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101.
Depressive illness is generally associated with cognitive impairment. Serotonergic selective antidepressant drugs, fluoxetine (FLX), sertraline (SER) and tianeptine (TIA), are claimed to have less or no effect on cholinergic system, the key system involved in memory. In the present study, these drugs were evaluated for their influence on cognitive behavior in both depressive and non-depressive animals. Depression was induced by two models, (i) 60 days social isolation of litter; and ii) by applying chronic unpredictable mild stress for 21 days. Depression in the rats was confirmed by behavioral despair test. Transfer latency on elevated plus maze and inflexion ratio in passive avoidance step through behavior were employed to assess learning and memory. The results indicated that administration of fluoxetine; sertraline and tianeptine attenuated the cognitive deficits observed in depressive rats. In non-depressive rats these drugs produced retention deficit, which was found to be parameter and model dependent. Data suggested that, FLX and SER (SSRI's) effectively attenuated the isolation-induced depression and cognitive deficit, whereas TIA (SSRE) produced better effect in stress-induced depressive conditions. It was concluded that behavioral profiles of fluoxetine, sertraline and tianeptine on cognition were model and parameter dependent. 相似文献
102.
NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4 总被引:34,自引:0,他引:34
Helbig G Christopherson KW Bhat-Nakshatri P Kumar S Kishimoto H Miller KD Broxmeyer HE Nakshatri H 《The Journal of biological chemistry》2003,278(24):21631-21638
103.
Bispecific and bifunctional monoclonal antibodies as second generation monoclonals, produced by conventional chemical or somatic methods, have proved useful in the immunodiagnosis and immunotherapy of cancer and other diseases. Recombinant antibodies produced by genetic engineering techniques have also become available for use in preclinical and clinical studies. Furthermore, through genetic engineering, it is possible to remove or add on key protein domains in order to create designer antibody molecules with two or more desired functions. This review summarizes the strategies for development of single chain variable fragment (scFv) bifunctional and bispecific antibodies. The advantages and disadvantages as well as the problems of generating the various bispecific and bifunctional antibody constructs are reported and discussed. Since conventionally prepared bispecific and bifunctional monoclonal antibodies have already shown promise in clinical trials and results from preclinical studies of recombinant bispecific antibodies are encouraging, clinical trials in humans of recombinant bispecific and bifunctional antibodies, as a new generation of biologicals, are likely to be the thrust in the next decade and beyond. 相似文献
104.
Giri R Selvaraj S Miller CA Hofman F Yan SD Stern D Zlokovic BV Kalra VK 《American journal of physiology. Cell physiology》2002,283(3):C895-C904
During normal aging and amyloid beta-peptide (Abeta) disorders such as Alzheimer's disease (AD), one finds increased deposition of Abeta and activated monocytes/microglial cells in the brain. Our previous studies show that Abeta interaction with a monolayer of normal human brain microvascular endothelial cells results in increased adherence and transmigration of monocytes. Relatively little is known of the role of Abeta accumulated in the AD brain in mediating trafficking of peripheral blood monocytes (PBM) across the blood-brain barrier (BBB) and concomitant accumulation of monocytes/microglia in the AD brain. In this study, we showed that interaction of Abeta(1--40) with apical surface of monolayer of brain endothelial cells (BEC), derived either from normal or AD individuals, resulted in increased transendothelial migration of monocytic cells (HL-60 and THP-1) and PBM. However, transmigration of monocytes across the BEC monolayer cultivated in a Transwell chamber was increased 2.5-fold when Abeta was added to the basolateral side of AD compared with normal individual BEC. The Abeta-induced transmigration of monocytes was inhibited in both normal and AD-BEC by antibodies to the putative Abeta receptor, receptor for advanced glycation end products (RAGE), and to the endothelial cell junction molecule, platelet-endothelial cell adhesion molecule-1 (PECAM-1). We conclude that interaction of Abeta with the basolateral surface of AD-BEC induces cellular signaling, promoting transmigration of monocytes from the apical to basolateral direction. We suggest that Abeta in the AD brain parenchyma or cerebrovasculature initiates cellular signaling that induces PBM to transmigrate across the BBB and accumulate in the brain. 相似文献
105.
Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial endothelial cell activation 总被引:4,自引:0,他引:4
To determine whether homocysteine(Hcy)-mediated activation of endocardial endothelial (EE) cells isameliorated by peroxisome proliferator-activated receptor (PPAR), weisolated EE cells from mouse endocardium. Matrix metalloproteinase(MMP) activity and intercellular adhesion molecule (ICAM)-1 in EE cellswere measured in the presence and absence of Hcy, and ciprofibrate (CF;PPAR- agonist) or 15-deoxy-12,14-prostaglandinJ2 (PGJ2; PPAR- agonist) by zymography andWestern blot analyses, respectively. Results suggest that Hcy-mediated MMP activation and ICAM-1 expression are ameliorated by CF and PGJ2. To test the hypothesis that Hcy competes with otherligands for binding to PPAR and -, we prepared cardiac nuclearextracts. Extracts were loaded onto an Hcy-cellulose affinity column.Bound proteins were eluted with CF and PGJ2. To determineconformational changes in PPAR upon binding to Hcy, we measured PPARfluorescence at 334 nm. Dose-dependent increase in PPAR fluorescencedemonstrated a primary binding affinity of 0.32 ± 0.06 µM. There wasdose-dependent quenching of PPAR fluorescence byfluorescamine-homocysteine (F-Hcy). PPAR- fluorescence quenching wasabrogated by the addition of CF but not by PGJ2. PPAR-fluorescence quenching was abrogated by the addition ofPGJ2 but not by CF. These results suggest that Hcy competeswith CF and PGJ2 for binding to PPAR- and -,respectively, indicating a role of PPAR in amelioration of Hcy-mediatedEE dysfunction. 相似文献
106.
In many remodeling tissues, such as the heart, collagen degradation to provide new integrin-binding sites is required for survival. However, complete loss of integrin signaling due to disconnection from extracellular matrix (ECM) leads to apoptosis and dilatation. To test the hypothesis that a mutation in type I collagen gene induces cardiomyopathy, we employed a metalloproteinase-resistant collagen mutant homozygous transgenic male (B6,129-Colla-1) and compared with age-sex matched wildtype C57BL/J6 control mice. At the age of 38-42 weeks, aortic and left ventricle (LV) pressure were measured. The LV wall thickness and diameter were measured by a digital micrometer. The levels of matrix metalloproteinase-2 (MMP-2) activity and cardiospecific tissue inhibitor of metalloproteinase-4 (TIMP-4) were measured by zymography and Western blot analyses, respectively. The levels of collagenolysis were measured by Western blot using anti-collagen antibody. In transgenic and wildtype mice, end-diastolic pressure (EDP) was 8.3 +/- 1.7 and 6.5 +/- 1.1 mmHg; LV diameter was 3.43 +/- 0.07 and 2.94 +/- 0.05 mm; wall thickness was 1.18 +/- 0.03 and 1.28 +/- 0.04 mm; end-diastolic wall stress was 600 +/- 158 and 347 +/- 49 dynes/cm(2), respectively. The increase in LV wall stress was associated with increased MMP-2 activity, increased collagenolysis, and decreased levels of TIMP-4. This leads to reduced elastic compliance in collagen mutant transgenic mice. The occurrence of cardiomyopathy in adult Colla-1 mice may be a significant confounding factor as it may be indicative of increased basal levels of ECM disruption. This phenotype is what would be expected if collagen degradation normally supplies integrin ligands during cardiac muscle remodeling. 相似文献
107.
Maiti M Das S Sen A Das A Kumar GS Nandi R 《Journal of biomolecular structure & dynamics》2002,20(3):455-464
Sanguinarine exhibits pH dependent structural equilibrium between iminium form (structure I) and alkanolamine form (structure II) with a pKa of 7.4 as revealed from spectrophotometric titration. The titration data show that the compound exists almost exclusively as structure I and structure II in the pH range 1 to 6 and 8.5 to 11, respectively. The interaction of structure I and structure II to several B-form natural and synthetic double and single stranded DNAs has been studied by spectrophotometric, spectrofluorimetric and circular dichroic measurements in buffers of pH 5.2 and pH 10.4 where the physicochemical properties of DNA remain in B-form structure. The results show that structure I bind strongly to all B-form DNA structures showing typical hypochromism and bathochromism of the alkaloid's absorption maximum, quenching of steady-state fluorescence intensity and perturbations in circular dichroic spectrum. The structure II does not bind to DNA, but in presence of large amount of DNA significant population of structure I is generated, which binds to DNA and forms a structure I-DNA intercalated complex. The nature and magnitude of the spectral pattern are very much dependent on the structure as well as base composition of each DNA. The generation of the structure I from structure II is significantly affected by increasing ionic strength of the medium. The conversion of structure II to structure I in presence of high concentration of DNA in solution is explained through formation of a binding equilibrium process between structure II and structure I-DNA intercalated complex. 相似文献
108.
Although it is well established that the processes of cellular proliferation and apoptosis are linked, the role of cell cycle regulators in T cell responses in vivo is not well understood. In recent years, tumor suppressor molecule p19(ARF) has emerged as a key cell cycle regulator important in cellular apoptosis against strong mitogenic stimuli. In this study, we compared the antigen-specific T cell responses between wild type (+/+) and p19(ARF)-deficient (p19-/-) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). p19-/- mice mounted a potent CD8 T cell response and the magnitude of expansion of LCMV-specific CD8 T cells was comparable to that of +/+ mice. Further, the clonal downsizing of the expanded virus-specific CD8 T cells and establishment of long-term T cell memory were minimally affected by p19(ARF) deficiency. Therefore, p19(ARF) function is not essential to regulate T cell responses following an acute viral infection. 相似文献
109.
Mutations affecting endocytosis, such as those in clathrin and dynamin, unexpectedly cause defects in cytokinesis in a number of organisms. To explore the relationship between endocytosis and cytokinesis, we used the relatively large cells of the transparent zebrafish embryo. Using fluorescent markers for fluid-phase as well as plasma membrane uptake, we demonstrate that cytokinesis involves furrow-specific endocytosis. Clathrin-coated pits are visible near the furrow in ultrathin sections, while immunolabeling demonstrates that clathrin and caveolin are localized to the cleavage furrow. Hence, it is likely that both clathrin- and caveolae-mediated endocytosis occurs at the furrow during cytokinesis. Dynamin II is also localized to the furrow and may mediate furrow-specific endocytosis. Treatment of embryos with chlorpromazine or with methyl-beta-cyclodextrin, both of which inhibit endocytosis, prevents the normal completion of cytokinesis. These data suggest that furrow-specific endocytosis is an integral part of cytokinesis. 相似文献
110.