Transfusion of donor peripheral blood buffy coat cells as effective treatment for relapsed acute leukemia after transplantation of allogeneic bone marrow or peripheral blood stem cells from the same donor

BACKGROUND: The transfusion of same-donor peripheral blood buffy coat (PBBC) cells to chronic myelocytic leukemia patients in relapse after bone marrow transplantation has been increasingly used as an effective antileukemic therapy. A graft-versus-leukemia effect mediated by immunocompetent donor T cells underlies its success. In acute leukemia, however, the effect of this adoptive cellular immunotherapy has not been established, and the results are generally poor. STUDY DESIGN AND METHODS: Five patients, three with acute lymphoblastic leukemia and two with acute myelocytic leukemia, who relapsed within 6 months after allogeneic marrow transplantation were enrolled in a nonrandomized pilot study to receive donor PBBC cell transfusions either before or after undergoing cytoreductive chemotherapy. ABO genotyping and polymerase chain reaction amplification of human tetrameric short tandem repeats DNA typing were used to test for marrow chimerism. RESULTS: Two acute lymphoblastic leukemia patients-both of whom underwent chemotherapy before PBBC cell transfusions, experienced a complete remission, and developed acute and then chronic, extensive graft-versus-host disease-have been leukemia-free for 9 and 7 months, respectively. Repeated molecular studies of their marrow as early as 2 weeks to 8 months after treatment confirmed that the marrow was of donor origin. The other three patients, who chose not to undergo chemotherapy before PBBC cell transfusions, failed to achieve remission and died 14, 16, and 30 days, respectively, after leukemia relapse. CONCLUSION: Adoptive cellular immunotherapy may be effective for acute lymphoblastic leukemia patients in relapse after bone marrow transplantation if chemotherapy is administered before PBBC cell transfusions are initiated.     

镁及镁合金在仿生体液中的腐蚀降解行为

目的:观察纯镁及镁锌系列合金在仿生体液中的腐蚀行为,分析其是否具有生物临床应用价值。方法:实验采用纯镁(99.9%)、镁锌锆(ZK60)、镁锌锆钇(Mg-5.6Zn-0.55Zr-0.9Y)3种合金材料,将试样分别放入仿生溶液中浸泡10d,仿生溶液恒温(37.0±0.5)℃。用BP211D电子天平测量了试样在仿生体液中的腐蚀失重,用LK98BII型电化学系统测量了试样在仿生体液中腐蚀时的Tafel曲线,同时观察仿生溶液pH值的变化结果:①在仿生体液中242h后,纯镁、镁锌锆和镁锌锆钇损失量分别为0.9%,3.1%和抗蚀性1.7%。②在实验条件下,腐蚀电流密度纯镁为2.03mA/mm2,镁锌锆为10.14mA/mm2,镁锌锆钇为4.42mA/mm2。③随着镁合金在仿生体液中浸泡时间延长,溶液的pH值增高,电势也随着pH值的增加而减小,镁及镁合金的腐蚀速率会降低。结论:①合金中杂质元素越少,耐腐蚀性能越好,选择纯镁或含Y的镁合金作为镁基生物材料的耐蚀性较好。②在镁锌合金中添加钇后其耐体液腐蚀性能得到了改善。     

Reduced cerebral vascularization in experimental neuronopathic Gaucher disease

The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β‐glucocerebrosidase, with subsequent accumulation of β‐glucocerebroside, its upstream substrates, and the non‐acylated congener β‐glucosylsphingosine. However, the mechanisms by which end‐organ dysfunction arise are poorly understood. Here, we report strikingly diminished cerebral microvascular density in a murine model of disease, and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β‐glucosylsphingosine. Further in vitro studies confirmed a concentration‐dependent impairment of endothelial cytokinesis upon exposure to quasi‐pathological concentrations of β‐glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end‐organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Anti-i causing acute hemolysis following a negative immediate-spin crossmatch

A unique case of acute hemolysis following transfusion of red cells (RBCs) that were found compatible by immediate-spin (IS) crossmatch technique is reported. Screening tests for unexpected antibodies, using low-ionic-strength saline (LISS), 10 minutes' incubation at 37 degrees C, and anti-IgG, were nonreactive; however, 1 transfused unit was found crossmatch incompatible by indirect antiglobulin technique (IAT). An anti-i (titer 512 at 4 degrees C) that was not an autoantibody was identified in the patient's serum. Unlike the incriminated donor RBCs, most I+ RBCs did not react by LISS-IAT. Variable reactivity was seen with ficin-treated I+ RBCs, and there was marked hemolysis of iadult and icord RBCs. In marked contrast, dominant Lu(a-b-) RBCs, with reduced expression of i, did not react by any test method; nor did autologous I+, Lu(b+) RBCs. The in vivo clinical significance of this anti-i was confirmed by monocyte monolayer assay and RBC survival studies. The patient's i antigen may have been altered, by either chemotherapy or disease, and lacked part of the i antigen-mosaic. Her antibody was directed at epitopes of i that were absent from her RBCs. Those i epitopes missing from her RBCs are also absent on dominant Lu(a-b-) RBCs. This anti-i represents a unique cause of an acute hemolytic transfusion reaction. It also represents a case of acute immune-mediated hemolysis following transfusion of IS crossmatch-compatible blood when screening tests for unexpected antibodies are nonreactive. Because of the rarity of such cases (less than 1/200,000 RBC units transfused), modifications to pretransfusion testing protocols are not proposed.     

Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in human immunodeficiency virus-infected persons

Anemia, thrombocytopenia, and neutropenia have been observed in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. To investigate whether red cells (RBCs) of patients with human immunodeficiency virus infection were coated with IgG and/or complement (C3), blood samples of 239 patients were tested. The prevalence of a positive direct antiglobulin test on RBCs was 16.7 percent. By use of an enzyme-linked antiglobulin test (ELAT) to measure more accurately the number of IgG molecules per RBC in a group of 67 patients, 30 of the 67 individuals were observed to have increased numbers (mean, 155) compared to normal controls and to patients with hypergammaglobulinemia due to multiple myeloma or chronic liver disease. Hemoglobin level was correlated with the number of IgG molecules per RBC (p = 0.008), but no correlation could be demonstrated between those numbers and serum immunoglobulin (p = 0.10) or circulating immune complexes (p = 0.38). Our results with ELAT suggest that some AIDS patients may have specific binding of IgG on the surface of their RBCs, rather than nonspecific uptake; further clinical correlations are necessary to confirm these findings.     

B-cell tolerance. IV. Differential role of surface IgM and IgD in determining tolerance susceptibility of murine B cells

During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a “triggering” isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult splenocytes (which are predominantly μ(+)δ(+)[4-6]) and neonatal splenocytes (which bear predominantly IgM [μp(+); 1, 4-6]) to tolerance induction were compared. The results indicate that neonatal splenic B cells responsive to thymus dependent (TD) antigens are exquisitely susceptible to tolerance induction compared with those from adult mice (7-9). However, cells from both adult and neonatal mice were highly susceptible to tolerance induction when thymus independent (TI) antigen was used as immunogen (8). These results suggest that the major precursor for the TD response is a μ(+)δ(+)-cell which appears late in ontogeny and is resistant to tolerance induction and that the μp(+)-cell is the major precursor for the TI response and is highly susceptible to tolerance induction. Other differences between responders for TI and TD antigens have been described previously (10-12). To test this concept, adult splenocytes were treated with papain under conditions in which IgD, but not five other surface molecules, was removed (13). Such treated splenocytes were shown to be markedly susceptible to tolerance induction, resembling TD responders from neonatal animals. This experiment was interpreted as indicating that IgD confers resistance to tolerance induction on μ(+)δ(+)-cells. To prove this interpretation, it is necessary to show that specific removal of IgD with anti-δ also results in increased susceptibility to tolerance induction and that treatment with anti-μ does not have a similar effect. In the present studies, we have removed surface IgM or IgD by antibody-induced capping and assessed the tolerance susceptibility of the treated cells. Our results demonstrate that removal of IgD, but no IgM, from TD responders increases their susceptibility to tolerance induction.     

中国病毒性乙型肝炎的研究

我国是病毒性乙型肝炎(HB)高发病国家,人群感染HBV约有6.5亿,而HBsAg慢性携带者则为1.2亿,每年死于HB及相关性疾病者在16万人以上,HB已成为我国危害最大的社会公共卫生问题。现就目前我国HB研究的状况,提出一些思考,希望能对HB的研究有所助益。 1 病毒性乙型肝炎的分类我国现行的病毒性肝炎分类方案(以下称分类方案)与国际上基本一致,将其分为急性、慢性和肝炎肝硬变三大类,又根据HB不同的临床体征及组织病理学表现,而分成若干亚型。     

分光光度法测定金蝉花中多糖的含量

目的建立金蝉花药材中多糖的含量测定方法.方法采用分光光度法测定多糖含量.结果金蝉花中多糖含量为24.16 mgg-1,平均回收率为97.37%,RSD＝2.34%,n＝5.结论本法简便、准确、灵敏、重现性好,为金蝉花药材的质量控制提供了依据.     

Genetic control of the circulating concentration of transforming growth factor type beta1

The concentration of transforming growth factor beta (TGF-beta) in plasma has been correlated with the development of several diseases, including atherosclerosis and certain forms of cancer. However, the mechanisms that control the concentration of TGF-beta in plasma are poorly understood. In a study of 170 pairs of female twins (average age 57.7 years) we show that the concentration of active plus acid- activatable latent TGF-beta1 [(a+l) TGF-beta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-beta1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G-->A at position -800 bp and C-->T at position -509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF-beta1, explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1 concentration. It is therefore possible that predisposition to atherosclerosis, bone diseases or various forms of cancer may be correlated with the presence of particular alleles at the TGFB1 locus.