酪氨酸激酶抑制剂对气管上皮细胞生长的影响

目的探讨酪氨酸激酶抑制剂(Tyrosine kinase inhibitor,TKI)对培养气管上皮细胞生长的影响.方法通过MMT法、3H-胸腺嘧啶(3H-TdR)掺入法及流式细胞计数,观察3种TKIs:Tyrphostin AG1478、Genistein(Sigma)及金转停对原代培养的大鼠气管上皮细胞增殖、周期及凋亡的影响,以及TKIs对表皮生长因子(EGF)的阻断作用.结果MTT法显示3种TKI均对气管上皮细胞的生长具有时间和剂量依赖性抑制作用,同时,TKI阻断EGF对气管上皮细胞生长的刺激作用,3种TKIs的作用无明显差异;1μmol/L的Tyrphostin AG1478、Genistein及金转停分别使气管上皮细胞的TdR掺入率降低18.3%、20.9%及19.7%,与MTT比色法结果一致.同时,Tyrphostin AG1478不仅加速气管上皮细胞的凋亡而且阻止细胞有丝分裂.TKIs可阻断表皮生长因子(EGF)对气管上皮细胞生长的刺激作用.结论TKIs不仅抑制对原代培养的大鼠气管上皮细胞的生长,加速其凋亡,而且可阻断EGF对气管上皮细胞生长的刺激作用,3种抑制剂的作用无明显差异.     

The structure and mode of action of different botulinum toxins

The seven serotypes (A–G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ecto‐acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca²⁺‐regulated exocytosis involving sensitive factor attachment protein‐25 (SNAP‐25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT‐A of nine amino acids from the C‐terminal of SNAP‐25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT‐A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP‐25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications.     

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.     

XGD-1对人外周血T淋巴细胞增殖和IL-2R表达的影响

目的 探讨XGD—l的免疫抑制作用及其作用机理。方法 不同浓度的XGD—l作用于植物血凝索(PHA)和刀豆索A(ConA)诱导的正常人外周血T淋巴细胞，共同培养48h和72h，用改良MTT法观察XGD—l对人T淋巴细胞增殖的影响，用流式细胞术检测XGD—l对T淋巴细胞表面IL—2R表达的影响；同时观察联合应用CsA和XGD—l对细胞增殖及IL—2R表达的影响。结果 XGD—l对PHA和ConA诱导的正常人外周血T淋巴细胞增殖有明显的抑制作用，其作用与药物浓度有关，在一定剂量范围内，抑制作用随XGD—l剂量的递增而加强；XGD—l对PHA和ConA激活的T淋巴细胞表面IL-2R的表达有显著抑制作用，阳性率从正常对照活化细胞的47．67％降为25．03％；联合应用CsA，上述抑制作用增强。结论 XGD-l具有免疫抑制作用，能降低IL-2R表达，可能是其免疫抑制作用的重要机理之一。     

Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms

Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never detected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic.     

Expression of the calcium receptor CaR in the parathyroid of secondary hyperparathyroidism patients

The effects of calcium on parathyroid hormone (PTH) has further discovered in recent years. It has been known that calcium ion concentration in the extracellular fluid is a major determinant of PTH secretion. The relationship between serum intact PTH (iPTH) and calcium ion levels is described by a sigmoidal curve. The calcium concentration that produces half-maximal change in PTH release (the midpoint between maximal and minimal     

Familial spontaneous pneumothorax in three generations and its HLA

We experienced a case of familial spontaneous pneumothorax in three generations. Six of 13 family members had episodes of spontaneous pneumothorax. It is well established that there are some diseases associated with human leukocyte antigen (HLA). We performed HLA phenotyping for HLA of A, B and C. In our study, we detected the HLA haplotype A2, B61 in three of 4 who had episodes of spontaneous pneumothorax. The HLA haplotype A2, B70 were also detected in three of 4 who had episodes. This suggests that familial spontaneous pneumothorax might have hereditary factors.     

表皮生长因子及其受体与流产关系的探讨

采用放射免疫竞争抑制饱和分析法，检测４７例难免流产患者，６５例人工流产及２０例健康非孕妇女血清表皮生长因子（ＥＧＦ）水平；同时采用免疫组织化学法检测流产者胚胎组织中表皮生长因子受体（ＥＧＦＲ）表达程度。结果：人工流产组血清ＥＧＦ水平高于自然流产及非孕妇女，而自然流产与非孕妇女差异无显著性；胚胎组织中ＥＧＦＲ阳性表达率人工流产组明显高于自然流产组。提示：ＥＧＦ通过与其受体结合对妊娠维持、胚胎及胎儿的     

Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.