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941.
Roman Paduch Martyna Kandefer‐Szerszeń Agnieszka Szuster‐Ciesielska Krzysztof Plewka 《Cell biology international》2010,34(2):213-223
Colon carcinoma invasiveness is a process involving cell–cell and cell–matrix alterations, local proteolysis of the ECM (extracellular matrix) or changes in cytokine and growth factor levels. In order to evaluate the role of TGF‐β1 (transforming growth factor‐β1) and small G protein RhoA in tumour progression, the influence of TGF‐β1 treatment or RhoA‐associated kinase inhibitor on the production of NO (nitric oxide) and MMP‐2 and MMP‐9 (metalloproteinases‐2 and ‐9) was analysed in three human colon adenocarcinoma cell lines (HT29, LS180, SW948) representing different stages of tumour development. All the tested cell lines produced low amounts of MMP‐2 and MMP‐9. rhTGF‐β1 and the synthetic Rho kinase inhibitor (Y‐27632) decreased MMP‐2 secretion by colon cancer cells, especially in the most advanced stage of colon cancer. rhTGF‐β1 decreased NO secretion by cells, while Y‐27632 had no effect on it. Immunoblotting with anti‐RhoA antibodies followed by densitometry revealed that RhoA levels were slightly increased after incubation of colon carcinoma cells (SW948) with rhTGF‐β1. rhTGF‐β1 induced α‐smooth muscle actin (α‐SMA) expression, especially in high Duke's grade of colon cancer, while Y‐27632 blocked it. Summing up, in colon carcinoma cells, TGF‐β1 and RhoA protein may regulate tumour invasiveness measured as MMP, NO and α‐SMA expression or assayed using motility data and may be a good target for cancer therapy. 相似文献
942.
Palczewska G Maeda T Imanishi Y Sun W Chen Y Williams DR Piston DW Maeda A Palczewski K 《Nature medicine》2010,16(12):1444-1449
Multiphoton excitation fluorescence microscopy (MPM) can image certain molecular processes in vivo. In the eye, fluorescent retinyl esters in subcellular structures called retinosomes mediate regeneration of the visual chromophore, 11-cis-retinal, by the visual cycle. But harmful fluorescent condensation products of retinoids also occur in the retina. We report that in wild-type mice, excitation with a wavelength of ~730 nm identified retinosomes in the retinal pigment epithelium, and excitation with a wavelength of ~910 nm revealed at least one additional retinal fluorophore. The latter fluorescence was absent in eyes of genetically modified mice lacking a functional visual cycle, but accentuated in eyes of older wild-type mice and mice with defective clearance of all-trans-retinal, an intermediate in the visual cycle. MPM, a noninvasive imaging modality that facilitates concurrent monitoring of retinosomes along with potentially harmful products in aging eyes, has the potential to detect early molecular changes due to age-related macular degeneration and other defects in retinoid metabolism. 相似文献
943.
From the mid-1960s onwards, it was believed that only two human coronavirus species infect humans: HCoV-229E and HCoV-OC43. Then, in 2003, a novel member of the coronavirus family was introduced into the human population: SARS-CoV, causing an aggressive lung disease. Fortunately, this virus was soon expelled from the human population, but it quickly became clear that the human coronavirus group contains more members then previously assumed, with HCoV-NL63 identified in 2004. Despite its recent discovery, ample results from HCoV-NL63 research have been described. We present an overview of the publications on this novel coronavirus. 相似文献
944.
LHRH analogs have become a promising modality in prostate cancer therapy as an alternative to surgical castration, and the use of these agents is generally considered to be safe. Since now, only few cases of an apoplexy of previously undiagnosed pituitary adenoma (usually gonadotropinoma) at the beginning of therapy have been described in the medical literature. We present a case of a 74 year old patient who was diagnosed of prostate cancer at the age of 68. There was no evidence of metastatic disease. Radical prostatectomy was performed and LHRH analog gosereline (Zoladex 3.6 mg s.c.) was administered. During the first day after gosereline injection the patient developed headaches that became more severe over the next 3 days. Then the patient experienced nausea and vomiting, double vision and eyelid ptosis. On the 5th day the patient temporarily lost consciousness and was admitted to hospital. Imaging (computerized tomography, magnetic resonance imaging) revealed the presence of a pituitary tumor and hemorrhage within the gland. There was no evidence of pituitary dysfunction in hormonal studies. Neurosurgical intervention was postponed for 5 days after admission. Pathological mass with signs of recent hemorrhage was removed via transsphenoidal route. The tumor had negative immunohistochemical GH, ACTH and PRL staining. Neurological impairment resolved within 9 months after the operation. As a result the patient required adrenal and thyroid replacement. During 6 years of follow-up there was no evidence of prostate cancer recurrence. 相似文献
945.
Zabłotna E Kret A Jaśkiewicz A Olma A Leplawy MT Rolka K 《Biochemical and biophysical research communications》2006,340(3):823-828
In many complexes formed by serine proteinases and their inhibitors, the hydroxyl group provided by water molecule or by the inhibitor Ser residue is located close to the inhibitor P1-P1' reactive site. In order to investigate the role of this group, we synthesized analogues of trypsin inhibitor SFTI-1 isolated from the seeds of sunflower modified in P1 by alpha-hydroxymethylserine (HmSer) and both enantiomers of alpha-hydroxymethylvaline (HmVal). All the synthesized analogues inhibited bovine beta-trypsin and human leukocyte elastase. SFTI-1 analogues with HmVal and HmSer appear to be potent inhibitors of bovine beta-trypsin, whereas [Val5]SFTI-1 is practically inactive. Also trypsin inhibitory activity of [Ser5]SFTI-1 is significantly lower. Since the electrostatic interaction between protonated epsilon-NH2 group of the inhibitor P1 position and beta-carboxylate of trypsin Asp189 is the main driving force for interaction of both molecules, the results obtained are very interesting. We believe that these SFTI-1 analogues belong to a novel class of serine proteinase inhibitors. 相似文献
946.
Assessment of sources of uncertainty in macrophyte surveys
and the consequences for river classification 总被引:2,自引:2,他引:0
Ryszard Staniszewski Krzysztof Szoszkiewicz Janina Zbierska Jacek Lesny Szymon Jusik Ralph T. Clarke 《Hydrobiologia》2006,566(1):235-246
The application of macrophytes in freshwater monitoring is still relatively limited and studies on their intercalibration
and sources of variation are required. Therefore, the aim of the study was to compare selected indices and metrics based on
macrophytes and to quantify their variability. During the STAR project, several aspects influencing uncertainty in estimation
of the ecological quality of river were assessed. Results showed that several metrics based on the indicative value of plant
species can be used in evaluation of the ecological status of rivers. Among estimated sources of variance in metric values
the inter-surveyor differences had the lowest effect and slightly stronger were the influences of temporal variation (years
and seasons) and shading. The impact of habitat modification was the most important factor. Analysis showed that some of macrophyte-based
metrics (notably MTR and IBMR) are of sufficient precision in terms of sampling uncertainty, that they could be useful for
estimating the ecological status of rivers in accordance with the aims of the Water Framework Directive. 相似文献
947.
The interactions between sensitivity and variability of macrophyte and diatom communities were evaluated as a research support
of methodologies required by the Water Framework Directive. Slope and shading were identified as additional typological parameters
improving links between unimpacted macrophyte communities and running water types. Two other studies demonstrated indication
value of macrophytes for assessment of nutrient enrichment and hydromorphological degradation. The special exercises were
realized within the STAR project to evaluate sources of variability/uncertainty in assessment methods based on macrophytes
and diatoms. Sampling period and shading of the site were found as major factors affecting variability in macrophyte assessment
results. Uncertainty of diatom assessment is predominantly associated with selection of site, substrate type and taxonomic
identification. Further extension of indication systems and definition of macrophyte/diatom-specific typology of running waters
are considered as the main aims of subsequent investigations. 相似文献
948.
Kołomecki K Maciaszczyk P Stepień H Cywiński J Cielecka J Stepień T Kuzdak K 《Endokrynologia Polska》2006,57(4):320-325
INTRODUCTION: Apoptosis (programmed cell death) is the best described mode of physiological cell death. During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is external protein signal originating from other cell--also named as "death signal". Another one is specific cell reaction for external stress factors. Blood concentration of proteins regulating both pathways of apoptosis may be useful in early diagnosis and staging of thyroid tumors. The aim of study was evaluation of p53 and sFasL blood concentration in patients with benign follicular adenoma and follicular thyroid cancer. MATERIALS AND METHODS: The study population was composed of 28 patients: 14 with thyroid carcinoma and 14 patients with follicular neoplasm (NF). All patients underwent surgical treatment. P53 and sFasL levels were evaluated before surgery and related to the histopathological diagnosis obtained post-surgery. RESULTS: The analysis revealed high sFasL blood concentration in patients with follicular thyroid cancer in comparison with the group with follicular adenoma. There was no statistically significant difference between levels of p53 in both groups. CONCLUSIONS: Evaluation of sFasL serum level concentration may be useful in preoperative diagnosis of follicular thyroid tumors. 相似文献
949.
Two membrane-bound isoforms of cytochrome b5 have been identified in mammals, one associated with the outer mitochondrial membrane (OM b5) and the other with the endoplasmic reticulum (microsomal, or Mc b5). The soluble heme binding domains of OM and Mc b5 have highly similar three-dimensional structures but differ significantly in physical properties, with OM b5 exhibiting higher stability due to stronger heme association. In this study, we present results of 8.5-ns length molecular dynamics simulations for rat Mc b5, bovine Mc b5, and rat OM b5, as well as for two rat OM b5 mutants that were anticipated to exhibit properties intermediate between those of rat OM b5 and the two Mc proteins: the A18S/I32L/L47R triple mutant (OM3M) and the A18S/I25L/I32L/L47R/L71S quintuple mutant (OM5M). Analysis of the structure, fluctuations, and interactions showed that the five b5 variants used in this study differed in organization of their molecular surfaces and heme binding cores in a way that could be used to explain certain experimentally observed physical differences. Overall, our simulations provided qualitative microscopic explanations of many of the differences in physical properties between OM and Mc b5 and two mutants in terms of localized changes in structure and flexibility. They also reveal that opening of a surface cleft between hydrophobic cores 1 and 2 in bovine Mc b5, observed in two previously reported simulations (E. M. Storch and V. Daggett, Biochemistry, 1995, Vol. 34, pp. 9682-9693; A. Altuve, Biochemistry, 2001, Vol. 40, pp. 9469-9483), probably resulted from removal of crystal contacts and likely does not occur on the nanosecond time scale. Finally, the MD simulations of OM5M b5 verify that stability and dynamic properties of cytochrome b5 are remarkably resistant to mutations that dramatically alter the stability and structure of the apoprotein. 相似文献
950.
Release of the soluble transferrin receptor is directly regulated by binding of its ligand ferritransferrin 总被引:1,自引:0,他引:1
Dassler K Zydek M Wandzik K Kaup M Fuchs H 《The Journal of biological chemistry》2006,281(6):3297-3304
The human transferrin receptor (TfR) is shed by an integral metalloprotease releasing a soluble form (sTfR) into serum. The sTfR reflects the iron demand of the body and is postulated as a regulator of iron homeostasis via binding to the hereditary hemochromatosis protein HFE. To study the role of transferrin in this process, we investigated TfR shedding in HL60 cells and TfR-deficient Chinese hamster ovary cells transfected with human TfR. Independent of TfR expression, sTfR release decreases with increasing ferritransferrin concentrations, whereas apo-transferrin exhibits no inhibitory effect. To investigate the underlying mechanism, we generated several TfR mutants with different binding affinities for transferrin. Shedding of TfR mutants in transfected cells correlates exactly with their binding affinity, implying that the effect of ferritransferrin on TfR shedding is mediated by a direct molecular interaction. Analysis of sTfR release from purified microsomal membranes revealed that the regulation is independent from intracellular trafficking or cellular signaling events. Our results clearly demonstrated that sTfR does not only reflect the iron demand of the cells but also the iron availability in the bloodstream, mirrored by iron saturation of transferrin, corroborating the important potential function of sTfR as a regulator of iron homeostasis. 相似文献