Effects of monoclonal antibodies on the function of acetylcholine receptors purified from Torpedo californica and reconstituted into vesicles

We tested the effects of 62 monoclonal antibodies (mAbs) to acetylcholine receptors from Torpedo californica on the function of receptor reconstituted into lipid vesicles. Two of these mAbs, mAbs 148 and 168, inhibited carbamylcholine-induced 22Na+ uptake into vesicles. The rate of 125I-labeled alpha-bungarotoxin (125I-alpha BGT) binding to the reconstituted liposomes was also reduced, although 125I-alpha BGT binding at equilibrium was not affected. Agonist-induced desensitization of the receptor was also affected by these mAbs. mAb 148 binds to the beta subunit of receptor, and mAb 168 binds to the gamma subunit. Both mAbs bind to the cytoplasmic surface of the receptor; correspondingly, both block function when added before reconstitution, and both were found to have no effect on function when added to preformed vesicles. Their effects were not due to interference with the reconstitution process. Both mAbs were capable of cross-linking receptors. In contrast to the bivalent mAbs, monovalent Fab fragments of these two mAbs had little effect on receptor function, which suggests that the effects of the bivalent mAbs resulted primarily from cross-linking receptors.     

抗胃癌细胞系单克隆抗体PD4的初步研究

以胃癌细胞系MGC803免疫Balb/c小鼠,取其脾细胞与小鼠骨髓瘤细胞NS-1融合。经选择培养、筛选及克隆化,获得恒定地分泌抗胃癌细胞系单克隆抗体(MoAb)的杂交瘤细胞系PD4。MoAb PD4与3/4胃癌细胞系有强结合反应,与4/4肺癌细胞系有弱结合反应,但与淋巴细胞、ABO红细胞、骨髓细胞、二倍体成纤维细胞及经检测的其他肿瘤细胞均无反应。PD4抗原主要表达于靶细胞的膜上,不耐热,为分子量40kD的蛋白性抗原。该抗原与HLA抗原系统,血型抗原系统无关,亦不同于其他作者所报告的其他胃癌相关抗原。     

Epithelial cytoskeletal framework and nuclear matrix-intermediate filament scaffold: three-dimensional organization and protein composition

Madin-Darby canine kidney (MDCK) cells grow as differentiated, epithelial colonies that display tissue-like organization. We examined the structural elements underlying the colony morphology in situ using three consecutive extractions that produce well-defined fractions for both microscopy and biochemical analysis. First, soluble proteins and phospholipid were removed with Triton X-100 in a physiological buffer. The resulting skeletal framework retained nuclei, dense cytoplasmic filament networks, intercellular junctional complexes, and apical microvillar structures. Scanning electron microscopy showed that the apical cell morphology is largely unaltered by detergent extraction. Residual desmosomes, as can be seen in thin sections, were also well- preserved. The skeletal framework was visualized in three dimensions as an unembedded whole mount that revealed the filament networks that were masked in Epon-embedded thin sections of the same preparation. The topography of cytoskeletal filaments was relatively constant throughout the epithelial sheet, particularly across intercellular borders. This ordering of epithelial skeletal filaments across contiguous cell boundaries was in sharp contrast to the more independent organization of networks in autonomous cells such as fibroblasts. Further extraction removed the proteins of the salt-labile cytoskeleton and the chromatin as separate fractions, and left the nuclear matrix-intermediate filament (NM-IF) scaffold. The NM-IF contained only 5% of total cellular protein, but whole mount transmission electron microscopy and immunofluorescence showed that this scaffold was organized as in the intact epithelium. Immunoblots demonstrate that vimentin, cytokeratins, desmosomal proteins, and a 52,000-mol-wt nuclear matrix protein were found almost exclusively in the NM-IF scaffold. Vimentin was largely perinuclear while the cytokeratins were localized at the cell borders. The 52,000-mol-wt nuclear matrix protein was confined to the chromatin- depleted matrix and the desmosomal proteins were observed in punctate polygonal arrays at intercellular junctions. The filaments of the NM-IF were seen to be interconnected, via the desmosomes, over the entire epithelial colony. The differentiated epithelial morphology was reflected in both the cytoskeletal framework and the NM-IF scaffold.     

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.     

Long-acting contraceptive agents: Norethisterone esters of arylcarboxylic acids

The synthesis of esters of norethisterone (17α-ethynyl-17β-hydroxy-estr-4-en-3-one) with acids containing a benzene ring is described, two methods of esterification being compared in terms of yield and convenience. The activities of these esters as long-acting contraceptive agents have been evaluated.     

Aliesterase activity and reproduction in Musca domestica: Effects of DDT and metepa

The chemosterilant metepa, administered orally and topically to adult M. domestica, was found to reduce aliesterase activity, to reduce the hatch of eggs, and when administered orally it also prolonged the pre-ovipositional period. Orally administered DDT had little effect on aliesterase but did reduce egg viability. Selection of a strain of M. domestica with diazinon, in an attempt to increase its resistance to diazinon, had the unexpected result of the flies becoming more susceptible but concomitantly their level of aliesterase was significantly increased. The aliesterase level of the immature stages of M. domestica is reported.

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Zusammenfassung Es wurde festgestellt, daß das Chemosterilisans Metepa bei oraler oder topischer Applikation bei erwachsenen Stubenfliegen die Aliesterase-Aktivität herabsetzt, die Schlüpfrate der Eier vermindert und bei oraler Anwendung auch die Präovipositionszeit verlängert. Oral verabreichtes DDT hat wenig Einfluß auf die Aliesterase, setzt aber die Lebensfähigkeit der Eier herab. Die Selektion einer Linie von Musca domestica durch Diazinon mit dem Ziel, ihre Resistenz gegen Diazinon zu erhöhen, hatte das unerwartete Ergebnis, daß die Fliegen empfindlicher wurden, zugleich aber ihr Aliesterase-Spiegel signifikant anstieg. Der Aliesterase-Spiegel der nicht erwachsenen Stubenfliegen-Stadien wird angegeben.

     

抗菌免疫核糖核酸组份的分离及其活性测定

<正> 抗菌免疫核糖核酸(iRNA)已用于条件致病菌感染的临床治疗,并对其免疫活性做了全面的研究。现已证实iRNA能够诱导特异性抗体的产生和传递特异性的细胞免疫,并能诱生干扰素和白细胞间素Ⅰ、Ⅱ等淋巴因子和单核因子。但制备的iRNA是含有多种RNA种类的混合物,为明确各组份的免疫学功能,我们对iRNA进行了分离,并测定不同组份的免疫活性。