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排序方式: 共有150条查询结果,搜索用时 31 毫秒
1.
David E. Kerr Peter D. Senter William V. Burnett David L. Hirschberg Ingegerd Hellström Karl Erik Hellström 《Cancer immunology, immunotherapy : CII》1990,31(4):202-206
Summary The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localizaton of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These were hydrolyzed by PVA to doxorubicin and melphalan respectively.In vitro studies with the L6-positive lung carcinoma cell line, H2981, and the 1F5-positive B-cell lymphoma line, Daudi, showed that DPO was 80-fold less toxic to H2981 cells and 20-fold less toxic to Daudi cells than doxorubicin, and its toxicity was substantially increased when the H2981 cells were pretreated with L6-PVA or the Daudi cells were pretreated with 1F5-PVA. The cytotoxic effect was antigen-specific, since only the binding mAb-enzyme conjugate increased the cytotoxicity of the prodrug. MelPO was more than 1000-fold less toxic than melphalan to H2981 cells and more than 100-fold less toxic than melphalan to Daudi cells. Pretreatment with the mAb-PVA conjugates did not enhance the toxicity of MelPO in either cell line, because PVA hydrolyzes the phenoxyacetamide bond of MelPO too slowly to generate a toxic level of melphalan. 相似文献
2.
PD Dr. G. F. Jirikowski J. F. Ramalho-Ortigao K. W. Kesse F. E. Bloom 《Histochemistry and cell biology》1990,94(2):187-190
Summary We recently described a nonradioactive method for in situ hybridization with 5-bromo-2-deoxyuridine (BrdU) labelled oligonucleotide
probes. An antibody to BrdU and immunocytochemistry were used in order to detect the hybridization signal. We have now applied
this method to semithin Epon sections, in order to hybridize consecutive sections through single cells with different probes
and to stain them with antibodies to neuropeptides. It could be shown that Epon embedding preserves mRNA well. In the present
study we used a BrdU labelled synthetic oligonucleotide probe complementary to a fragment of the vasopressin precursor and
an antibody to Arg-vasopressin. Vasopressin mRNA was demonstrable in a fraction of the vasopressin immunoreactive neurons
in the magnocellular nuclei. In addition some of the magnocellular neurons showed either hybridization or vasopressin immunostaining
only, perhaps indicating different stages of synthetic and secretory activity.
The method described seems to be a valuable tool for studying synthetic activity in peptidergic neurons on a single cell level.
The method might also have potential for in situ hybridization on the electronmicroscopical level. 相似文献
3.
Effects of trypsin on secretion stimulated by micromolar Ca2+ and phorbol ester in digitonin-permeabilized adrenal chromaffin cells 总被引:1,自引:0,他引:1
1. Catecholamine secretion from digitonin-treated chromaffin cells is stimulated directly by micromolar Ca2+ in the medium. The permeabilized cells are leaky to proteins. 2. In this study trypsin (30-50 micrograms/ml) added to cells after digitonin treatment completely inhibited subsequent Ca2+-dependent catecholamine secretion. The same concentrations of trypsin did not inhibit secretion from permeabilized cells if trypsin was present only prior to cell permeabilization. 3. The data indicate that trypsin entered digitonin-treated chromaffin cells which were capable of undergoing secretion and that an intracellular, trypsin-sensitive protein is involved in secretion. Chymotrypsin was less potent but had effects similar to those of trypsin. 4. The enhancement of Ca2+-dependent secretion from permeabilized chromaffin cells induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by trypsin added simultaneously with Ca2+ to permeabilized cells at concentrations (3-10 micrograms/ml) which had little or no effect on Ca2+-dependent secretion from cells untreated with TPA. Ca2+-dependent secretion in TPA-treated cells was reduced by trypsin only to the level that would have occurred in cells not treated with TPA. Trypsin reduced the large TPA-induced increment of membrane-bound protein kinase C. 相似文献
4.
Thomas P. Senter David H. Stimson Gerald Charles Richard J. Brand 《The Western journal of medicine》1983,139(5):657-662
In a masked, randomized, concurrently controlled clinical trial we compared the therapeutic response of two regimens in which the same topical corticoid was used to treat 52 men who had stable psoriasis. One regimen, called reduced dose, consisted of once-a-day application of a representative potent fluorinated topical steroid ointment, fluocinonide (Lidex), combined with three-times-a-day application of its vehicle. The other regimen, called traditional dose, consisted of four-times-a-day topical application of the same steroid. Patients were assigned to one of the two regimens and observed for six weeks. Confidence intervals for the difference in true mean response under these two regimens provide good evidence that for these patients the traditional dose was not clinically superior to the reduced dose. 相似文献
5.
6.
Summary The microproblematicumPycnoporidium ? eomesozoicum
Flügel, 1972, from Upper Triassic reefs of the Alpine-Mediterranean region, Turkey Oman and Iran (originally interpreted as possible
alga) represents the type species of a new strophomenid brachiopod genus (Gosaukammerella n.g.). The genus is characterized by a very small, millimeter-sized plano-convex shell, whose ventral valve is attached to
the substratum (mainly sponges) by symmetrically arranged outgrowths developing from a pseudopunctate, lamellose foliated
shell wall and composed of densely spaced subparallel ‘tubes’ comparable with productide spines secreted by papillose extensions
of the mantle.Gosaukammerella seems to be the only reliable candidate for the existence of post-Paleozoic strophomenid (productid ?) brachiopods.
Gosaukammerella eomesozoica is restricted to possibly cryptic, shaded reef environments inhabited predominantly by sponges serving as substrates for
micromorphic brachiopods. 相似文献
7.
Summary Intercellular junctions in the uterine epithelium of the ovoviviparous urodele Salamandra salamandra were studied in pregnant and non-pregnant females by freeze-fracture technique. Junctional complexes consist of zonulae occludentes (tight junctions) and numerous maculae adhaerentes (desmosomes); z. adhaerentes and nexuses (gap junctions) could not be identified. Tight junctions are of the flexible type exhibiting loosely interconnected fibrils. The fibrillary network appears stretched more often in pregnant females possibly due to the mechanical stress of pregnancy. The structure and occurrence of the junctions identified, especially that of the tight junctions, is discussed with regard to the functions of the uterus during pregnancy.Zusammenfassung Mit Hilfe der Gefrierbruchtechnik wurden im Uterus-epithel trächtiger und nichtträchtiger Feuersalamanderweibchen (Salamandra salamandra) Zonulae occludentes und Maculae adhaerentes, jedoch keine Z. adhaerentes sowie Nexus identifiziert. Die Z. occludentes sind flexibel. Ihr fibrilläres Netzwerk ist bei trächtigen Weibchen öfter gestreckt; das ist möglicherweise auf die stärkere Ausdehnung des Uterusgewebes während der Trächtigkeit zurückzuführen. Das Vorkommen der verschiedenen Kontakt-strukturen, namentlich das der Z. occludentes, wird im Hinblick auf die Funktionen des Uterus während der Trächtigkeit diskutiert.We are indebted to Mrs. K. Ott for excellent technical assistance and to Miss Dr. U. Beigel for linguistic help 相似文献
8.
9.
Monoclonal antibody-beta-lactamase conjugates for the activation of a cephalosporin mustard prodrug.
H P Svensson J F Kadow V M Vrudhula P M Wallace P D Senter 《Bioconjugate chemistry》1992,3(2):176-181
Cephalosporin mustard (CM) was designed as an anticancer prodrug that could be activated in a site-specific manner by monoclonal antibody-beta-lactamase conjugates targeted to antigens present on tumor cell surfaces. Purified beta-lactamases from Bacillus cereus (BC beta L) and Escherichia coli (EC beta L) catalyzed the release of phenylenediamine mustard (PDM) from CM through a fragmentation reaction which occurs after the beta-lactam ring of CM is hydrolyzed. The Km and Vmax values were 5.7 microM and 201 mumol/min per mg for BC beta L and 43 microM and 29 mumol/min per mg for EC beta L, respectively. Conjugates of BC beta L were prepared by combining the F(ab')2 fragments of the maleimide-substituted monoclonal antibodies L6 and 1F5 with thiolated BC beta L. The conjugates showed little loss in enzymatic activity and bound nearly as well as the unmodified F(ab')2 monoclonal antibodies to antigens expressed on the H2981 human lung adenocarcinoma cell line (L6 positive, 1F5 negative). PDM was approximately 50-fold more cytotoxic than CM to H2981 cells. Treatment of the cells with L6-BC beta L followed by CM resulted in a level of cytotoxic activity that was comparable to that of PDM. This was most likely due to activation of CM by conjugate that bound to cell-surface antigens, since pretreatment of H2981 cells with BC beta L or 1F5-BC beta L enhanced the activity of CM to a lesser extent. Thus, we have shown that CM is a prodrug, and that it can be activated with immunological specificity by a monoclonal antibody-beta-lactamase conjugate. 相似文献
10.
In vitro and in vivo activities of monoclonal antibody-alkaline phosphatase conjugates in combination with phenol mustard phosphate. 总被引:2,自引:0,他引:2
The prodrug p-[N,N-bis(2-chloroethyl)amino]phenyl phosphate (phenol mustard phosphate, POMP) was prepared from p-[N,N-bis(2-chloroethyl)amino]phenol (phenol mustard, POM) by phosphorylation with phosphoryl chloride, followed by aqueous hydrolysis. It was found that POMP was much less cytotoxic than POM when tested against H2981 human lung and H3396 human breast carcinoma cells in vitro. Pretreatment of the H2981 cells with L6-alkaline phosphatase (L6-AP), a monoclonal antibody conjugate that could bind to cell surface antigens, greatly enhanced the cytotoxic effects of POMP in an immunologically specific manner. Owing to its reduced toxicity in nude mice, larger amounts of POMP compared to POM could be administered. Neither agent exhibited significant in vivo antitumor activity when tested against subcutaneous H2981 tumors in nude mice. However, antitumor activity was observed in animals receiving L6-AP 48 h prior to POMP administration. This level of activity was greater than with the drugs alone, or a combination of 1F5-AP (nonbinding control) with POMP. 相似文献