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111.
112.
Rehnberg J Zendehrokh N Dejmek A 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2007,29(4):217-220
OBJECTIVE: To determine the proliferation rates of mesothelial cells in metastatic and benign effusions. STUDY DESIGN: Immunohistochemistry was performed on formalin-fixed pellets from 16 malignant and 9 benign clinical effusions. Dual staining with antibodies against Ki-67 (MIB-1) and desmin was applied to all effusions to differentiate between benign mesothelial cells and malignant cells, and the proportions of desmin+/Ki-67+ and desmin+/Ki-67- cells were calculated. RESULTS: In 7 malignant effusions no proliferating mesothelial cells were found, whereas some rate of proliferation could always be demonstrated in mesothelial cells in the benign effusions. Further, the median proportions of proliferating cells, malignant 2% vs. benign 11%, differed significantly. CONCLUSIONS: To our knowledge this finding has not been previously described, and it may have implications for both cytologic diagnosis and the understanding of tumor biology and the interaction between tumor cells and mesothelial cells. 相似文献
113.
Rainer Voisard Tanja Krügers Barbara Reinhardt Bianca Vaida Regine Baur Tina Herter Anke Lüske Dorothea Weckermann Karl Weingärtner Wolfgang Rössler Vinzenz Hombach Thomas Mertens 《BMC microbiology》2007,7(1):1-6
Background
The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.Results
During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.Conclusion
The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed. 相似文献114.
Svea Dittmann Annika Schmid Susanna Richter Konrad Trülzsch Jürgen Heesemann Gottfried Wilharm 《BMC microbiology》2007,7(1):67
Background
Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica) share a virulence plasmid encoding a type three secretion system (T3SS). This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins), the specific Yop chaperones (Sycs), and the Ysc (Yop secretion) proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study. 相似文献115.
116.
Roldan M de Guia Adam J Rose Anke Sommerfeld Oksana Seibert Daniela Strzoda Annika Zota Yvonne Feuchter Anja Krones‐Herzig Tjeerd Sijmonsma Milen Kirilov Carsten Sticht Norbert Gretz Geesje Dallinga‐Thie Sven Diederichs Nora Klöting Matthias Blüher Mauricio Berriel Diaz Stephan Herzig 《The EMBO journal》2015,34(3):344-360
In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC therapy and certain components of the Metabolic Syndrome, including obesity and insulin resistance. Here, we identify the hepatic induction of the mammalian conserved microRNA (miR)‐379/410 genomic cluster as a key component of GC/GR‐driven metabolic dysfunction. Particularly, miR‐379 was up‐regulated in mouse models of hyperglucocorticoidemia and obesity as well as human liver in a GC/GR‐dependent manner. Hepatocyte‐specific silencing of miR‐379 substantially reduced circulating very‐low‐density lipoprotein (VLDL)‐associated triglyceride (TG) levels in healthy mice and normalized aberrant lipid profiles in metabolically challenged animals, mediated through miR‐379 effects on key receptors in hepatic TG re‐uptake. As hepatic miR‐379 levels were also correlated with GC and TG levels in human obese patients, the identification of a GC/GR‐controlled miRNA cluster not only defines a novel layer of hormone‐dependent metabolic control but also paves the way to alternative miRNA‐based therapeutic approaches in metabolic dysfunction. 相似文献
117.
Initial design and physical characterization of a polymeric device for osmosis‐driven delayed burst delivery of vaccines
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118.
David W. Frederick James G. Davis Antonio Dávila Jr. Beamon Agarwal Shaday Michan Michelle A. Puchowicz Eiko Nakamaru-Ogiso Joseph A. Baur 《The Journal of biological chemistry》2015,290(3):1546-1558
The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. 相似文献
119.
Annika S?derholm Xiaohu Guo Matilda S. Newton Gary B. Evans Joakim N?svall Wayne M. Patrick Maria Selmer 《The Journal of biological chemistry》2015,290(41):24657-24668
HisA is a (βα)8 barrel enzyme that catalyzes the Amadori rearrangement of N′-[(5′-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (ProFAR) to N′-((5′-phosphoribulosyl) formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide (PRFAR) in the histidine biosynthesis pathway, and it is a paradigm for the study of enzyme evolution. Still, its exact catalytic mechanism has remained unclear. Here, we present crystal structures of wild type Salmonella enterica HisA (SeHisA) in its apo-state and of mutants D7N and D7N/D176A in complex with two different conformations of the labile substrate ProFAR, which was structurally visualized for the first time. Site-directed mutagenesis and kinetics demonstrated that Asp-7 acts as the catalytic base, and Asp-176 acts as the catalytic acid. The SeHisA structures with ProFAR display two different states of the long loops on the catalytic face of the structure and demonstrate that initial binding of ProFAR to the active site is independent of loop interactions. When the long loops enclose the substrate, ProFAR adopts an extended conformation where its non-reacting half is in a product-like conformation. This change is associated with shifts in a hydrogen bond network including His-47, Asp-129, Thr-171, and Ser-202, all shown to be functionally important. The closed conformation structure is highly similar to the bifunctional HisA homologue PriA in complex with PRFAR, thus proving that structure and mechanism are conserved between HisA and PriA. This study clarifies the mechanistic cycle of HisA and provides a striking example of how an enzyme and its substrate can undergo coordinated conformational changes before catalysis. 相似文献
120.
Noelia Inés Burgardt Andreas Schmidt Annika Manns Alexandra Schutkowski Günther Jahreis Yi-Jan Lin Bianca Schulze Antonia Masch Christian Lücke Matthias Weiwad 《The Journal of biological chemistry》2015,290(27):16708-16722
Recently we have shown that the peptidyl-prolyl cis/trans isomerase parvulin 17 (Par17) interacts with tubulin in a GTP-dependent manner, thereby promoting the formation of microtubules. Microtubule assembly is regulated by Ca2+-loaded calmodulin (Ca2+/CaM) both in the intact cell and under in vitro conditions via direct interaction with microtubule-associated proteins. Here we provide the first evidence that Ca2+/CaM interacts also with Par17 in a physiologically relevant way, thus preventing Par17-promoted microtubule assembly. In contrast, parvulin 14 (Par14), which lacks only the first 25 N-terminal residues of the Par17 sequence, does not interact with Ca2+/CaM, indicating that this interaction is exclusive for Par17. Pulldown experiments and chemical shift perturbation analysis with 15N-labeled Par17 furthermore confirmed that calmodulin (CaM) interacts in a Ca2+-dependent manner with the Par17 N terminus. The reverse experiment with 15N-labeled Ca2+/CaM demonstrated that the N-terminal Par17 segment binds to both CaM lobes simultaneously, indicating that Ca2+/CaM undergoes a conformational change to form a binding channel between its two lobes, apparently similar to the structure of the CaM-smMLCK796–815 complex. In vitro tubulin polymerization assays furthermore showed that Ca2+/CaM completely suppresses Par17-promoted microtubule assembly. The results imply that Ca2+/CaM binding to the N-terminal segment of Par17 causes steric hindrance of the Par17 active site, thus interfering with the Par17/tubulin interaction. This Ca2+/CaM-mediated control of Par17-assisted microtubule assembly may provide a mechanism that couples Ca2+ signaling with microtubule function. 相似文献