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161.
Paschke R Kalbitz J Paetz C Luckner M Mueller T Schmoll HJ Mueller H Sorkau E Sinn E 《Journal of inorganic biochemistry》2003,94(4):335-342
This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue. 相似文献
162.
163.
Lamprecht P Erdmann A Mueller A Csernok E Reinhold-Keller E Holl-Ulrich K Feller AC Bruehl H Gross WL 《Arthritis research & therapy》2003,5(1):R25-R31
Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (positive for the long human isoform of CD45) phenotype. We analyzed patients with biopsy-proven localized Wegener's granulomatosis (WG) (n = 5), generalized WG (n = 16) and age- and sex-matched healthy controls (n = 13) to further characterize memory T cells in WG. The cell-surface expression of CD45RO, CD45RA, CD62L, CCR3, CCR5 and CXCR3 was determined on blood-derived T cells by four-color flow cytometric analysis. The fractions of CCR5+ and CCR3+ cells within the CD4+CD45RO+ and CD8+CD45RO+ memory T cell populations were significantly expanded in localized and generalized WG. The mean percentage of Th1-type CCR5 expression was higher in localized WG. Upregulated CCR5 and CCR3 expression could also be detected on a fraction of CD45RA+ T cells. CD62L expression was seen on approximately half of the memory T cell populations expressing chemokine receptors. This study demonstrates for the first time that expression of the inducible inflammatory chemokine receptors CCR5 and CCR3 on CD45RO+ memory T cells, as well as on CD45RA+ T cells ('revertants'), contributes to phenotypic heterogeneity in an autoimmune disease, namely WG. Upregulated CCR5 and CCR3 expression suggests that the cells belong to the effector memory T cell population. CCR5 and CCR3 expression on CD4+ and CD8+ memory T cells indicates a potential to respond to chemotactic gradients and might be important in T cell migration contributing to granuloma formation and vasculitis in WG. 相似文献
164.
Development of a technology for automation and miniaturization of protein crystallization 总被引:3,自引:0,他引:3
Mueller U Nyarsik L Horn M Rauth H Przewieslik T Saenger W Lehrach H Eickhoff H 《Journal of biotechnology》2001,85(1):7-14
The usage of standard 96 well microplates for the screening of crystallization conditions of recombinant proteins offers several advantages when compared to commonly used crystallization plate formats. The adoption of robotic technology for plate and glass slide preparation within a "hanging drop" vapour diffusion crystallization experiment enables to work with an increased throughput at reduced costs. In addition to commercial pipetting devices with a 96-channel aspirator/dispenser, solenoid ink-jet technology was applied to form 250 nl droplets with a diameter of approximately 1 mm. This allows miniaturization of crystallization screening set-ups with an estimated ten-fold cost reduction when compared to commonly used 24 well plates. 相似文献
165.
Mueller A Raptis J Rice PJ Kalbfleisch JH Stout RD Ensley HE Browder W Williams DL 《Glycobiology》2000,10(4):339-346
Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction. 相似文献
166.
Kress W Collmann H Büsse M Halliger-Keller B Mueller CR 《Cytogenetics and cell genetics》2000,91(1-4):134-137
A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 25 Crouzon and 5 Pfeiffer syndrome patients, whereas no sequence alterations were found in the remaining patients, even after screening of the relevant parts of FGFR1, FGFR3, and TWIST. Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%). These two mutational hot spots, therefore, are prime targets for an efficient mutation-screening strategy. The spectrum of mutations overlapped the two syndromes and thus reflected the phenotypic similarities observed in both patient groups. In 21 families, the origin of the mutation could be traced by analyzing parents and relatives. Eleven mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably within the pedigree, but both syndromes "bred true," i.e., a Pfeiffer syndrome phenotype was never observed in a Crouzon syndrome family and vice versa. 相似文献
167.
Mueller HT Borg JP Margolis B Turner RS 《The Journal of biological chemistry》2000,275(50):39302-39306
Modulation of amyloid precursor protein (APP) metabolism plays a pivotal role in the pathogenesis of Alzheimer's disease. The phosphotyrosine-binding/protein interaction (PTB/PI) domain of X11alpha, a neuronal cytosolic adaptor protein, binds to the YENPTY sequence in the cytoplasmic carboxyl terminus of APP. This interaction prolongs the half-life of APP and inhibits Abeta40 and Abeta42 secretion. X11alpha/Mint-1 has multiple protein-protein interaction domains, a Munc-18 interaction domain (MID), a Cask/Lin-2 interaction domain (CID), a PTB/PI domain, and two PDZ domains. These X11alpha protein interaction domains may modulate its effect on APP processing. To test this hypothesis, we performed a deletion analysis of X11alpha effects on metabolism of APP(695) Swedish (K595N/M596L) (APP(sw)) by transient cotransfection of HEK 293 cells with: 1) X11alpha (X11alpha-wt, N-MID-CID-PTB-PDZ-PDZ-C), 2) amino-terminal deletion (X11alpha-DeltaN, PTB-PDZ-PDZ), 3) carboxyl-terminal deletion (X11alpha-DeltaPDZ, MID-CID-PTB), or 4) deletion of both termini (PTB domain only, PTB). The carboxyl terminus of X11alpha was required for stabilization of APP(sw) in cells. In contrast, the amino terminus of X11alpha was required to stimulate APPs secretion. X11alpha, X11alpha-DeltaN, and X11alpha-PTB, but not X11alpha-DeltaPDZ, were effective inhibitors of Abeta40 and Abeta42 secretion. These results suggest that additional protein interaction domains of X11alpha modulate various aspects of APP metabolism. 相似文献
168.
169.
Thermophilic organisms produce proteins of exceptional stability. To understand protein thermostability at the molecular level we studied a pair of cold shock proteins, one of mesophilic and one of thermophilic origin, by systematic mutagenesis. Although the two proteins differ in sequence at 12 positions, two surface-exposed residues are responsible for the increase in stability of the thermophilic protein (by 15.8 kJ mol-1 at 70 degrees C). 11.5 kJ mol-1 originate from a predominantly electrostatic contribution of Arg 3 and 5.2 kJ mol-1 from hydrophobic interactions of Leu 66 at the carboxy terminus. The mesophilic protein could be converted to a highly thermostable form by changing the Glu residues at positions 3 and 66 to Arg and Leu, respectively. The variation of surface residues may thus provide a simple and powerful approach for increasing the thermostability of a protein. 相似文献
170.