基质金属蛋白酶-2和血管内皮生长因子在子宫内膜异位症中的表达

目的:探讨MMP-2、VEGF在内异症发生、发展中的作用及相互影响,为内异症的临床诊断和治疗提供科学依据和新思路。方法:SP法检测76例异位内膜、64例在位内膜及72例子宫肌瘤患者(对照组)子宫内膜组织中VEGF、MMP-2的表达。结果:①MMP-2表达异位内膜组强于在位内膜组和对照组;增生期异位内膜组与在位内膜组和对照组之间差异有显著性,分泌期各组内膜之间差异无显著性;正常内膜与在位内膜组分泌期高于增生期,而异位内膜组增生期和分泌期均呈高表达状态。②VEGF表达强度异位内膜组、在位内膜组和对照组依次减弱;增生期异位内膜强于在位内膜和对照组内膜,分泌期异位和在位内膜强于对照组;异位和在位内膜组分泌期强于增生期,对照组增生期和分泌期表达均较弱。③VEGF与MMP-2之间存在正相关关系。结论:MMP-2、VEGF与子宫内膜异位症的发生、发展有关,二者之间存在相互作用。     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Keratin 13基因在喉癌发生中的作用

探讨keratin 13基因在喉癌发生中的作用。方法在keratin 13基因内部及附近选择5个微卫星引物进行LOH分析，于DNA水平间接检测100例喉癌患者中该基因的缺失情况。结果5个STR位点均存在LOH，其中D17S1964E、D17S2092、D17S791、D17S1665及D17S808位点的LOH频率分别为30．48％、26．02％、21．62％、37．66%和21．51％，以D17S1665位点的LOH频率最高，杂合性丢失与临床分期无显著相关。结论Keratin13基因在喉癌的发生中具有重要作用，具体机制有待进一步研究。     

支气管哮喘患者白细胞介素4和白细胞介素13测定的临床意义

目的:探讨血清中白细胞介素4(IL-4)和白细胞介素13(IL-13)在支气管哮喘发病中的作用.方法:本研究对临床确诊的支气管哮喘46例,与正常对照组46例,分别抽取血清采用 ELISA 法测定其 IL-4、IL-13的含量.结果:支气管哮喘急性发作期病人和对照组正常人血清中的 IL-4水平分别为(460.84±27.11)和(132.97±24.66) ng/L,二组经 t 检验后 P＜0.001.两组 IL-13 的水平分别为(23.76±5.44)和(12.61±2.49) ng/L,二组经 t 检验后 P＜0.001.结论:哮喘病人 IL-4、IL-13 明显高于对照组,提示 IL-4、IL-13 对哮喘发病有一定的调控作用,对支气管哮喘气道非特异性炎症和局部免疫反应起重要作用.     

Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.     

Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease

BACKGROUND: Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease. OBJECTIVE: To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared. METHODS: We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years). RESULTS: Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls. CONCLUSION: The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.     

白细胞介素-13功能研究进展

白细胞介素－13主要由活化的Th2(CD4^ )细胞分泌，诱导单核巨噬细胞分化及延长寿命；促进MHC－Ⅱ，CD23表达；抑制炎性和趋化因子产生；诱导B细胞增殖，活化，刺激IgM,IgG的产生和重链的转换；使血管细胞粘附分子－1表达；抑制人类免疫缺陷病毒（HIV）复制；间接诱导巨噬细胞和NK细胞参与抗肿瘤作用。在变态反应性疾病和哮喘中引起呼吸道高反应性，嗜酸粒细胞性炎症，粘液分泌过多，基膜纤维化等，其受体是与IL－4Rα形成功能复合体而发挥作用。IL－13信号转导途径除了JAK／STAT6以外，尚有IRS－1,Fes，磷酸激酶，BCL－6／SOCS等途径。     

New players in old amyloid precursor protein-processing pathways

The amyloid precursor protein (APP) gives rise to beta-amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease (AD) patients. The generation of beta-amyloid peptides requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by neurons and increased BACE1 protein concentrations and enzymatic activities have been reported in the brains of AD patients. However, there is accumulating evidence that, in addition to neurons, reactive astrocytes are capable of expressing BACE1 and, therefore, may contribute to beta-amyloid plaque formation. This suggests that conditions accompanied by chronic astrocyte activation may contribute to developing AD. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG) generation. This led to the hypothesis that classical and novel protein kinase Cs (PKCs), which are activated by DAG/PEs, regulate APP processing. However, in addition to PKCs, there are other DAG/PE receptors present in neurons which may participate in the modulation of APP processing. Munc13-1, a presynaptic protein with an essential role in synaptic vesicle priming, represents such an alternative target of the DAG second messenger pathway. Using Munc13-1 knock-out mice and human neuroblastoma cells transfected with wild-type and mutant Munc13-1 constructs it was demonstrated that Munc13-1 acts independently of and in parallel with PKC to modulate APP metabolism. Therefore, agonists specific for the Munc13-1 C1-domain or small molecules mimicking the function of the endogenous Munc13-1 activator RIM1 may prove useful to shift APP processing towards the non-amyloidogenic pathway.     

半乳糖凝集素PPL13在人胎盘血管内皮细胞中表达的实验研究

目的：以原位杂交法检测PPL13在人胎盘组织的表达情况。方法：用DIG标记的PPL13有义RNA探针及反义RNA探针与胎盘组织切片进行原位杂交。结果：反义RNA探针杂交标本显色3h，显微镜下可见胎盘毛细血管内皮细胞中出现棕色沉淀物，滋养层细胞中未见棕色沉淀物；而有义RNA探针杂交标本显色24h仍无棕色沉淀物出现。结论：PPL13在人胎盘内皮细胞中特异性表达．提示PPL13可能与胎盘的屏障作用有关。     

人脑胶质瘤白介素13受体基因表达与肿瘤增殖活性的关系研究

目的探讨人脑胶质瘤白介素13受体（IL-13R）基因表达与肿瘤增殖活性的关系。方法对6例正常脑组织，50例人脑胶质瘤和2个脑瘤体外细胞系采用RT—PCR法和免疫组织化学法检测IL-13R。结果人脑胶质瘤组织IL-13RαmRNA总阳性表达率70％，正常脑组织中仅1例有极弱的表达；2例恶性胶质瘤体外细胞系均高表达。IL-13RαmRNA表达率和表达丰度与胶质瘤分级（前者rs=0．87，P〈0．01；后者rs=0．69，P〈0．01）、肿瘤增殖活性Ki-67LI（r=0．64，P〈0．01）呈正相关，即胶质瘤恶性程度越高，IL-13RαmRNA表达率和表达水平越高。结论IL-13Rα基因在人脑胶质瘤中表达上升，与肿瘤的分级和肿瘤增殖活性呈正相关，可作为预测某些肿瘤治疗效果及监测复发的指标之一。