Effect of Granulocyte Colony-Stimulating Factor on Chemotherapeutic Activity of Cytosine Arabinoside in Acute Leukemic Cell Lines

Recent studies have shown the presence of receptors for granulocyte colony-stimulating factor (G-CSF) on lymphoid leukemic cells. To determine the effect of G-CSF on chemotherapeutic activity of cytosine arabinoside (Ara-C) on lymphoid as well as myeloid leukemic cells, we evaluated cell counts, apoptosis, and growth inhibition in HL-60, KG-1, Molt-4, Jijoye, and CCRF-CEM cell lines after incubation with Ara-C (0.1 and 1 micromol/L) and/or 5 ng/mL G-CSE G-CSF potentiated the effect of Ara-C on 2 of 3 lymphoid leukemic cell lines (Molt-4 and Jijoye), whereas it decreased the apoptosis and the effect of Ara-C on myeloid cell lines (HL-60 and KG-1).     

Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity

A detailed family study was undertaken of patients notified to the UK Diamond Blackfan Anaemia (DBA) Registry. RPS19 mutations were detected in 16 of 104 families, including two patients with deletions detected by intragenic loss of heterozygosity of tightly linked polymorphisms. In two further cases, polymorphisms were used to determine the parental allele of origin of RPS19 point mutations. A review of clinical details of patients with mutations and patients in the literature having identical or equivalent mutations revealed evidence for a genotype:phenotype correlation with respect to the prevalence of physical anomalies, and the occurrence of mild or variable haematological severity. Nine of 60 patients had a known family history of DBA. Haematological abnormalities, including raised red cell adenosine deaminase activity, were found in first-degree relatives of 16 of 51 (31%) of patients not previously considered to have familial DBA. Results of both parents and any siblings were normal in only 35 of 60 (58%) of cases, who were therefore assumed to have sporadic de novo DBA. The classical inheritance pattern for DBA is autosomal dominant; however, 12 of 60 families (20%) had more than one affected child despite normal results in both parents. These results have important implications for genetic counselling, and for the selection of potential sibling bone marrow donors.     

联合检测ADA、CA125和CEA对结核性与恶性胸腔积液的诊断价值

目的 探讨联合检测胸腔积液中腺苷脱氨酶(ADA)、糖类抗原125(CA125)和癌胚抗原(CEA)对结核性与恶性积液的鉴别诊断价值.方法 采用酶连续监测法和化学发光免疫分析法检测82例结核性积液及56例恶性胸腔积液中ADA、CA125和CEA的水平,并对检测结果进行综合分析.结果 结核性胸腔积液中平均ADA含量明显高于恶性胸腔积液,而CEA和CA125平均水平明显低于恶性胸腔积液(P＜O.05).以ADA＞40U/L为临界值,对结核性积液的敏感性、特异性和准确性分别为82.8％,80.4％和81.7％.以CA125＞35U/ml和CEA＞5μg/L为临界值,对恶性积液诊断的敏感性分别为82.6％和71.7％,特异性分别为58.8％和82.8％,准确性分别为65.4％和76.0％;联合检测CA125和CEA诊断恶性胸腔积液的敏感性和准确性分别为93.5％和81.7％,显著高于单一检测项目(P＜O.05).结论 联合检测胸腔积液中ADA、CEA和CA125对早期鉴别诊断结核性与恶性胸水的有重要参考价值.     

Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies

Humoral immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp) is associated with failure to respond to common pathogens and high frequency of autoimmunity. Here we addressed the question how deficiency in WASp and the homologous protein N-WASp skews the immune response towards autoreactivity. Mice devoid of WASp or both WASp and N-WASp in B cells formed germinal center to increased load of apoptotic cells as a source of autoantigens. However, the germinal centers showed abolished polarity and B cells retained longer and proliferated less in the germinal centers. While WASp-deficient mice had high titers of autoreactive IgG, B cells devoid of both WASp and N-WASp produced mainly IgM autoantibodies with broad reactivity to autoantigens. Moreover, B cells lacking both WASp and N-WASp induced somatic hypermutation at reduced frequency. Despite this, IgG1-expressing B cells devoid of WASp and N-WASp acquired a specific high affinity mutation, implying an increased BCR signaling threshold for selection in germinal centers. Our data provides evidence for that N-WASp expression alone drives WASp-deficient B cells towards autoimmunity.     

胞嘧啶的153Sm标记及其用于肿瘤体内显像的可行性

目的 探讨利用放射性核素153Sm体外标记胞嘧啶进行肿瘤代谢显像的可行性.方法 胞嘧啶与DTPA的偶联产物C-DTPA,经纯化后体外标记153Sm,并对得到的显像剂C-DTPA-153 Sm的质量规格进行检测:①制剂要求:检菌,热原检测;②毒理学:急性毒理测定;③特殊参数:标记率,体外稳定性;④药动学:家兔血浆药物代谢动力学;⑤药效学:体外细胞显像,荷瘤小鼠显像.结果 体外实验、动物实验显示C-DTPA-153Sm为无菌、无热原、无毒性的安全制剂,并且可以在肿瘤部位浓集.结论 153Sm标记胞嘧啶代谢显像方法对多种肿瘤有诊断价值,可以无创性的体内评价肿瘤的增生状态,具有重要的临床应用价值.     

Repeatability of pleural adenosine deaminase measurements in diagnostic evaluation of pleural effusions

Background

A follow‐up thoracentesis is proposed in suspected atypical tuberculosis cases. The study aimed to define the variability of pleural ADA values across repeated thoracenteses in different types of pleural effusions (PEs) and to evaluate whether ADA variance, in regard to the cutoff value of 40 U/L, affected final diagnosis.

Methods

A total of 131 patients with PEs of various etiologies underwent three repeated thoracenteses. ADA values were subsequently estimated.

Results

82% and 55% of patients had greater than 10% and 20% deviation from the highest ADA value, respectively. From those patients who had a variance of 20%, 36% had only increasing ADA values, while 19% had only decreasing values. Considering the cutoff value of 40 U/L, only in two cases, ADA decreased below this threshold, which concerned a man with tuberculous pleurisy and a woman with lymphoma both in the course of treatment. Furthermore, only in two cases with rising values, ADA finally exceeded the cutoff limit, which concerned a man with rheumatoid pleurisy and a man with tuberculous pleurisy. Surprisingly, malignant PEs (MPEs) showed a higher percentage of increasing values compared to all other exudates that did not, however, exceed the threshold.

Conclusion

The determination of pleural ADA levels is a reproducible method for rapid tuberculosis diagnosis. The detected measurement deviations do not appear to affect final diagnosis. In specific situations, repeated ADA measurements may be valuable in directing further diagnostic evaluation. More investigation is needed to elucidate the possible prognostic significance of the increasing trend in ADA values in MPEs.

     

Rheumatoid arthritis and anti-thyroid antibodies

The aim of this study was to evaluate the quality of B cell responses in patients with Inflammatory Bowel Disease (IBD) and healthy individuals of different ages, vaccinated with the pandemic (p)2009 influenza vaccine. The in vivo response was measured by the hemagglutination inhibition (HAI) assay, which represents the most established correlate with vaccine protectiveness. The in vitro response was measured by activation-induced cytidine deaminase (AID) in cultures of vaccine-stimulated PBMC. Both responses are somewhat impaired in IBD patients undergoing anti-TNF-α treatment but these are much more decreased in IBD patients undergoing treatment with anti-TNF-α and immunosuppressive (IS) drugs. These latter patients had in vivo and in vitro B cell responses similar to those of elderly individuals. Moreover, as we have previously demonstrated in healthy subjects, the in vitro response to the polyclonal stimulus CpG may be used as a biomarker for subsequent vaccine response and AID activation is correlated with the serum response in IBD patients, as it is in healthy individuals. These results altogether indicate that IBD patients on anti-TNF-α and IS have significantly impaired in vivo and in vitro B cell responses, as compared to those on monotherapy. This is the first report to demonstrate that B cell defects, as measured by the autonomous AID reporter, in IBD patients contribute to reduced humoral responses to the influenza vaccine, as we have previously shown for elderly individuals.     

VAGINAL IMMUNITY IN THE HSV-2 MOUSE MODEL

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that infects the genital tract. Efforts to develop vaccines to protect women against this and other sexually transmitted pathogens would be facilitated by a better understanding of the immune mechanisms that protect the female reproductive tract against such infections. Such information would be invaluable in developing vaccine strategies to promote the type and magnitude of immune responses in the genital tract that would effectively protect against infection. This review focuses on recent studies using a progestin-treated adult mouse model to explore mucosal immunity to HSV-2 in the vagina. Evidence indicating a major role for both humoral and T cell immunity is presented.     

CD26 a cancer stem cell marker and therapeutic target

Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target.