Severe asthma in children

Most children with asthma have their disease easily controlled if low‐dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high‐dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed. First, the diagnosis of asthma should be confirmed, then co‐morbidities assessed. Next, a nurse‐led assessment further characterizes the problem, conventionally categorizing the child as either having difficult asthma or severe therapy‐resistant asthma. Here, we reassess in particular the interactions between, and management of, these two categories, highlighting that this dichotomous classification may need reconsideration. We use bronchoscopy and an intramuscular steroid injection to determine if the child has steroid‐resistant asthma, using a novel, multidomain approach because the adult definition does not apply to around half the children we see. Finally, we highlight some mechanistic data which have emerged from this protocol such as the absence of T‐helper 2 (TH2) cytokines even in eosinophilic severe asthma and the potential role of the innate epithelial cytokine IL‐33, novel data on lineage negative innate lymphoid cells, which we can measure in induced sputum, and demonstrating that intraepithelial neutrophils are associated with better, not worse asthma outcomes. Severe paediatric asthma is very different from severe asthma in adults, and approaches must not be uncritically extrapolated from adult disease to children.     

三氧化矿物凝聚体对牙乳头细胞增殖和分化影响的实验研究

目的 研究不同质量浓度的三氧化矿物凝聚体(mineral trioxide aggregate,MTA)对大鼠牙乳头细胞(rat dental papilla cells,RDPC)增殖和分化能力的影响,探讨MTA在根尖诱导方面的作用.方法 组织块法原代培养RDPC并鉴定.制备不同质量浓度的MTA浸提液(0.002、0.02、0.2、2及20 g/L)并处理第3代RDPC 3 d,以普通培养液的RDPC作为空白对照组(每组6孔),用甲基噻唑基四唑(methyl thiazolyl tetrazolium,MTT)比色法检测细胞增殖能力,筛选最适合细胞生长的质量浓度.用0.002 g/L MTA培养RDPC,以普通培养液的RDPC作为空白对照组,检测1、3、5、7 d RDPC的碱性磷酸酶(alkaline phosphatase,ALP)活性和1、3、5 d RDPC的Ⅰ型胶原含量.用方差分析对不同浓度MTA干预后RDPC的增殖能力进行统计学分析,用t检验对0.002 g/L MTA干预后RDPC分泌的ALP活性和Ⅰ型胶原含量进行统计学分析.结果 MTT法检测不同质量浓度MTA对RDPC增殖能力影响中,培养3d后的A值20 g/L组(0.092±0.011)显著低于空白对照组(0.249±0.006),差异有统计学意义(P＜0.01)；0.02和0.002 g/L组的A值(分别为0.267±0.005、0.276±0.006)均显著高于空白对照组(0.249±0.006),差异均有统计学意义(P＜0.01).ALP活性检测结果显示,MTA组3、5、7d的A值[分别为(0.217 ±0.008)、(0.253±0.005)和(0.279±0.004)]均显著高于空白对照组相应时间点的A值[分别为(0.166±0.006)、(0.221±0.006)、(0.242±0.004)],差异均有统计学意义(P＜0.01).3、5d的Ⅰ型胶原含量MTA组[分别为(78.46±2.72)、(90.73±3.08) μg/L]均显著高于相应时间点的空白对照组[分别为(66.75±3.08)、(74.27±3.50) μg/L],差异均有统计学意义(P＜0.01).结论 高浓度的MTA抑制RDPC的生长,低浓度的MTA可以促进RDPC的增殖和分化.     

The thymus in autoimmune Myasthenia Gravis: Paradigm for a tertiary lymphoid organ

In autoimmune Myasthenia Gravis (MG), a neuromuscular disease generally mediated by autoantibodies against the acetylcholine receptor (AChR), the muscle is the target organ of the autoimmune attack, while the thymus seems to be the primary production site of the autoantibodies. In the majority of patients with anti-AChR antibodies, it is characterized by the presence of germinal centers, which contain B cells that produce anti-AChR antibodies. In this review, we summarize recent results regarding neoangiogenic processes, cell infiltration and modified chemokine expression in the MG thymus, which are typical features of secondary lymphoid organs. The structural and functional changes in the MG thymus therefore allow us to declare it to be an archetype for tertiary lymphoid neogenesis providing optimal settings for the interaction between lymphocytes and antigen presenting cells in order to elicit an immune response. We further discuss factors that may have a key role in the transformation of the MG thymus into a tertiary lymphoid organ, such as IFN type I and dsRNA signaling. These factors could also be of importance in other autoimmune diseases, especially those characterized by tertiary lymphoid neogenesis.     

Biological evaluation of a new pulp capping material developed from Portland cement

This study evaluates the biological properties of a new pulp capping material developed from Portland cement. This study was conducted on 48 teeth in 4 dogs (12 teeth/dog). The dogs were classified into two equal groups (n = 24 teeth) according to the evaluation period including: group A (3 weeks) and group B (3 months). Each group was further subdivided into three equal subgroups (n = 8 teeth) according to the capping material including: subgroup 1: mineral trioxide aggregate (MTA), subgroup2: Portland cement + 10% calcium hydroxide + 20% bismuth oxide (Port Cal) and subgroup 3: Portland cement + bismuth oxide. After general anesthesia, a class V buccal cavity was prepared coronal to the gingival margin. After pulp exposure and hemostasis,the capping materials and glass ionomer filling were placed on the exposure sites. All histopathological findings, inflammatory cell count and dentin bridge formation were recorded. Data were analyzed statistically. After 3 months, the histopathological picture of the pulp in subgroup 1 showed normal pulp, continuous odontoblastic layer and complete dentin bridge formation while subgroup 2 showed partial and complete dentin bridge over a normal and necrotic pulps. Subgroup 3 showed loss of normal architecture, areas of necrosis, complete, or incomplete dentin bridge formation, attached and detached pulp stones and fatty degeneration in group B. For group A, MTA subgroup showed the least number of inflammatory cell infiltrate followed by Port Cal subgroup. While subgroup 3 showed the highest number of inflammatory cell infiltrate. For group B, the mean inflammatory cell count increased with the three tested materials with no statistical difference. Regarding dentin bridge formation at group A, no significant differences was found between subgroups, while at group B, MTA subgroup exhibited significantly higher scores than other subgroups. In conclusion, addition of calcium hydroxide to Portland cement improves the dentin bridge formation qualitatively and quantitatively.     

Ultrastructural study of M cells from colonic lymphoid nodules obtained by colonoscopic biopsy

The present study was undertaken to investigate ultrastructurally the epithelium covering lymphoid nodules obtained from colonoscopic biopsies of the human colon and rectum. Colonoscopy using the dye spraying contrast, method was performed in nine patients who showed x-ray evidence of lymphonodular hyperplasia. Fifty-two colonoscopical biopsy specimens, of lymphoid nodules were obtained from the ascending, transverse, and descending colon and rectosigmoid region. All specimens were observed by light and electron microscopy. Light microscopy disclosed large lymphoid follicles protruding into the lumen with a dome-type configuration. These extended to the lamina propria of the mucosa and were associated with a massive lymphoid aggregation extending as far as the muscularis mucosa from the submucosa. The epithelium covering these nodules contained a few goblet cells and many lymphocytes. Observation of the elevated surface at the apex by scanning electron microscopy revealed M cells with sparse microvilli in the dome epithelium surrounded by crypts. Transmission electron microscopy disclosed M cells enfolding many immature or mature lymphocytes and plasmocytes. The M cells had cytoplasmic microvilli (so-called microfolds) on their surfaces, well-developed tubulovesicular systems, and vacuoles in the cytoplasm. The basic structure of the M cells as observed by scanning and transmission electron microscopy was the same as that of M cells in the Peyer's patches of humans and mice. The apical surface of the colonic lymphoid follicles in Crohn's disease patients was associated with erosions observed by scanning electron microscopy. The erosions proved to be the naked surface of the dome after removal of the epithelium and many holes from 2.0 to 6.0 m in diameter were observed on the naked surface. At high magnification, lymphocytes were seen projecting from holes (18%) on the naked surface of the dome. These ultrastructural findings indicate that human colonic lymphoid follicles are very similar to those seen in other species.     

固有淋巴细胞研究进展

长期以来,自然杀伤(NK)细胞被认为是固有免疫系统中唯一属于淋巴谱系的细胞群体,然而近来研究揭示人和小鼠体内存在着多种类型的固有淋巴细胞(ILC)。这些新发现的ILC群体主要分布于黏膜屏障部位,尽管数量较少,但在抵抗病原体入侵和维持组织器官稳态等方面发挥重要作用。ILC发育分化早期存在着共同前体,但在后期阶段受不同转录因子调控,成为表型和功能不同的ILC成员。不同ILC亚群有着不同的细胞因子分泌谱,依据辅助性T细胞亚群的分类方法,ILC家族可以分成三类。ILC多样性的发现极大地丰富了固有免疫的内涵,也为我们研究固有免疫和适应性免疫之间的联系开辟了新途径。     

肺原发性非霍奇金淋巴瘤28例临床病理分析

目的：探讨肺原发性非霍奇金淋巴瘤( primary non-Hodgkin lymphoma, PNHL)的临床病理学特征。方法回顾性分析28例肺PNHL临床表现、影像学和病理学特征,并复习相关文献。结果28例肺PNHL中,男性18例,女性10例,年龄27~82岁,中位年龄57岁。28例均为非霍奇金淋巴瘤( non-Hodgkin lymphoma, NHL),其中黏膜相关淋巴组织结外边缘区淋巴瘤17例,弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma, DLBLC)5例,NK/T细胞淋巴瘤2例,间变性大细胞淋巴瘤(ana-plastic large cell lymphoma, ALCL)2例,套细胞淋巴瘤(mantle cell lymphoma, MCL)及外周T细胞淋巴瘤,非特指各1例。1/3肺PNHL患者无特异性临床症状,主要表现为咳嗽、胸痛、呼吸困难和乏力等。影像学检查多数表现为单肺或双肺阴影,孤立或多发结节,并可累及气管或支气管。随访16例,时间3~38个月,3例患者行肺叶切除术(2例术后辅助化疗),7例行单纯化疗,5例未行任何治疗。13例生存,2例死亡,1例术后2年出现左侧腹股沟淋巴结转移。结论肺PNHL的临床和影像学无特异性改变,以黏膜相关淋巴组织结外边缘区淋巴瘤最常见,其他少见的高度侵袭性淋巴瘤也可发生。确诊需依赖病理检查,免疫组化及分子病理学检测有助于该类型淋巴瘤的诊断。     

Regression of atypical lymphoid hyperplasia after eradication ofHelicobacter pylori

A rare case of endescopic and histological regression of a gastric lymphoid mucosal lesion after eradication ofHelicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence ofH. pylori infection. Successful eradication ofH. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication ofH. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be establisted.     

Peyer's Patches Epithelium in the Rat

The epithelial layer covering lymphoid follicles of Peyer's patches consists of cells with a different surface morphology. Some of these cells have been described as a distinct cytotype, the so-called M cells. In order to resolve the controversy on the specific morphological and biochemical markers of M cells, structural, ultrastructural, and morphometrical study of the epithelium covering the rat Peyer's patches were performed. Peyer's patches from healthy rats were processed for light microscopy, immunohistochemistry, in situ nick-end labeling (TUNEL), and scanning and transmission electron microscopy. A morphometric study was also performed to evaluate microvillus density, length, and number of lysosomes in different areas of the epithelium. Peyer's patches were covered by simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large number of enterocytes were observed. Ultrastructural observations revealed that the DE showed cells with different morphology. The density and length of microvilli and the lysosome number varied along the whole dome without significant differences. The DE cells characterized by short and disorganized microvilli appeared always in close spatial relationship with lymphocytes. In conclusion, the concept that distinct cell types (enterocytes and M cells) can be identified in the rat DE does not appear to be valid based on morphological criteria. It seems correct to consider that in rat Peyer's patches the presence of scarce goblet cells and a large number of enterocytes showing dynamic morphofunctional modifications is related to the functional state and/or to cell cycle.     

Lymphocyte ‘homing’ and chronic inflammation

Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV‐like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV‐like vessel‐mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.