Mononuclear cells in glomeruli and cytokines in urine reflect the severity of experimental proliferative immune complex glomerulonephritis.

Immunohistochemical methods were used to investigate the role of macrophages in the progression of proliferative immune complex glomerulonephritis. The mononuclear cell component of glomerular inflammation was analysed in three different stages of chronic serum sickness, each of which was clearly distinguished by criteria of kidney function. Urinary excretion of the macrophage secretory products interleukin-1 and tumour necrosis factor was also evaluated in relation to the functional severity of kidney disease. T lymphocytes and macrophages began to accumulate in glomeruli at the onset of proteinuria, but not before. Urinary excretion of interleukin-1 also began with proteinuria. Proteinuria increased in direct correlation with increases in the number of glomerular macrophages. Development of the most severe stage of glomerulonephritis, characterized by cachexia, declining kidney function, and necrotizing glomerular pathology, was accompanied by the disappearance of T cells from glomeruli and the expression of highly abnormal phenotypes by most macrophages. In addition, there was a switch from urinary excretion of interleukin-1 to excretion of tumour necrosis factor. The progression of proliferative immune complex glomerulonephritis was associated with qualitative as well as quantitative changes in glomerular macrophage populations. Differentiation and/or activation of those glomerular macrophages may have resulted from local T cell-mediated immunoregulation. Measurements of urinary cytokine excretion provided a reliable means of monitoring disease progression. The local action of tumour necrosis factor probably contributed to declining kidney function in the most severe stage of disease.     

Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis

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Production of transforming growth factor-beta 1 (TGF-beta1) by blood monocytes from patients with different clinical forms of leprosy

In the present study, the concentration of TGF-beta1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (PBMC) and either stimulated with PGL-1 or lipopolysaccharide (LPS) or left unstimulated was determined by ELISA. The cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. The adherent cells exhibited spontaneous release of TGF-beta1 in all clinical forms of leprosy and in healthy individuals; however, lepromatous leprosy/borderline leprosy (LL/BL) patients presenting erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-beta1 than either the other patients studied or the controls. These high TGF-beta1 levels were consistently observed when LL/BL ENL cells were stimulated with phenolic glycolipid (PGL-1) or LPS, and even in the absence of a stimulus (P < 0.01). The most significant differences in TGF-beta1 levels were observed when comparing the results in the presence of PGL-1 from ENL with, in order of significance: tuberculoid leprosy (TT) patients (P < 0.001), LL/BL patients without ENL (P < 0.01), healthy individuals (P < 0.01) and borderline-borderline/borderline-tuberculoid (BB/BT) patients with reversal reaction (RR) (P < 0.01). The BB/BT patients produced equivalent levels of TGF-beta1 compared with LL/BL patients without ENL, for all types of stimuli (P > 0.05). In contrast, TT patients produced the lowest levels of TGF-beta1 among all the subjects studied (both patients and healthy controls), especially following PGL-1 stimulation (P < 0.001, and P < 0.05, respectively). In conjunction with our previous data regarding TGF-beta1 expression in dermal lesions, it appears that TGF-beta1 probably plays different roles in leprosy: (i) to mediate a suppressive action locally, associated with the presence of PGL-1, and (ii) to induce proinflammatory effects when secreted systemically by monocytes, thereby acting as a modulatory cytokine in the acute inflammatory reactions of ENL and associated with the Th2 immune response in multibacillary forms of leprosy.     

Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients.

Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti-Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.     

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.     

The Emergence and Functional Fitness of Memory CD4+ T Cells Require the Transcription Factor Thpok

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乳腺癌肿瘤标志物阳性率的相关因素分析

目的:研究肿瘤标志物CEA、CA125、CA15-3在乳腺癌中的诊断价值,对影响肿瘤标志物阳性率的相关因素进行分析.方法:收集111例手术病理确诊为乳腺癌患者,研究各个肿瘤标志物的阳性率,并就患者的发病年龄、月经状态、病变部位、皮肤桔皮样改变、肿块大小、淋巴结转移情况、远处转移、分期、病理类型、ER、PR、c-erbB-2、P53和BCL-2等共14项因素与肿瘤标志物阳性率的相关情况进行单因素方差分析和logistic回归模型.结果:CEA、CA125、CA15-3和联检的阳性率分别为10.1%、10.8%、9.1%和13.8%.单因素分析和多因素分析均显示与乳腺癌肿瘤标志物阳性率显著相关的因素有:肿瘤分期(χ2=17.258,P=0.001)、皮肤改变(χ2=9.923,P=0.002)、远处转移(χ2=7.28,P=0.007).单因素分析显示P53显著相关(χ2=10.45,P=0.005),但多因素分析显示无统计学意义(wald χ2=1.334,P=0.248).其余因素两个分析的结果均显示无统计学意义.结论:联检可以提高乳腺癌肿瘤标志物阳性率.肿瘤分期、皮肤改变和远处转移与肿瘤标志物阳性率显著相关,P53的相关性有待进一步研究.     

大鼠下颌下腺内自分泌运动因子及其受体的定位

目的:探讨自分泌运动因子及其受体在大鼠下颌下腺中的表达特点,为进一步研究自分泌运动因子及其受体对下颌下腺是否有功能意义提供依据。方法:应用HE和免疫组织化学SABC法染色。结果:大鼠下颌下腺颗粒曲管、纹状管及小叶间导管上皮细胞呈自分泌运动因子及其受体免疫反应阳性。免疫反应产物分布于胞质,胞核为免疫反应阴性。下颌下腺的腺泡上皮细胞均呈自分泌运动因子及其受体免疫反应阴性。结论:正常大鼠下颌下腺仅导管上皮有自分泌运动因子及其受体的分布,提示下颌下腺产生的自分泌运动因子对下颌下腺及机体可能有重要调节意义。     

健脾补肾药对脾虚大鼠细胞因子水平的影响

目的 :观察健脾补肾方药对实验性脾虚证大鼠细胞因子的影响 ,探讨脾虚证与细胞因子的关系及脏腑相关的意义。方法 :选用SD雄性大鼠 ,随机分为 :正常对照组 ,脾虚模型组 ,健脾补肾方高、低剂量组 ,通过大黄复制脾虚证动物模型 ,并用健脾补肾方药进行防治。采用放射免疫分析观察各组动物血清肿瘤坏死因子(TNF)、白细胞介素 - 6 (IL - 6 )、白细胞介素 - 2 (IL - 2 )水平的变化。结果 :脾虚模型组大鼠血清TNF、IL - 6、IL - 2含量均比正常对照组显著降低 (p <0 0 1) ,而健脾补肾方药能明显升高TNF、IL - 6、IL - 2含量 ,使体重增加 ,脾脏和胸腺组织的重量增加。结论 :脾虚证的发生与细胞因子网络调节系统的失衡有关 ,而健脾补肾中药对实验性脾虚证有较好的防治作用 ,脾肾相关理论对实践有指导意义。     

NGF在成年猴脑的分布

为了解NGF在成年猴脑的分布,采用免疫组化SP法对成年猴脑多个冠状位切片进行免疫组化反应。结果证明,NGF阳性反应神经元主要分布于大脑皮质Ⅲ、V层,小脑Purkinje细胞,海马,齿状回,纹状体,脑干网状结构等处。此外,在黑质、舌下神经核、迷走神经背核、前庭神经核、三叉神经核、疑核、下橄榄核也出现NGF阳性反应。在大脑和脑干还观察到NGF阳性胶质细胞。本实验结果表明,在成年猴脑的多个脑区有NGF表达,提示NGF可能涉及猴脑某些神经元及胶质细胞的生理过程。