Angiogenesis in rheumatoid arthritis: a disease specific process or a common response to chronic inflammation?

Angiogenesis is the formation of new blood vessels from existing vessels. During RA new blood vessels can maintain the chronic inflammatory state by transporting inflammatory cells to the site of inflammation and supplying nutrients and oxygen to the proliferating inflamed tissue. The increased endothelial surface area also creates an enormous capacity for the production of cytokines, adhesion molecules, and other inflammatory stimuli, simultaneously the propagation of new vessels in the synovial membrane allows the invasion of this tissue supporting the active infiltration of synovial membrane into cartilage and resulting in erosions and destruction of the cartilage. This angiogenic phenotype is promoted by several pro-angiogenic molecules, the most potent of which is vascular endothelial growth factor (VEGF). Although angiogenesis is recognized as a key event in the formation and maintenance the infiltration of synovial membrane during RA, it is unclear whether angiogenesis should be considered a specific feature of the disease or a common inflammation driven process. However the emergence of biological therapies, such as anti TNF blockade, has suggested that there are features of the inflammatory response that are not general but contextual to the specificity of the tissue where inflammation occurs, and point out the relevant role of tissue-resident stromal cells in determining the site at which inflammation occurs and the specific features of chronic inflammation such as that occurs in RA.     

CTLA4Ig基因修饰BMSCs对异种胰岛移植排斥反应的影响

目的 探讨细胞毒性T淋巴细胞相关抗原4免疫球蛋白( CTLA4Ig)基因修饰骨髓间充质干细胞(BMSCs)在异种胰岛移植排斥反应中的作用.方法 构建携带CTLA4Ig基因的重组腺病毒载体,用其感染BMSCs并和人胰岛细胞移植到糖尿病大鼠肾包膜下,建立人-大鼠异种胰岛移植模型.观察胰岛移植后糖尿病大鼠血糖变化、生存情况以...     

可移植性Balb/c小鼠急性红白血病动物模型的建立

目的建立稳定的可移植性Balb/c小鼠的急性红白血病动物模型。方法将2×106个的EL9611红白血病细胞通过尾静脉输注每只Balb/c(H-2d)小鼠(n=10),体内传代建立EL9611红白血病动物模型,通过15代的连续传代观察模型的可靠性,以健康BALB/c鼠(n=4)作为正常对照。观察小鼠腹部、肝脾重量,计数实验组和正常对照组的外周血白细胞数,取发病晚期小鼠的外周血涂片行Giemsa染色观察,肝脾组织经10%甲醛固定、石蜡切片、HE染色检查,计算小鼠平均生存时间、发病率和死亡率。结果接种2×106个EL9611白血病细胞后实验组平均生存时间(MST)为(14.5±2.1)d,生存时间与正常对照组相比,P<0.01,经15代的连续传代,未见自发缓解,发病率和死亡率均为100%,无性别选择性,发病晚期小鼠出现肝脾肿大和外周血WBC升高等典型白血病的表现,死亡时肝重(2.40±0.48)g,脾重(0.84±0.20)g,与正常对照组相比,P<0.01,死亡前外周血WBC计数为(3.33±0.27)×107/mL,与正常对照组比,P<0.05,外周血中可见多量异形白血病细胞,病理检查示肝脾正常组织结构破坏,大量白血病细胞浸润。结论采用EL9611红白血病细胞2×106静脉输注体内传代的方式可建立起稳定的可移植性Balb/c小鼠的急性红白血病动物模型。     

EL9611红白血病小鼠急性GVHD动物模型的建立

目的: 建立EL9611红白血病小鼠急性移植物抗宿主病(GVHD)的动物模型。方法: 同种异基因骨髓移植(allo-BMT)以C57BL/6(H-2^b)鼠为供鼠,BALB/c(H-2^d)为受鼠。设白血病组(n=10)、照射对照组(白血病鼠照射后不进行allo-BMT,n=4)、GVHD组(白血病鼠照射+allo-BMT,n=10)及正常对照组(n=4)。白血病组采用每只BALB/c鼠尾静脉输注2×10⁶个EL9611红白血病细胞建立红白血病动物模型;GVHD组于接种白血病细胞7 d后行总剂量为8.0 Gy的1次性 γ射线全身照射(TBI),照射后5 h内每只小鼠尾静脉输注C57BL/6鼠骨髓细胞2×10⁶个＋脾细胞1×10⁷个,建立EL9611红白血病小鼠的急性GVHD动物模型。观察小鼠体位、皮毛、大便等临床表现,病理检查肝脾、皮肤、小肠、外周血和骨髓,计算生存率。结果: 白血病组生存时间(14.5±2.1) d ,生存时间与GVHD组相比P<0.01,死亡率100％,无自发缓解,死亡时肝脾肿大(肝重2.40 g±0.48 g,脾重0.84 g±0.20 g,与正常对照组比P<0.01),外周血WBC升高 ,病理检查示组织正常结构破坏,白血病细胞浸润。照射对照组生存时间为(9.0±0.7) d,生存时间与GVHD组和正常对照组相比差异显著(P<0.01),死亡率100％,病理检查显示造血衰竭。GVHD组生存时间为(32.0±3.2)d,生存时间与其它各组相比P<0.01,死亡率100％,allo-BMT后第10-13 d出现症状,临床表现和病理检查符合Ⅰ到Ⅱ度GVHD的改变。结论: 采用EL9611红白血病细胞(2×10⁶/鼠)静脉输注的方式可成功建立EL9611红白血病动物模型;接种EL9611红白血病细胞第7 d行TBI +allo-BMT可成功建立EL9611红白血病小鼠的急性GVHD动物模型。     

内蒙古地区慢性粒细胞白血病患者HLA-DRB1基因多态性的研究

目的为研究内蒙地区汉族人群人类白细胞抗原（human leukocyte antigen,HLA）DRB1基因与CML白血病的相关性。方法采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交（flow cytometry-sequence specific oligonucle-otide probe,FLOW-SSOP）方法对内蒙地区39例慢性粒细胞白血病chronic myeloid leukemia,CML）患者HLA-DRB1等位基因多态性进行分析,以北方地区健康群体资料作为正常对照。结果在HLA-DRB1等位基因中,CML白血病组中DRB1＊1001,＊16XX等位基因频率高于对照组（0.593%,0.603%,P〈0.05）。结论 DRB1＊1001,DRB1＊16XX等位基因与CML相关联,可能是易感基因。     

Developmental assessment of preterm and term children at 18 months: reproducibility and validity of a postal questionnaire to parents

AIM: To examine the degree of agreement between the paediatrician's assessment and parental reporting of infants' development using a postal questionnaire. METHODS: The developmental status of 241 infants in the charge of 9 community paediatricians or discharged from one Neonatal Intensive Care Unit (NICU) was assessed by their parents 18 mo after delivery, using a postal questionnaire regarding child's height, weight. respiratory, hearing and vision problems, and items taken mainly from the Griffiths' Developmental Scales. At this age, infants were seen by the community or NICU paediatricians, for a complete physical and neurodevelopmental examination. RESULTS: The mean agreement on items regarding developmental areas between parents and paediatricians was 93.0%. In general, parents and professionals agreed on items describing gross motor behaviour (k from 0.39 to 0.83) and disagreed on individual questions describing language/relational behaviour (k from 0 to 0.38). A 97.9% level of agreement was found for hearing status (k = 0), and 96.2% for assessment of vision (k = 0.29), whereas the level of agreement ranged from 43.2% to 86.2% (k from 0 to 0.15) for the three questions describing respiratory problems. The mean weight and height assessments by paediatricians and parents of infants at 18 mo of age were similar. CONCLUSIONS: Further improvement of the questionnaire is needed, but our findings suggest that this methodology can be considered for use in comparing large cohorts of infants included in randomized clinical trials.     

Interleukin (IL)‐17‐producing pathogenic T lymphocytes co‐express CD20 and are depleted by rituximab in primary Sjögren's syndrome: a pilot study

Compelling evidence suggests that interleukin (IL)‐17 and IL‐17‐producing cells play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS). We investigated phenotypical and functional effects of the anti‐CD20 antibody rituximab (RTX) on circulating and glandular IL‐17‐producing T cells in pSS. RTX is able to deplete glandular IL‐17⁺ CD3⁺CD4^–CD8^– double‐negative (DN) and CD4⁺ Th17 cells as well as circulating IL‐17⁺ DN T cells. A fraction of glandular and circulating IL‐17⁺ DN cells and CD4⁺ T helper type 17 (Th17) cells co‐expresses CD20 on the cell surface explaining, at least in part, such depletive capacity of RTX. The exposure to RTX does not rescue the in‐vitro corticosteroid resistance of IL‐17⁺ DN T cells. Our results support further the therapeutic role in pSS of RTX that, despite its B cell specificity, appears able to also hamper IL‐17‐producing T cells in this disease.     

H‐ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Macrophage activation syndrome (MAS) is hyperinflammatory life‐threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H‐/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H‐ferritin and L‐ferritin; (ii) CD68⁺/H‐ferritin⁺ and CD68⁺/L‐ferritin⁺; and (iii) interleukin (IL)‐1β, tumour necrosis factor (TNF) and interferon (IFN)‐γ. We also explored possible correlations of these results with clinical data. H‐ferritin, IL‐1β, TNF and IFN‐γ were increased significantly in MAS. Furthermore, an increased number of CD68⁺/H‐ferritin⁺ cells and an infiltrate of cells co‐expressing H‐ferritin and IL‐12, suggesting an infiltrate of M1 macrophages, were observed. H‐ferritin levels and CD68⁺/H‐ferritin⁺ cells were correlated with haematological involvement of the disease, serum ferritin and C‐reactive protein. L‐ferritin and CD68⁺/L‐ferritin⁺ cells did not correlate with these parameters. In conclusion, during MAS, H‐ferritin, CD68⁺/H‐ferritin⁺ cells and proinflammatory cytokines were increased significantly in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H‐ferritin and CD68⁺/H‐ferritin⁺ were associated significantly with haematological involvement of the disease, suggesting biomarkers assessing severity of clinical picture.     

Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians