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61.
Budzisz E Brzezinska E Krajewska U Rozalski M 《European journal of medicinal chemistry》2003,38(6):597-603
The cytotoxic effects and alkylating activity of a series of 3-[1-(alkylamino)-ethylidene]-chroman-2,4-dione (4a-4c), 2-methoxy-3-[1-(alkylamino)-ethylidene]-2,3-dihydro-2,4-dioxo-2lambda(5)-benzo[e][1,2] oxaphosphinane (5a-5c) and [2-oxo-4-phenyl(alkyl)-2H-chromen-3-yl]-phosphonic acids dimethyl ester (6a-6c) on the two leukemia cell lines HL-60 and NALM-6 have been determined. The test compounds are much more toxic to NALM-6 cells than to HL-60 cells. IC(50) data are up to nine times lower for the NALM-6 than for the HL-60 cell lines. As determined in an in vitro Preussmann test phosphonic derivatives 6a-6c possess very high (+++) alkylating activity, phosphoric derivatives 5a-5c are less active (++) while the derivatives 4a-4c can be included in the group of low activity (+) alkylating agents. Using regression analysis QSAR we found a relationship between biological activity and the physicochemical properties of the test compounds. Their cytotoxic effect increases with an increase of the hydrophobic parameters in the region of the substituents at the 2-, 3- and 4-positions of the benzopyrone skeleton of 4-6. 相似文献
62.
(1) We examined whether beta3- and/or atypical beta-adrenoceptors relax the rat isolated mesenteric artery. (2) Mesenteric arteries precontracted with phenylephrine were relaxed by beta-agonists with the following potencies (pD2): nonselective agonist isoprenaline (6.00)>nonconventional partial agonist cyanopindolol (5.45)>beta2-agonist fenoterol (4.98)>nonconventional partial agonist CGP 12177 (4.19)>beta3-agonist ZD 2079 (3.72). The beta3-agonist CL 316243 1 mm relaxed the vessel only marginally. (3) The concentration-response curves (CRCs) for cyanopindolol, CGP 12177 and ZD 2079 were not affected by the nonselective beta-antagonist propranolol 0.3 microm, the beta2-antagonist ICI 118551 1 microm and by CL 316243 60 microm, but shifted to the right by bupranolol (pA2 5.3-5.7), CGP 20712 (5.4) and SR 59230A (6.5-6.7) (the latter three drugs block atypical and/or beta3-adrenoceptors at high concentrations). (4) The CRC for isoprenaline was shifted to the right by propranolol (pA2 7.0) but, in the presence of propranolol 0.3 microm, not affected by SR 59230A 1 microm. The CRC for fenoterol was shifted to the right by propranolol (pA2 6.9) and ICI 118551 (6.8). (5) Removal of endothelium diminished the vasorelaxant effects of cyanopindolol, CGP 12177 and ZD 2079. (6) Fenoterol and cyanopindolol also relaxed (endothelium-intact) mesenteric arteries precontracted with serotonin. The relaxant effect of cyanopindolol was antagonized by bupranolol to about the same degree as in phenylephrine-contracted vessels. (7) In conclusion, beta2- and atypical beta-adrenoceptors (but not beta3-adrenoceptors) relax the rat mesenteric artery. The atypical beta-adrenoceptor, which is partially located endothelially, may differ from the low-affinity state of the beta1-adrenoceptor. 相似文献
63.
Emilia Bialopiotrowicz Bozena Kuzniewska Neli Kachamakova-Trojanowska Maria Barcikowska Jacek Kuznicki Urszula Wojda 《Neurobiology of aging》2011,32(12):2319
Cell cycle (CC) reactivation in neurons seems to underlie the development of Alzheimer's disease (AD). We analyzed whether CC alterations can be detected in immortalized lymphocytes from patients with the sporadic and the familial form of AD (SAD and FAD). Real-time polymerase chain reaction (PCR)-arrays, immunoblotting, and flow cytometry demonstrated differences in the regulation of G1/S phases between SAD lymphocytes and cells from nondemented subjects, as well as between SAD and FAD cells. SAD compared to FAD lymphocytes showed differences in expression profiles of the 90 CC genes, and a marked increase in the level of the p21 protein, which promotes G1-arrest. Accordingly, SAD but not FAD cells had a prolonged G1-phase. γ-secretase inhibition did not change the CC profiles of the cell lines. These data show that SAD involves a prolongation of the G1 phase driven by p21 pathway, which is not activated in FAD cells. Thus, the mechanism in SAD differs from FAD. Moreover, disturbances of the CC in lymphocytes have a potential diagnostic value. 相似文献
64.
Cheryl Clark Kathleen Good Lesley Jezierny Melissa Macpherson Brian Wilson Urszula Chajewska 《J Am Med Inform Assoc》2008,15(1):36-39
The Clinical Language Understanding group at Nuance Communications has developed a medical information extraction system that combines a rule-based extraction engine with machine learning algorithms to identify and categorize references to patient smoking in clinical reports. The extraction engine identifies smoking references; documents that contain no smoking references are classified as UNKNOWN. For the remaining documents, the extraction engine uses linguistic analysis to associate features such as status and time to smoking mentions. Machine learning is used to classify the documents based on these features. This approach shows overall accuracy in the 90s on all data sets used. Classification using engine-generated and word-based features outperforms classification using only word-based features for all data sets, although the difference gets smaller as the data set size increases. These techniques could be applied to identify other risk factors, such as drug and alcohol use, or a family history of a disease. 相似文献
65.
Urszula Malinowska Hubert Klekowicz Andrzej Wakarow Szymon Niemcewicz Piotr J. Durka 《Neuroinformatics》2009,7(4):245-253
We present an open system for sleep staging, based explicitly on the criteria used in visual EEG analysis. Slow waves, theta
and alpha waves, sleep spindles and K-complexes are parameterized in terms of time duration, amplitude, and frequency of each
waveform by means of the matching pursuit algorithm. It allows the detection of these structures using mostly the criteria
from visual EEG analysis. For example, within this framework for the first time we compute directly the relative duration
of slow waves, which is a basic parameter in recognition of deep sleep stages. Performance of the system is evaluated on 20
polysomnographic recordings, scored by experienced encephalographers. Seven recordings were scored by more than one expert.
Proposed system gives concordance with visual staging close to the inter-expert concordance. The algorithm is implemented
in a user-friendly software system for display and analysis of polysomnographic recordings, freely available with complete
source code from . 相似文献
66.
David S. Hydock Urszula T. Iwaniec Russell T. Turner Chia-Ying Lien Brock T. Jensen Traci L. Parry Carole M. Schneider Reid Hayward 《Pathophysiology》2008,15(4):253-259
A common treatment option for many breast and prostate cancer patients is the use of a luteinizing hormone-releasing hormone agonist such as goserelin acetate (GA) which reduces sex hormone levels. This treatment, however, is associated with bone degeneration, and exercise has been suggested as a means of preventing this side effect. Little is known about the effects of low intensity, low volume exercise on GA-induced bone loss. The purpose of this study, therefore, was to investigate the effects of voluntary wheel running on bone architecture in growing male (M) and female (F) rats receiving GA treatment. Rats received an 8-week GA treatment or placebo (CON) and were either housed in cages equipped with voluntary running wheels (WR) or remained sedentary (SED) in standard cages throughout the experimental period. Following treatments, tibiae were excised and analyzed for cortical bone (cross-sectional volume, cortical volume, marrow volume, cortical thickness) and cancellous bone (bone volume/total volume, trabecular number, trabecular thickness, trabecular spacing) using micro-computed tomography. Treatment with GA resulted in a significant reduction in running wheel distances in both sexes throughout the study period (P < 0.05). GA treatment had no effect on cortical bone architecture in neither sex (P > 0.05). Cancellous bone degeneration, however, was observed in M and F SED + GA (P < 0.05). No significant differences were observed in M WR + GA animals in bone volume/total volume, trabecular number and trabecular spacing when compared to M SED + CON (P > 0.05). In F WR + GA, trabecular thickness did not differ from that of F SED + CON (P > 0.05), and trabecular spacing was found to be significantly lower than F SED + GA (P < 0.05). The current report indicates that 8 weeks of GA treatment promotes cancellous bone degeneration, and voluntary wheel running provides no clear osteoprotection in growing male and female rats. 相似文献
67.
68.
The skeleton is a frequent localization of cancer metastases. The method of choice in their diagnostics is scintigraphy, but at high sensitivity, it is characterized by limited diagnostic specificity. Discussed are the possibilities of using the examination of some tumor markers as well as biochemical factors of the resorption and bone formation process in bone metastases diagnostics. At the present stage, it can be found that the studies of such factors introduce a number of additional significant information, but they cannot fully replace bone scan. 相似文献
69.
Russell T. Turner Stephen A. Martin Urszula T. Iwaniec 《Current osteoporosis reports》2018,16(2):95-104
Purpose of Review
Mesenchymal stem cells (MSCs) located in the bone marrow have the capacity to differentiate into multiple cell lineages, including osteoblast and adipocyte. Adipocyte density within marrow is inversely associated with bone mass during aging and in some pathological conditions, contributing to the prevailing view that marrow adipocytes play a largely negative role in bone metabolism. However, a negative association between marrow adipocytes and bone balance is not universal. Although MAT levels appear tightly regulated, establishing the precise physiological significance of MAT has proven elusive. Here, we review recent literature aimed at delineating the function of MAT.Recent Findings
An important physiological function of MAT may be to provide an expandable/contractible fat depot, which is critical for minimization of energy requirements for sustaining optimal hematopoiesis. Because the energy requirements for storing fat are negligible compared to those required to maintain hematopoiesis, even small reductions in hematopoietic tissue volume to match a reduced requirement for hematopoiesis could represent an important reduction in energy cost. Such a physiological function would require tight coupling between hematopoietic stem cells and MSCs to regulate the balance between MAT and hematopoiesis. Kit-ligand, an important regulator of proliferation, differentiation, and survival of hematopoietic cells, may function as a prototypic factor coupling MAT and hematopoiesis.Summary
Crosstalk between hematopoietic and mesenchymal cells in the bone marrow may contribute to establishing the balance between MAT levels and hematopoiesis.70.
Andrzej Eljaszewicz Katarzyna Kleina Kamil Grubczak Urszula Radzikowska Paula Zembko Paulina Kaczmarczyk Marlena Tynecka Karolina Dworzanczyk Beata Naumnik Marcin Moniuszko 《Stem cell reviews》2018,14(5):686-693
IgA nephropathy (IgAN) is recognized as most frequent form of primary glomerulonephritis worldwide. IgAN is associated with renal degradation occurring due to irreversible pathological changes leading to glomerulosclerosis and interstitial fibrosis. It remains poorly understood whether and to what extent these changes are followed by the activation of regenerative mechanisms. Therefore, in this study we aimed to evaluate regenerative potential of IgAN patients by quantitating the frequencies of several stem cell types, namely circulating very small embryonic-like stem cells (VSELs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs) as well as different monocyte subsets with varying maturation and angiopoietic potential. Moreover, we analyzed whether changes in stem cell and monocyte frequencies were related to alterations of several chemotactic factors (stromal derived-factor (SDF-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)) and a marker of monocyte/macrophage activation, namely soluble form of CD163 receptor (sCD163). We showed that IgAN patients presented with enhanced levels of VSELs, but not other stem cell types. We also demonstrated significantly elevated numbers of intermediate monocytes known for their M2-like properties as well as high angiopoietic potential and CD163 expression. This finding was accompanied by detection of elevated sCD163 plasma levels in IgAN patients. Taking together, we demonstrated here that IgAN is associated with selective mobilization of VSELs and increased maturation of monocytes towards M2-like and angiopoietic phenotype. These findings contribute to better understanding of the role of regenerative mechanisms in the pathogenesis of chronic inflammation in the course of IgAN. 相似文献