense granule substances in mediating platelet adhesion appears to be more complicated Previous studies in delta-SPD suggested an adhesion defect that was strongly influenced by the patient's hematocrit (Hct) value. To explore further the possibility that red blood cells (RBCs) may influence the role that platelet storage granules play in mediating adhesion at high shear rates, we have measured adhesion (and thrombus formation) throughout a preselected range of Hct values (30% to 60%) in normal subjects and in patients with delta-SPD. The present studies confirm the defect in platelet adhesion in patients with delta-SPD, most significantly at Hct values of 30% to 40%. This defect (but not that of thrombus formation) can be completely corrected by the addition of RBCs. The correction of the platelet adhesion defect by RBCs was specific for delta-SPD; it was not observed in either von Willebrand's disease or thrombasthenia. Studies performed on normal blood under conditions that could be expected to block any effect of ADP on adhesion and an analysis of the type of adhesion defect in delta-SPD suggest that ADP may be involved in the process required for platelet spreading on the subendothelium. The corrective effect of RBCs on platelet adhesion in delta-SPD appears to be chemical rather than physical in nature, possibly due to shear-induced release of RBC ADP or to other recently described properties of RBCs that enhance collagen- induced platelet interactions.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.     

Establishment of a human acute promyelocytic leukemia-ascites model in SCID mice

Acute promyelocytic leukemia (APL) is an interesting model for cancer research because of the presence of the specific PML-RARalpha fusion gene associated with the clinical response to retinoic acid differentiation therapy. To better understand and improve differentiation induction with retinoic acid, we have established a human APL-ascites model in SCID mice using the NB4 human APL cell line. NB4 (1 x 10(6) cells) were transplanted into the peritoneum (IP) of SCID mice for 1 month. NB4 ascites cells (A-NB4) appeared, which were then engrafted in SCID mice periodically for 18 passages at an interval of 3 to 4 weeks with a 100% success rate of tumor induction. The mean survival times of SCID mice transplanted with 1 x 10(6) A-NB4 cells was 21.6 +/- 2.3 days. Analysis of the biologic characteristics of ninth passage NB4 ascitic cells was performed and they were found to have the morphologic, immunologic, cytogenetic, and molecular features of cultured NB4 cells. Furthermore, A-NB4 cells were capable of differentiating when treated with all-trans retinoic acid (ATRA), as manifested by enhanced NBT reduction and CD11b expression. In vivo treatment with ATRA in SCID mice for 4 days also increased NBT reduction by A-NB4 cells. ATRA treatment significantly prolonged survival time in the group after transplantation (28.1 +/- 6.8 to 29.1 +/- 8.4 days) compared with the control (P < .001). Furthermore, treatment with adriamycin, an effective chemotherapeutic drug in APL, had a strong growth suppressive effect on A-NB4 cells. These results demonstrate that this SCID-APL (NB4 ascites cells) model is a useful preclinical system for evaluating new or known drugs in the treatment of APL.