Transfusion of donor buffy coat cells in the treatment of persistent or recurrent malignancy after allogeneic bone marrow transplantation

BACKGROUND: Patients who experience relapse after allogeneic bone marrow transplantation have a poor prognosis. However, preclinical and clinical data have strongly suggested the existence of an immune- mediated anti-tumor effect of allogeneic bone marrow transplantation. This effect, termed graft-versus-leukemia, may be harnessed purposefully in patients with posttransplant relapses by the administration of immune cells obtained by leukapheresis of the original bone marrow donor. STUDY DESIGN AND METHODS: Thirteen patients with persistent or recurrent hematologic malignancy after HLA-matched sibling-donor allogeneic bone marrow transplantation were treated with transfusion of buffy coat cells collected from the original bone marrow donors. Mononuclear cell dose ranged from 1.18 to 4.28 × 10(8) per kg. Alpha-interferon (1.5-3 × 10(6) U/m2 3-5x/week) was given to seven patients. Patients were observed for the development of graft-versus- host disease and disease response. RESULTS: Three of five patients with chronic myelogenous leukemia had complete remissions. One of five patients with active acute leukemia attained complete remission. A sixth acute leukemia patient treated with buffy coat transfusion after the induction of remission with chemotherapy relapsed 12 months later. One patient with myeloma had a complete but transient response. A patient with Hodgkin's disease did not respond. Four patients remain in remission 4, 16, 17, and 29 months after attaining complete remission. Graft-versus-host disease occurred in eight patients, including all of those with a complete response. One patient developed transient pancytopenia. CONCLUSION: The transfusion of donor buffy coat cells has significant anti-tumor activity in patients with relapsed hematologic malignancy after allogeneic bone marrow transplantation. This effect is strongly associated with graft-versus-host disease.     

左归丸药物血清对骨髓间质细胞转化为肝细胞的作用

目的:一些实验已证实骨髓干细胞可以向肝细胞横向分化,观察补肾中药左归丸含药血清对骨髓间质细胞分化为肝细胞的影响。方法:实验于2002-01/2004-12在湖北中医学院附属医院肝病研究所完成。①实验动物:选取SPF级纯系Wistar大鼠46只,1只用于骨髓间质细胞的分离及培养,剩余45只用于含药血清的制备。另取2d龄Wistar乳鼠20只,用于肝脏细胞的培养。②实验方法:以体外肝细胞培养上清为诱导条件培养液,采用贴壁分离法纯化大鼠骨髓间质细胞。45只Wistar大鼠依次取15只用生理盐水、中药左归丸(由熟地、淮山药、枸杞子、山茱萸、菟丝子、川牛膝、鹿角胶、龟版胶组成)浓缩煎剂、中药八珍汤(由人参10g,白术10g,茯苓10g,甘草6g,当归15g,川芎10g,白芍15g,熟地15g组成)浓缩煎剂按10mL/kg灌胃,灌胃量以生药10g/kg计算,1次/d。第15天灌胃后2h,腹腔麻醉颈动脉插管取血,分管盛装含药血清,放置备用。大鼠骨髓间质细胞传至6代,分6组诱导培养:常规培养组使用常规培养液(DMEM培养液 体积分数为0.2的胎牛血清 2mmol/L谷氨酸胺)进行培养;肝细胞生长因子诱导组以常规培养液 25μg/L肝细胞生长因子 10-7mol/L地塞米松进行培养;肝细胞生长因子加左归丸组以常规培养液 25μg/L肝细胞生长因子 10-7mol/L地塞米松 10%左归丸含药血清进行培养;条件培养液加对照血清组以常规培养液 50%条件培养液 10%正常大鼠血清进行培养;条件培养液加八珍汤组以常规培养液 50%条件培养液 10%八珍汤含药血清进行培养;条件培养液加左归丸组以常规培养液 50%条件培养液 10%左归丸含药血清进行培养。③实验评估:诱导28d,每组10个复孔,分别于诱导第0,7,14,21,28天免疫细胞化学法检测肝细胞标志物甲胎蛋白、细胞角蛋白18及白蛋白阳性细胞率,PAS染色检测糖原阳性细胞率。结果:①诱导第0天,各组甲胎蛋白、白蛋白阳性细胞呈极少数表达(t=0.44～1.90,P>0.05),细胞角蛋白18及糖原均未见阳性细胞表达。②肝细胞生长因子加左归丸组、条件培养液加左归丸组在诱导第7,14,21,28天白蛋白、细胞角蛋白18、糖原的阳性细胞率均显著高于其他4组(t=5.42～55.00,P<0.05);甲胎蛋白阳性细胞率于诱导第7天时增高显著(t=55.00,P<0.05),此外各时间点又明显降低。③与肝细胞生长因子加左归丸组比较,条件培养液加左归丸组白蛋白阳性细胞率在诱导第14,21,28天时显著升高(t=4.06～7.49,P<0.05);甲胎蛋白阳性细胞率在诱导第7天时显著升高(t=83.69,P<0.05),至诱导第14,21,28天则明显下降(t=55.53～83.00,P<0.05)。结论:左归丸含药血清能够影响骨髓间质细胞向肝系细胞转化过程中的肝细胞标志物,从而提高骨髓间质细胞向肝细胞的转化率。     

组织工程角膜基质的构建

学术背景:角膜供体来源的匮乏及高危角膜移植术后的高排斥率限制了角膜移植的临床应用。构建具有良好生物学活性且能满足一定生理功能要求的组织工程角膜是近年来眼科的研究热点,而角膜基质组织的构建则是利用组织工程技术构建角膜的主要任务、难点和关键所在。目的:总结构建组织工程化角膜基质种子细胞及支架材料的研究进展。检索策略:应用计算机检索Pubmed数据库1980-01/2007-06的相关文献,检索词"cornealstroma;tissueengineering",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1997-01/2007-06期间的相关文章,检索词"组织工程;角膜基质",限定文章语言种类为中文。共检索到59篇文献,对资料进行初审,纳入标准:①与构建组织工程角膜基质密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准:重复性研究。文献评价:文献的来源主要是构建组织工程角膜基质的实验。所选用的30篇文献中,5篇为综述,其余均为临床或基础实验研究。资料综合:①国内角膜盲患者众多,临床上对供体角膜的需求越发迫切。构建具有良好生物学活性且能满足一定生理功能要求的组织工程角膜具有重大的探索价值与临床实际应用意义。②自体或异体角膜基质细胞不仅是最早采用的而且是应用最为广泛的种子细胞。皮肤成纤维细胞应用于构建组织工程角膜基质的文献已见诸于报道。③作为支架材料,胶原、明胶及壳聚糖均有报道用于构建组织工程角膜基质。研究表明人工合成可降解高分子材料聚羟基乙酸材料与角膜基质细胞有较好的亲和力。④随着干细胞研究、材料科学及生物工程学等多学科的发展,组织工程角膜基质的构建越来越凸现其优越性,但它仍然面临许多挑战,比如:如何定向诱导多能干细胞分化为角膜基质细胞;角膜基质支架材料如何改良以保证良好的透明性;支架材料的生物学特性及理化性质需进一步研究。结论:组织工程角膜基质是构建组织工程角膜的重要基础,也预示着临床应用组织工程技术治疗角膜盲时代的到来。它将为解决异体角膜来源匮乏、高危角膜移植成功率低等临床问题提供新的思路。     

Adherent agarose mold cultures: An in vitro platform for multi‐factorial assessment of passaged chondrocyte redifferentiation

Generating the best possible bioengineered cartilage from passaged chondrocytes requires culture condition optimization. In this study, the use of adherent agarose mold (adAM) cultures to support redifferentiation of passaged twice (P2) chondrocytes and serve as a scalable platform to assess the effect of growth factor combinations on proteoglycan accumulation by cells was examined. By 2 days in adAM culture, bovine P2 cells were partially redifferentiated as demonstrated by regression of actin‐based dedifferentiation signalling and fibroblast matrix and contractile gene expression. By day 10, aggrecan and type II collagen gene expression were significantly increased in adAM cultured cells. At day 20, a continuous layer of cartilage tissue was observed. There was no evidence of tissue contraction by P2 cells in adAM cultures. The matrix properties of the resultant tissue as well as proteoglycan 4 (PRG4) secreted by the cells were dependent on the initial cell seeding density. AdAM cultures were scalable and culture within small 3 mm diameter adAM allowed for multi‐factorial assessment of growth factors on proteoglycan accumulation by human P2 chondrocytes. Although there was a patient specific response in proteoglycan accumulation to the various cocktail combinations, the cocktail consisting of 2 ng/ml TGFβ1, 10 ng/ml FGF2, and 250 ng/ml FGF18 resulted in a consistent increase in alcian blue tissue staining. Additional studies will be required to identify the optimal conditions to bioengineer articular cartilage tissue for clinical use. However, the results to date suggest that adAM cultures may be suitable to use for high throughput assessment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2392–2405, 2018.

     

碱性成纤维细胞生长因子对脑出血大鼠神经细胞凋亡的作用

目的:观察碱性成纤维细胞生长因子对大鼠脑出血后神经细胞凋亡的影响。方法:实验于2006-01/07在广西医科大学生理学实验室完成。取成年清洁级Wistar大鼠54只,雌雄各半,体质量250g左右。采用脑内注射胶原酶建立大鼠脑出血模型,动物于苏醒后按Bederson法进行神经病学评分,评分大于3分后入选本实验,入选54只大鼠随机抽签法分为模型组、生理盐水对照组和碱性成纤维细胞生长因子治疗组,每组又分为1,3,7d三个时间点,每组每时间点6只动物,碱性成纤维细胞生长因子治疗组按8μg/kg剂量肌肉注射,1次/d;生理盐水对照组肌肉注射与碱性成纤维细胞生长因子治疗组相同剂量的生理盐水,1次/d;模型组不作任何干预。各组分别于相应时间点取脑组织,然后应用末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末端标记法测定大鼠大脑皮层、海马神经细胞凋亡数目。结果:纳入大鼠54只,均进入结果分析。在建立脑出血模型中共3只死亡,随后对死亡动物进行解剖,发现脑内血肿量过大,致脑疝形成而导致动物死亡,后随机补充动物。①3d时碱性成纤维细胞生长因子治疗组的皮层神经细胞凋亡数比生理盐水对照组少[(38.33±2.94),(45.33±5.35)个,P<0.05]。②7d时碱性成纤维细胞生长因子治疗组的皮层神经细胞凋亡数比生理盐水对照组少[(29.00±5.48),(43.33±8.62)个,P<0.01]。③7d时碱性成纤维细胞生长因子治疗组的海马神经细胞凋亡数比生理盐水对照组少[(19.83±6.85),(28.33±5.72)个,P<0.05]。结论:碱性成纤维细胞生长因子可抑制脑出血后神经细胞凋亡,减少大鼠脑出血后神经细胞的凋亡。     

Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.

Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.     

Awareness,knowledge and self-reported test rates regarding Hepatitis B in Turkish-Dutch: a survey

Background  

Hepatitis B virus infection is an important health problem in the Turkish community in the Netherlands. To prevent transmission and progression of the disease in this community, increased screening is necessary. This study aimed to determine 1) the levels of awareness and knowledge regarding hepatitis B, comparing these in tested and non-tested Turkish-Dutch in Rotterdam; 2) the self-reported hepatitis B test status in this population, and how this is related to demographic characteristics, knowledge and awareness.     

Endoscopic‐assisted transantral‐endonasal approach to large dentigerous cyst of maxillary sinus

Dentigerous cysts are seen in the maxillary canine and third molars. We report a case of dentigerous cysts invading the maxillary sinus, which was managed surgically by endoscopic‐assisted transantral and transnasal approach.     

A review on eating disorders and adolescence

Eating disorders in adolescence are a public health concern with both personal costs and a financial burden for the community health services. This paper is a review of incidence and gender differences of eating disorders; comorbid psychopathology, including substance abuse, mood disorders, anxiety disorders and personality disorders; developmental and intellectual factors; family, socio-cultural functioning and birth order; self-injury and suicidal behaviour with health outcome and therapy success rate. We have also asked several questions from our clinical experience and tried to answer them with our clinical knowledge and based on literature review. Overall, there is an indication that therapy success is significantly correlated with (low) manifestation, specifically for social problems and aggressivity. Due to the complexity of factors involved in the manifestation of eating disorders, the inclusion of cognitive-behavioural therapy as well as family-oriented therapeutic concepts coupled with medical treatment would appear to offer an intervention inventory, which would be most effective in offering adolescents optimal treatment programmes. The implications of our review is discussed in terms of psychotherapeutic treatment plans for adolescents in clinical care.