联合应用IL-2和IL-3的基因疗法增强骨髓移植后骨髓细胞毒活性及抗肿瘤效果的实验研究

目的：探讨联合应用成纤维细胞介导ＩＬ２和ＩＬ３的基因疗法对骨髓移植（ＢＭＴ）后荷瘤小鼠抗肿瘤作用的效果及机理。方法：将分别转染ＩＬ２基因及ＩＬ３基因的ＮＩＨ３Ｔ３细胞以单独或联合方式移植至ＢＭＴ的荷瘤小鼠腹腔内８ｄ后，取出小鼠骨髓细胞检测杀伤活性的变化以及ＩＬ２受体的表达，并观察荷瘤小鼠的存活期。结果：ＩＬ３基因治疗虽然可加速ＢＭＴ后造血重建过程，但对骨髓细胞的ＮＫ、ＬＡＫ活性具有一定的抑制作用；ＩＬ２基因治疗可明显提高骨髓细胞的杀伤活性；联合应用基因治疗后荷瘤小鼠骨髓ＮＫ、ＬＡＫ活性及骨髓细胞ＣＤ２５表达升高，明显延长大剂量化疗后接受ＢＭＴ的荷瘤小鼠的存活期。结论：联合应用ＩＬ２和ＩＬ３的基因疗法能协同提高骨髓细胞ＩＬ２受体表达水平，提高骨髓细胞毒活性，增强ＢＭＴ后的抗肿瘤效果。     

Correlation between soluble transferrin receptor and serum ferritin levels following bone marrow transplantation for thalassemia

Abstract: This study analyzes the serum transferrin receptor (sTfR) levels in a series of 230 ex-thalassemics with a follow-up of 1 to 9 years after bone marrow transplantation (BMT) for homozygous β thalassemia. Ex-thalassemics are individuals, cured of homozygous β thalassemia by BMT, who maintain different degrees of iron overload acquired during the pretransplant period. Both in experimental and clinical conditions, sTfR concentrations have been shown to be a quantitative measure of body iron status. This study was carried out to assess whether the level of sTfR may be of help in determining the extent of iron overload in ex-thalassemics. Patients who received the marrow from their HLA-identical sibling donor heterozygous for β thalassemia, namely heterozygous ex-thalassemics, displayed significantly higher levels of sTfR than patients transplanted from their normal sibling donors (normal ex-thalassemics). This finding suggests that increased erythropoiesis, albeit in part ineffective in heterozygous ex-thalassemics, is responsible for the sTfR increment. Both heterozygous and normal ex-thalassemics had significant lower sTfR levels than their heterozygous (p < 0.003) or normal (p < 0.0001) donors, respectively. These differences may be ascribed to the presence of iron overload in ex-thalassemics in comparison to their normal or heterozygous donors who did not present excess of iron in the body. A significant inverse correlation between sTfR and serum ferritin levels (r = –0.54, p < 0.0001) was found when normal ex-thalassemics were considered. In heterozygous ex-thalassemics, the lack of correlation between these two parameters may be explained by the enhanced erythropoietic activity of individuals with thalassemic trait. These results suggest that the level of sTfR may be a useful indicator of iron overload in normal ex-thalassemics.     

基于骨免疫微环境探讨补肾活血方防治绝经后骨质疏松症的研究进展

骨质疏松症（OP）是我国人群中最常见的多发病,好发于绝经后的老年妇女,增加了患者骨折的风险。绝经后骨质疏松症（PMOP）是一种以骨量减少和骨折风险增加为特征的全身性疾病,主要是绝经后雌激素水平显著降低导致的。除了雌激素缺乏对骨骼的直接负面影响外,绝经后妇女免疫状态的改变间接导致骨骼的持续破坏,因为绝经后妇女通常表现出慢性低级别炎症表型,细胞因子表达和免疫细胞谱发生改变。PMOP已严重危害我国女性健康。补肾活血方是一种应用广泛的补肾活血中药,近年来,随着我国临床医师与患者越来越重视中医药,补肾活血方被应用于多种疾患,包括骨科的多种疾病,其对PMOP的防治效果亦明显。该文基于骨免疫微环境,以骨代谢对PMOP产生影响为基础,论述补肾活血方的作用机制。     

Content of acid and alkaline phosphatases in lymphocytes of peripheral blood and hematopoietic organs of intact rats and mice

The content of acid and alkaline phosphatases was studied in the lymphocytes of the peripheral blood, bone marrow, and lymphoid organs (thymus, spleen, lymph node) of intact noninbred rats. The mean percentage of cells containing the enzymes was determined. Their organ and species characteristics are described.Central Research Laboratory and Department of Pathophysiology, Tomsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR I. V. Toroptsev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 158–159, February, 1978.     

Evaluation of stromal metalloproteinases and vascular endothelial growth factors in a spontaneous metastasis model

This study aims to investigate MMP2 and MT1-MMP protein as well as VEGF-C and VEGF-D mRNA expression in tumor cells and distant organs considered to be targets for metastasis in a tumor spontaneous metastasis model previously described. Cultured tumor cells, able to express pro-MMP2, MMP2, pro-MMP9, and MT1-MMP, develop tumor growth and metastasis, mainly in the liver and spleen, when they are injected in the mammary pad gland of Wistar rats. Immunohistochemical studies of tumor masses showed small groups of tumor cells staining for MT1-MMP but not for MMP2. In the liver, tumor metastatic foci and a stromal positive staining for both MMP2 and MT1-MMP were shown. The spleen and lymph nodes, with only scattered metastatic cells, did not show MMPs immunostaining. Using RT-PCR, a significantly higher VEGF-C and VEGF-D gene expression was shown in the liver of tumor-bearing rats respect to normal rats, whereas spleen and lymph nodes did not show significant differences in mRNA VEGF-C/D levels. Taken together, our results suggest that the stroma microenvironment of target organs for metastasis has the ability to produce MMPs and VEGFs that facilitate the anchorage of tumor cells and promote tumor cell growth and angiogenesis.     

Psychosocial predictors of distress in parents of children undergoing stem cell or bone marrow transplantation

OBJECTIVE: To examine psychosocial predictors of distress (mood disturbance, perceived stress, caregiver burden) in parents of children undergoing stem cell or bone marrow transplantation (BMT). METHOD: Measures of prior illness experiences, premorbid child behavior problems, family environment, social support, and parental coping behavior were obtained from the resident parents of 151 children prior to the children's admission for BMT. Parents subsequently completed assessments of their mood disturbance, perceived stress, and caregiving burden on a weekly basis through week +6 post-BMT, and then monthly through month +6 post-BMT. RESULTS: Significant changes were observed in parental distress across the course of BMT. After correcting for demographic and medical factors, several significant predictors of parental distress trajectories were identified, including prior parent and patient illness-related distress, premorbid child internalizing behavior problems, the family relationship dimensions of the family environment, and parental avoidant coping behaviors. Multivariable models were developed using a hierarchical modeling approach. The best-fit model accounted for approximately 50% of the variance in parental global distress. CONCLUSIONS: Subgroups of parents at higher risk for increased distress during the acute phase of transplant have been identified. These findings can help target parents who may be in greater need of intervention aimed at reducing transplant-related distress.     

Infection of stromal and hemopoietic precursor cells with lentivirus vector <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

We developed a method for gene transfer into mesenchymal stromal cells. Lentivirus vector containing green fluorescent protein gene for labeling stromal and hemopoietic precursor cells was obtained using two plasmid sets from different sources. The vector was injected into the femur of mice in vivo and added into culture medium for in vitro infection of the stromal sublayer of long-term bone marrow culture. From 25 to 80% hemopoietic stem cells forming colonies in the spleen were infected with lentivirus vector in vivo and in vitro. Fibroblast colony-forming cells from the femoral bones of mice injected with the lentivirus vector carried no marker gene. The marker gene was detected in differentiated descendants from mesenchymal stem cells (bone cavity cells from the focus of ectopic hemopoiesis formed after implantation of the femoral bone marrow cylinder infected with lentivirus vector under the renal capsule of syngeneic recipient). In in vitro experiments, the marker gene was detected in sublayers of long-term bone marrow cultures infected after preliminary 28-week culturing, when hemopoiesis was completely exhausted. The efficiency of infection of stromal precursor cells depended on the source of lentivirus. The possibility of transfering the target gene into hemopoietic precursor cells in vivo is demonstrated. Stromal precursor cells can incorporate the provirus in vivo and in vitro, but conditions and infection system for effective infection should be thoroughly selected. __________ Translated from Kletochnye Tehnologii v Biologii i Meditsine, No. 1, pp. 25–28, January, 2007     

47例骨髓穿刺干抽的临床和病理分析

分析４７例骨髓穿刺干抽的临床和病理改变，干抽占同期１３１９例骨穿的３．６％。根据骨髓细胞的密度和间质纤维增殖的程度，把干抽的原因分为４类：高细胞伴间质细胞增多者１９例（４２．２％）；间质细胞增多者１４例（３１．１％）；高细胞者８例（１７．８％）及低细胞者４例（８．９％）。主要疾病为：急性淋巴细胞白血病（２５．５％），急性非淋巴细胞白血病（１７．０％），慢性白血病（１４．９％），骨髓转移瘤（１０．６     

Role of the stromal microenvironment in regulation of bone-marrow hematopoiesis after administration of dipyridamole

I. P. Pavlov First Leningrad Medical Institute. Central Roentgeno-Radiological Research Institute, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 7, pp. 98–100, July, 1990.     

Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.