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101.
Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT. 相似文献
102.
Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells 总被引:9,自引:0,他引:9
Finstad HS; Kolset SO; Holme JA; Wiger R; Farrants AK; Blomhoff R; Drevon CA 《Blood》1994,84(11):3799-3809
Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation. 相似文献
103.
Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent. 相似文献
104.
Arrhythmogenic Evidence for Epicardial Adipose Tissue: Heart Rate Variability and Turbulence are Influenced by Epicardial Fat Thickness
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105.
106.
Erica L Johnson Hin Chu Siddappa Nagadenahalli Byrareddy Paul Spearman Rana Chakraborty 《Journal of the International AIDS Society》2015,18(1)
Introduction
Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been shown to be infected in vivo and sustain low levels of viral replication in vitro; however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined. The objective of this study is to define potential sites of viral assembly, accumulation and neutralization in HCs given the pivotal role of the placenta in preventing HIV-1 infection in the mother-infant dyad.Methods
Term placentae from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated by 3D confocal and electron microscopy. Colocalization R values (Pearson''s correlation) were quantified with colocalization module of Volocity 5.2.1. Replication kinetics and neutralization studies were evaluated using p24 ELISA.Results
We demonstrate that primary HCs assemble and sequester HIV-1BaL in intracellular VCCs, which are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP-1. Following infection, we observed HIV-1 accumulation in potentially acidic compartments, which stained intensely with Lysotracker-Red. Remarkably, these compartments are readily accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1-specific broadly neutralizing antibodies. In addition, broadly neutralizing antibodies (4E10 and VRC01) limited viral replication by HIV-1-infected HCs, which may be mediated by FcγRI.Conclusions
These findings suggest that placental HCs possess intrinsic adaptations facilitating unique sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral neutralization and/or antiretroviral drug entry in utero. 相似文献107.
108.
Marie-Luise Berres Karen Phaik Har Lim Tricia Peters Jeremy Price Hitoshi Takizawa Hélène Salmon Juliana Idoyaga Albert Ruzo Philip J. Lupo M. John Hicks Albert Shih Stephen J. Simko Harshal Abhyankar Rikhia Chakraborty Marylene Leboeuf Monique Beltr?o Sérgio A. Lira Kenneth M. Heym Bj?rn E. Clausen Venetia Bigley Matthew Collin Markus G. Manz Kenneth McClain Miriam Merad Carl E. Allen 《The Journal of experimental medicine》2015,212(2):281
109.
Paramita Chakraborty Satyajit Das Kaushik Banerjee Abhinaba Sinha Susmita Roy Mitali Chatterjee 《Immunopharmacology and immunotoxicology》2014,36(2):165-175
Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of immunosuppressive network are present in the tumor microenvironment suppress antitumor immunity by subverting Th1 response in tumor site and considered as a great obstacle for advancement of different cancer immunotherapeutic protocols. Till date, various pharmacological approaches have been explored to modulate the suppressive functions of MDSCs in vivo. The present study describes our endeavor to explore a possibility of eradicating MDSCs by the application of a copper chelate, namely copper N-(2-hydroxy acetophenone) glycinate (CuNG), previously found to be a potential immunomodulator that can elicit antitumorogenic Th1 response in doxorubicin-resistant EAC (EAC/Dox) bearing mice. Herein, we demonstrated that CuNG treatment could reduce Gr-1+CD11b+ MDSC accumulation in ascitic fluid and spleen of EAC/Dox tumor model. Furthermore, we found that CuNG mediated reduction in MDSCs is associated with induction of Th1 response and reduction in Treg cells. Moreover, we observed that CuNG could deplete MDSCs by inducing Fas-FasL mediated apoptotic cell death where death receptor Fas expression is enhanced in MDSCs and FasL is provided by activated T cells. However, MDSC expansion from bone marrow cells and their differentiation was not affected by CuNG. Altogether, these findings suggest that the immunomodulatory property of CuNG is attributed to, at least in part, by its selective cytotoxic action on MDSCs. So, this preclinical study unveils a new mechanism of regulating MDSC levels in drug-resistant cancer model and holds promise of translating the findings into clinical settings. 相似文献
110.
P. Chakraborty Banerjee Ren Ping Woo Sam Matthew Grayson Amrita Majumder R. K. Singh Raman 《Materials》2014,7(8):6092-6104
The protective performance of zeolite coating on AZ91D magnesium alloy was evaluated using potentiodynamic polarisation and electrochemical impedance spectroscopy (EIS) in 0.1 M sodium chloride solution (NaCl). Electrical equivalent circuit (EEC) was developed based upon hypothetical corrosion mechanisms and simulated to correspond to the experimental data. The morphology and the chemical nature of the coating were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Post corrosion morphologies of the zeolite coated and the uncoated AZ91D alloy were investigated using SEM. The corrosion resistance of the zeolite coated specimen was at least one order of magnitude higher than the uncoated specimen. 相似文献