IL-4与IL-10联合诱导异种骨移植免疫耐受的体外研究

目的　探讨 IL - 4和 IL - 10在诱导异种骨移植免疫耐受中的作用。方法　反应细胞为 BAL B/c小鼠脾淋巴细胞 ,刺激细胞为新西兰白兔血淋巴细胞 ,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入 IL - 4、IL - 10及两者联合应用 ,通过测定其 3H- Td R掺入率 ,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果　无论在细胞刺激组还是骨上清液刺激组 ,IL- 4对淋巴细胞增殖均有显著抑制作用 (P<0 .0 0 1和 P<0 .0 5 ) ,IL- 10未表现出抑制作用 (P>0 .0 5 )。在两组 IL- 4和 IL - 10联合应用均产生比 IL - 4单独应用更为明显的细胞增殖抑制作用 (P<0 .0 0 1和 P<0 .0 5 )。结论　 IL - 4对由细胞或骨上清液刺激产生的淋巴细胞增殖均有很好的抑制作用 ,IL- 10没有表现出抑制作用 ;IL- 4与 IL- 10联合应用有协同抑制作用。     

Distinct osteogenic mechanisms of bones of distinct origins

Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

Th2细胞因子调节哮喘炎症细胞转运机制的研究

目的 探讨Th2细胞因子IL-5、IL-13调节哮喘炎症过程中肺和骨髓之间的细胞转运机制。方法 建立哮喘动物模型,获取肺泡灌洗液,检测IL-5、IFN-γ,浓度并进行病理分析;应用原位杂交技术检测肺组织IL-5、IL-13 mRNA表达和骨髓IL-5mRNA表达;免疫组化法观察肺、骨髓IL-5免疫反应细胞;流式细胞仪检测骨髓CD34、CD3阳性细胞。结果 哮喘组肺泡灌洗液IL-5浓度明显高于对照组(P<0.001);哮喘组肺组织病理改变显示小气道痉挛,管壁周围炎性细胞浸润,以嗜酸粒细胞、淋巴细胞为主;哮喘组肺组织IL-5、IL-13 mRNA表达较对照组显著增加(P<0.01);哮喘组骨髓IL-5 mRNA阳性细胞明显增加(P<0.001),与肺组织IL-5 mRNA表达的增高密切相关(P<0.05);此外,哮喘组肺组织和骨髓IL-5免疫反应细胞显著增加(P<0.01),骨髓CD34、CD3细胞均显著增高(P<0.01),并且CD34增高与骨髓细胞表达IL-5 mRNA密切相关(P<0.05)。结论IL-5可能在转录和转录后水平均参与调节骨髓嗜酸粒细胞的功能和炎症细胞在肺和骨髓之间的转运。     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.     

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.     

神经化组织工程骨构建的初步观察

目的评估两种组织工程骨体内神经化重建方法的成骨效果,研究神经化与成骨的相互关系。方法26只新西兰大白兔,其中24只随机分成四组:组织工程骨组(A组),感觉神经束植入组(B组),运动神经束植入组(C组),血管束植入组(D组);另2只为空白对照组。每只动物均制备左侧股骨长1.5cm的段缺性骨与骨膜缺损,钢板固定后骨缺损处分别植入用四种方法制备的组织工程骨。植入的神经分别是隐神经和股神经肌支。术后4、8、12周摄股骨正位X线片,用放射影像学评分和X线阻射影分析比较骨缺损修复情况。结果在组织工程骨中植入感觉神经束后,比单纯组织工程骨和运动神经束植入的修复效果均有明显提高,而在组织工程骨中植入运动神经束与单纯组织工程骨修复骨缺损的效果相比较无明显差异,感觉神经束植入与血管束植入的成骨效果比较无明显差异,血管束植入组的成骨效果优于其它两组。结论利用感觉神经束植入的方法可以提高组织工程骨的成骨作用,而植入运动神经束却无此作用。     

同种异体骨与自体骨移植治疗青少年脊柱侧凸的比较研究

[目的]观察同种异体骨移植与自体骨移植治疗青少年脊柱侧凸的临床效果.[方法]对1996～2006年本科收治的63例青少年脊柱侧凸患者的临床资料,采用回顾性"病例-对照"研究方法进行分析,A组(同种异体骨移植组)32例,10～15岁,平均12.2岁;Cobb's角38°～113°,平均62°;B组(自体髂骨移植组)31例,年龄9～14岁,平均12.4岁;Cobb's角41°～105°,平均54°.所有患者均选择中华长城椎弓根内固定系统经后路矫正,术后定期随访并对临床效果进行评估.[结果]出院后2个月即开始随访,随访时间18～24个月,平均26个月;亦无严重并发症发生;A组的手术时间、失血量较B组患者减少,组间具有统计学意义(P＜0.01).[结论]两组患者具有相似的临床效果,在严格掌握适应证,充分术前准备、正确手术操作、及时术后处理的前提下,同种异体骨移植能够有效替代自体髂骨移植治疗青少年脊柱侧凸.