Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

Is growth hormone a radioprotective agent?

There is currently substantial clinical interest in growth hormone (GH) as a protective agent against radiation-related normal tissue injury. To further assess the potential radiation injury-preventive effects of GH, these effects were studied in rats by using a radiation-induced skin injury model. Group 1 received neither GH nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (radiation group). Group 3 and 4 received the same irradiation plus either 0.01 U/kg/day GH (RT + 0.01 GH group) or 0.02 U/kg/day GH (RT + 0.02 GH group) subcutaneously. Clinically and histopathologically, acute skin reactions were assessed by two independent experts in radiation oncology and pathology, respectively. Irradiation increased dermatitis in rats when compared with the control group. The severity of radiodermatitis in the rats in the RT + 0.01 GH and RT + 0.02 GH groups was significantly lower than that in the RT group; radiodermatitis developed earlier in the RT group than in the other groups. GH was efficacious in preventing epidermal atrophy, dermal degeneration such as oedema and collagen fibre loss, and hair follicle atrophy, but not better than in the control group. These results are preliminary to studies that will be performed with higher doses of GH in radiation-treated cancer patients, with the aim of reducing radiation-induced toxicity.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

体表高频超声技术评价家兔血管成形术后再狭窄模型与病理学结果的相关性

目的:分析体表高频超声检测家兔血管内球囊成形术后再狭窄程度与组织病理学分析的相关性。评估体表超声检测的可行性、可靠性及应用价值。方法:实验于2002-03/2003-12在北京中医药大学中医内科学重点学科实验室完成。①日本大耳白兔26只,随机分为正常组10只、假手术组6只、模型组10只。②模型组电刺激兔颈总动脉,电流1.2mA,刺激12～15min,术后第2天喂饲高脂饲料共8周,假手术组仅剥离颈总动脉,不做电刺激,喂高脂饲料,正常组不施加任何干预因素。③模型组和假手术组根据B超选择颈总动脉有斑块或血流明显改变者行球囊血管内成形术。分别于电刺激后8周、血管成形术后4周行超声检查动脉内径和动脉内膜厚度。④所有动物于血管成形术后4周处死取材,进行病理学半定量分析,并与超声测量结果进行相关分析。结果:进入结果分析数量24只,正常组中途死亡1只,原因为牙齿畸型影响进食。模型组1只因电刺激8周时超声评价颈动脉未形成斑块及血流无明显改变而剔出实验。①超声检测电刺激8周时正常组内膜厚为(0.028±0.004)cm,模型组管壁明显增厚(0.043±0.014)cm,差异有显著性(P<0.05),至血管成形术后膜厚增加更明显(0.064±0.002)cm,内径稍有扩大,但差异不显著。②超声检测模型组颈动脉内径与膜厚的测量结果与病理学测量结果呈正相关关系(OR=0.361,P<0.05;OR=0.526,P<0.01),病理狭窄率与超声是否检测到斑块呈正相关关系(OR=0.796,P<0.01)。结论:体表高频超声在评价家兔颈动脉狭窄诊断中有一定应用价值,与病理学半定量分析结果相关性良好。     

Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice

Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer''s (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27 mm Hg for 35 minutes. Mice (n=10/group) were then resuscitated with a 20 mL/kg bolus of 4% PNPH or LR followed by 10 mL/kg boluses targeting MAP>70 mm Hg for 90 minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7 mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83 mm Hg, P<0.001). The PNPH-treated mice required only 20 mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12 mm Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68 mm Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development.     

Erythropoietic stress, macrocytosis, and hemoglobin switching in HbAA sheep

Hemoglobin switching and macrocytosis were studied in homozygous hemoglobinAA sheep. An abrupt initiation of erythropoietic stress, accompanied by a pulsed elevation of circulating erythropoietin levels, was induced by phlebotomy. Sequential blood samples were separated according to density on Stractan gradients to isolate cells newly entering the circulation from the marrow each day. Analysis of hemoglobin phenotype and cell volume distribution in these young reticulocytes revealed a distinct temporal separation in the appearance of hemoglobin C and increased cell volume. The appearance of macrocytes within 24 hr of erythropoietin elevation suggests that macrocytosis could be the result of the action of erythropoietin during the late stages of erythroid maturation. The 72-hr delay in the appearance of hemoglobin C indicates that commitment to a particular hemoglobin phenotype occurs at an early stage of differentiation and involves immature erythroid stem cells. The results of this study show that these consequences of erythropoietic stress are initiated at two different developmental stages, resulting in the production of macrocytosis and hemoglobin switching.