Reciprocal regulation of platelet responses to P2Y and thromboxane receptor activation

Summary.  Background:  Thromboxane A₂ and ADP are two major platelet agonists that stimulate two sets of G protein-coupled receptors to activate platelets. Although aggregation responses to ADP and thromboxane desensitize, there are no reports currently addressing whether activation by one agonist may heterologously desensitize responses to the other. Objectives:  To demonstrate whether responses to ADP or U46619 may be modulated by prior treatment of platelets with the alternate agonist, revealing a level of cross-desensitization between receptor systems. Results:  Here we show that pretreatment of platelets with either agonist substantially desensitizes aggregation responses to the other agonist. Calcium responses to thromboxane receptor activation are desensitized by preactivation of P2Y₁ but not P2Y₁₂ receptors. This heterologous desensitization is mediated by a protein kinase C (PKC)-independent mechanism. Reciprocally, calcium responses to ADP are desensitized by pretreatment of platelets with the thromboxane analogue, U46619, and P2Y₁₂-mediated inhibition of adenylate cyclase is also desensitized by pretreatment with U46619. In this direction, desensitization is comprised of two components, a true heterologous component that is PKC-independent, and a homologous component that is mediated through stimulated release of dense granule ADP. Conclusions:  This study reveals cross-desensitization between ADP and thromboxane receptor signaling in human platelets. Cross-desensitization is mediated by protein kinases, involving PKC-dependent and independent pathways, and indicates that alterations in the activation state of one receptor may have effects upon the sensitivity of the other receptor system.     

海洋放线菌—药物开发的新兴资源

近些年,海洋放线菌成为新药研发的重要来源,引起人们的关注,本文综述了海洋放线菌在分离方面取得的成绩,并介绍了通过传统筛选方法分离得到的生物活性代谢物,以及在与新化合物相关的基因挖掘和生物合成基因簇的异源表达方面取得的进展。     

Heterologous structure of coating antigen on sensitivity of ELISA for sulfamethazine: evidence from molecular similarity analysis

Six structurally similar sulfonamide haptens have been linked to ovalbumin by diazo-method used as coating antigen. An enzyme-linked immunosorbent assay (ELISA) was developed to investigate heterologous structure of coating haptens on sensitivity of ELISA for sulfamethazine. The sensitivities of ELISA, expressed as IC₅₀ values, ranged from 94 to 877 ng mL^{? 1} when six coating antigens were employed. The results suggested that the structural heterology of coating hapten had significant effect on ELISA sensitivity. In order to evaluate the relationship between the degree of hapten heterology and ELISA sensitivity, we used molecular similarity methods to qualitatively represent the degree of coating hapten heterology. The Molecular Access System (MACCS) structural keys and the Tanimoto similarity coefficient were used to calculate and compare the degree of coating hapten's similarity, and the authors found that the sensitivity of ELISA was not in direct proportion with degree of coating hapten heterology in the case of study.     

Pregnancy-associated glycoprotein (PAG) family localized in chorionic cells within the epitheliochorial/diffuse placenta of the alpaca (Lama pacos)

Pregnancy-associated glycoproteins (PAGs) are abundant embryo-originated products expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium of some ungulate species. This paper describes the cellular immunolocalization of the chorionic PAG family in the epitheliochorial placenta type of the alpaca (Lama pacos—Lp), in which the PAGs were named ‘LpPAGs’. Placental Lp sections (5 μm) of different females near mid-pregnancy (150 days post coitum; dpc), advanced pregnancy (244-263 dpc) and late pregnancy (347 dpc) were used for cross-species (heterologous—ht) double fluorescent immunohistochemistry (htdF-IHC). The htdF-IHC was performed with primary rabbit polyvalent anti-porcine PAG polyclonals. The LpPAG immuno-complexes were visualized with secondary goat anti-rabbit immunoglobulins-conjugated with Alexa 488 fluorophore (green), among all nuclei of placental cells stained with propidium iodide (red). This is the first study reporting the immunolocalization of the LpPAG family identified by htdF-IHC at the feto/maternal interface during different pregnancy stages of the alpaca. The most dominant and strongest immune-positive LpPAG signals were found in the well-developed chorionic cell layer. Our htdF-IHC indicated relatively high epitope resemblance to that of the PAGs in camelids and pigs. These data increase our general knowledge of chorionic PAG localization during pregnancy-stage dependent development of the epitheliochorial diffuse placenta type in the alpaca.     

SURAMIN ACTIVIY IN HUMAN HEAD AND NECK SQUAMOUS CELL CARCINOMA——Ⅱ.EFFECT OF SURAMIN ON HUMAN HEAD AND NECK CARCINOMA XENOGRAFTS AND RELATED TOXICITY AND PHARMACOKINETIC STUDIES IN NUDE MICE

In part Ⅰ of the study,we have demonstrated that suraminhas a marked antiproliferative effect on human head and neck squamous cellcarcinoma cell lines,In the present study,both toxicity and pharmacokineticstudies in nude mice were done.The treatment of nude mice bearing head andneck cancers with suramin showed that suramin had a minimal antitumor effect.The possible mechanism of suramin lacking antitumor effect is discussed.     

珊瑚人工骨复合游离骨膜瓣的肌内植入试验

珊瑚人工骨复合游离骨膜植入兔腓肠肌内，所有试样均有新生骨骼和血管组织生成，３周时新骨量占试样的１３．３±７．０，６周时为２２．３±７．０％，新骨于植入５天后开始发生，并持续６周以上。而单纯人工骨或骨膜肌内植入均无新骨产生。全部植入物未发现炎症和排斥反应。     

微囊化人嗜铬细胞对大鼠异种移植的免疫隔离作用

目的探讨微囊化人嗜铬细胞(ME-HCC)移植于大鼠眼前房或足胝部的免疫隔离作用。方法雌性SD大鼠48只,3月龄,体重180-250g。随机分为3组,HCC组、空微囊组、ME-HCC组,每组16只。HCC组、空微囊组、ME-HCC组分别将HCC、空微囊、ME-HCC移植于大鼠的眼前房(n=8)或足胝部(n=8)。移植术后7d大鼠断尾取血,测定白细胞介素-2(IL-2)、IgG和IgM浓度。移植术后28d 处死大鼠,光镜下观察右侧眼球或左侧足组织形态学变化。结果与HCC组比较,空微囊组和ME- HCC组大鼠血清IL-2、IgG、IgM浓度均降低(P<0.01);ME-HCC、空微囊组血清IL-2、IgG、IgM浓度比较差异无统计学意义(P>0.05)。HCC组大鼠眼前房和足胝部可见大量淋巴细胞和中性粒细胞浸润。空微囊组、ME-HCC组大鼠眼前房和足胝部仅见少量淋巴细胞和中性粒细胞。结论微囊化人HCC 对大鼠异种移植的免疫排斥具有隔离作用。