Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels

Endovaginal sonography results were compared with quantitatively determined human chorionic gonadotropin (hCG) levels in 84 women referred for early pregnancy complications. Of the 27 with normal intrauterine pregnancies, an intrauterine gestational sac was prospectively identified in one of five cases (20%) in which hCG levels were below 500 IU/L (Second International Standard), four of five (80%) with hCG levels of 500-1,000 IU/L, and all 17 with hCG levels above 1,000 IU/L. In comparison, 17 of the 26 women with ectopic pregnancies (65%) had hCG levels greater than 1,000 IU/L, and none of the 26 had an intrauterine gestational sac. Endovaginal sonography demonstrated an adnexal mass and/or a gestational sac-like structure in 16 of the 17 cases (94%) in which hCG levels were above 1,000 IU/L, compared with only three of the nine (33%) with lower hCG levels (P less than .01). These findings indicate that an intrauterine gestational sac should be normally visualized with endovaginal sonography when the hCG level exceeds 1,000 IU/L, and that visualization of an extrauterine gestational sac and/or adnexal mass is significantly more likely in ectopic pregnancies when the hCG level exceeds 1,000 IU/L.     

马兜铃酸的倍半萜的酯类化合物VI.绵毛马兜铃中马兜铃酸萜酯I的结构鉴定

从绵毛马兜铃(Aristolocha mannisima Hance)中分得一个马兜铃酸倍半萜的酯类化合物,经红外、紫外、高分辩质谱和多种一维和二维核磁共振谱鉴定,确定了其骨架结构及顺反构型,命名为马兜铃酸萜酯I。     

Hemolytic warm IgM autoagglutinins in autoimmune hemolytic anemia

The authors report a patient with fulminant autoimmune hemolytic anemia due to a rare warm IgM autoagglutinin more reactive at 37 degrees C than at lower temperatures and secondary to systemic lupus erythematosis. The patient's clinical course and the serologic and immunochemical characteristics of the antibody are described, including the possibility that transfusions of small amounts of incompatible red cells may have contributed to the hemolysis. The consequences of using the initial serologic test results as the basis for therapy are discussed.     

White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis

This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

经冠状动脉移植自体骨髓单个核细胞和间充质干细胞对急性心肌梗死模型心功能的改善

目的:为保护濒死心肌提供机会窗口,对比观察经冠脉移植自体骨髓单个核细胞或间充质干细胞后,实验性急性心肌梗死动物心功能变化及心肌组织核转录因子кB、心肌细胞凋亡情况。方法:实验于2005-03/2006-11在河北省人民医院实验中心完成。选用24只雄性冀中白猪,随机数字表法分为4组:正常对照组、模型组、单个核细胞组、间充质干细胞组,6只/组。①24只猪均以盐酸氯胺酮200mg臀部肌肉注射麻醉后,分别于各自右侧股骨抽取骨髓20mL,采用Fercoll法分离获得骨髓单个核细胞,加入胶体金溶液,培养12～16h待用。分离过程中取出含有骨髓单个核细胞成分的细胞层,常规培养传代,每3d换液1次,贴壁生长细胞即为骨髓间充质干细胞,加入胶体金溶液,培养24h待用。②除正常对照组外,其余各组均经导管球囊封闭第一对角支以远的前降支,复制猪急性心肌梗死模型。单个核细胞组、间充质干细胞组均于造模后立即开通前降支,分别经球囊注入预先分离的骨髓单个核细胞6×108个、间充质干细胞6×108个。模型组造模后于梗死1h开通前降支,经球囊注入磷酸盐缓冲液10mL。③各组分别于术前及术后4周经心脏超声检测心功能,取材行病理学检查、心肌组织核转录因子кB的免疫组织化学检测及心肌细胞凋亡检测。结果:24只雄性白猪均进入结果分析。①心功能变化:术前各组左心室收缩末内径、左心室舒张末内径、左心室射血分数、短轴缩短率基本相似。移植术后4周,正常对照组、单个核细胞组、间充质干细胞组左心室舒张末内径均明显低于模型组(F=4.68,P=0.01),左心室射血分数及短轴缩短率均明显高于模型组(F=5.14,P=0.01;F=3.32,P=0.04),各组左心室收缩末内径差异无显著性意义(F=1.64,P=0.21)。②心肌组织病理学改变:电镜下单个核细胞组、间充质干细胞组在梗死边缘区可见有胶体金颗粒的不成熟的心肌细胞,胞质中散在肌丝结构,肌丝排列紊乱不规则。③心肌组织核转录因子кB阳性率表达:与模型组比较,单个核细胞组、间充质干细胞组的梗死边缘区核转录因子кB阳性率明显降低(F=25.59,P=0.0001);正常心肌区核转录因子кB阳性率亦明显降低(F=18.20,P=0.0001)。④心肌细胞凋亡检测结果:与模型组比较,单个核细胞组、间充质干细胞组在心肌梗死区细胞凋亡率均明显降低(F=6.63,P=0.0027),梗死边缘区细胞凋亡率亦明显降低(F=36.07,P=0.0001)。正常心肌区单个核细胞组细胞凋亡率与模型组基本相似(F=9.69,P=0.004),但间充质干细胞组有所降低。⑤心功能与心肌细胞凋亡及心肌组织NF-кB的相关性:急性心肌梗死4周时,左心室射血分数与心肌细胞凋亡、心肌组织核转录因子кB均呈负相关(r=0.613,P=0.001;r=-0.437,P=0.033)。心肌细胞凋亡与心肌组织核转录因子кB呈正相关(r=0.672,P=0.002)。结论:经冠脉移植骨髓单个核细胞和间充质干细胞均可改善实验性急性心肌梗死动物的心功能,与梗死边缘区核转录因子кB表达降低及心肌细胞凋亡减少有关。骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植。