Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability

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Cytotoxic effector cells against HLA antigens in strong linkage disequilibrium: identification of a strong,new, CML determinant

Three sets of cytotoxic effector cells were generated against the A1, B8, DR3 haplotype using haptoidentical individuals in three different families. The three sets of effector cells generated against this haplotype showed excellent reproducibility testing, strong cytotoxicity against their specific targets, low autologous kill, and segregation with the sensitizing haplotype within the family. When tested against a panel of cells bearing all combinations the A1, B8. DR3 antigens, a hierarchy of contribution of the individual HLA antigens as CML target determinants was seen. A new strong target cell determinant was identified by cytotoxicity with one of the effector cells not explicable in terms of the A1, B8, DR3 antigens or known HLA cross-reactivity. A family study demonstrated that this determinant clearly segregates with HLA. The success of this approach in defining new CML determinants may result from the generation of effector cells across a single haplotype in strong linkage disequilibrium or from the presentation of CML determinants in the context of self.     

Estrogenic activity of estradiol and its metabolites in the ER-CALUX assay with human T47D breast cells

A number of metabolites of 17beta-estradiol were tested for their estrogenic activity using the ER-CA-LUX assay based on the increased expression of luciferase in exposed T47D breast cancer cells. E2beta and estrone showed similar potencies in the test, whereas E2alpha was 100 times less active. Incubation of cells with estrone (0.35 microM) resulted in the formation of E2beta, whereas the reverse reaction was observed for E2beta. The resulting equilibrium may explain the similar estrogenic potency of estrone in the test. The synthetic 17-hydroxy benzoate ester of E2beta was 3 times less active than the parent compound. The 17-hydroxy palmitate and oleate esters of E2beta, were respectively 25 and 200 times less active than the parent compound. The 2-hydroxy metabolites of E2beta and estrone showed a 5,000 to 10,000 fold lower activity. The 4-hydroxy metabolites were more potent than the 2-hydroxy metabolites, showing only a 20-200 times lower activity. The 2- and 4-methoxyesters of estrone were 700 times less active. It is concluded that the estrogenic potency of metabolites formed in cattle after treatment with E2beta, like estrone, E2alpha and especially the esters of E2beta, may be significant with respect to the potential risk of the use of estradiol for growth promotion in domestic animals in certain countries.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice

Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.     

氨氯地平与非洛地平缓释剂治疗原发性轻、中度高血压的随机、双盲平行对照研究

目的:对比氨氯地平与非洛地平缓释剂治疗轻中度原发性高血压的疗效和安全性;每日1次服药对24小时动态血压的影响;并对比药物漏服对血压控制的影响。方法:76例轻、中度高血压患者被随机、双盲分成两组,分别每日口服1次氨氯地平5～10mg(Ⅰ组)或非洛地平缓释剂5～10mg(Ⅱ组),治疗12周,并用24小时动态血压监测评价用药前后24小时血压变化情况及漏服48小时的血压变化。结果:氨氯地平治疗组舒张压降低15.1mmHg(治疗末为84.8mmHg),非洛地平缓释剂治疗组舒张压降低15.3mmHg(治疗末为85.0mmHg)。总有效率Ⅰ组病人为83.8％,Ⅱ组为87.9％(P=NS)。在药物的初始剂量下即能达到有效血压控制的病人数Ⅰ组为76％,Ⅱ组为52％(P<0.01)。药物漏服24和48h后,Ⅰ组临床血压仍低于140/90mmHg,24小时动态血压与漏服前相比无显著性差异,而Ⅱ组的临床血压高于140/90mmHg,临床血压和24小时动态血压与漏服前相比具有显著性差异。两治疗组的副作用发生率均较低。结论:氨氯地平与非洛地平缓释剂均能有效降低轻、中度高血压病人的血压,安全、疗效可靠,病人耐受性好,但漏服试验表明漏服24与48h氨氯地平仍能较好的控制血压。Ⅰ组的血压波动明显低于Ⅱ组。     

胃癌及癌前病变组织中雌激素受体和P21ras的表达及意义

目的 探讨雌激素受体（ＥＲ）和ｒａｓ原癌基因蛋白－Ｐ２ｒａｓ的表达在胃癌发生、发展中的作用及与胃癌生物学行为的关系。方法 采用免疫组化ＳＰ法。结果 ＥＲ在慢性浅表性胃炎（２０例）、异型增生（２１例）中均为阴性,胃癌（４０例）的表达阳性率为４０％,三组比较有显著性差异（Ｉ〈０．０５）。Ｐ２１＾ｒａｓ在慢性浅表性胃炎、异型增生、胃癌的表达阳性率分别为１０％、２３．８％、４７．５％,三组比较差异有显著性     

GnRHa对子宫肌瘤雌孕激素和表皮生长因子受体的影响

目的　探讨促性腺激素释放激素激动剂(GnRHa)对子宫肌瘤内雌、孕激素受体(ER、PR)、表皮生长因子受体(EGF-R)的影响。方法　测定13例子宫肌瘤患者经GnRHa治疗3月后肌瘤内雌、孕激素受体和EGF-R水平,并以28例未用药肌瘤作对照。结果　 GnRHa治疗组肌瘤内ER、PR、EGF-R水平明显低于对照组。结论　GnRHa除减少肌瘤内ER、PR外,使肌瘤内EGF-R的水平下降可能是GnRHa治疗子宫肌瘤的一个重要机制。