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31.
ABEL TRUJILLO-OCAMPO HYUN-WOO CHO AMANDA C. HERRMANN WILFREDO RUIZ-VAZQUEZ ANDREW B. THORNTON HONG HE DAN LI MARIAM A. QAZILBASH QING MA STEVEN A. PORCELLI ELIZABETH J. SHPALL JEFFREY MOLLDREM JIN S. IM 《Cytotherapy》2018,20(8):1089-1101
Background aims
CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT.Methods
Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks.Results
The single antigenic stimulation reliably expanded iNK T cells to an average of 2.8?×?107 per 5?×?108 PBMCs in an average purity of 98.8% in 2 weeks (N?=?24). The expanded iNK T cells contained a significantly higher level of CD4+ and central memory phenotype (CD45RA?CD62L+) compared with freshly isolated iNK T cells, and maintained their ability to produce both Th-1 (interferon [IFN]γ and tumor necrosis factor [TNF]α) and Th-2 type cytokines (interleukin [IL]-4, IL-5 and IL-13) upon antigenic stimulation or stimulation with Phorbol 12-myristate 13-acetate/ionomycin. Interestingly, expanded iNK T cells were highly autoreactive and produced a Th-2 polarized cytokine production profile after being co-cultured with dendritic cells alone without exogenous agonist glycolipid antigen. Lastly, expanded iNK T cells suppressed conventional T-cell proliferation and ameliorated xenograft GVHD (hazard ratio, 0.1266; P < 0.0001).Conclusion
We have demonstrated a feasible approach for obtaining ex vivo expanded, highly enriched human iNK T cells for use in adoptive cell therapy to prevent GVHD in ASCT. 相似文献32.
Robin IM Dunbar 《BMC biology》2007,5(1):21-3
The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social
brain" hypothesis) is now widely accepted. Some of the evidence to support this comes from the fact that species that live
in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20) add significantly to our appreciation of this process by showing that there are striking differences between the two
sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative) is related most closely
to neocortex volume, but male sociality (which is more competitive and combative) is more closely related to subcortical units
(notably those associated with emotional responses). Thus different brain units have responded to different selection pressures. 相似文献
33.
Reichler IM Welle M Sattler U Jöchle W Roos M Hubler M Barth A Arnold S 《Theriogenology》2007,67(6):1134-1142
Ovariectomy interrupts the regulatory loop in the hypothalamus-pituitary-gonad axis, leading to a several-fold increase in gonadotropin levels. This rise in hormonal secretion may play a causal role in ovariectomy-related urinary incontinence. The purpose of this study was to examine the effect of ovariectomy in bitches on the expression of GnRH- and LH-receptors in the lower urinary tract, and assess the relationship between receptor expression and plasma gonadotropin concentrations. Plasma gonadotropins were measured in 37 client-owned bitches. Biopsies were harvested from the mid-ventral bladder wall in all dogs, and from nine further locations within the lower urinary tract in 17 of the 37 animals. Messenger RNA of the LH and GnRH receptors was quantified using RT-PCR with the TaqMan Universal PCR Master Mix. Gonadotropins were measured with a canine-specific FSH-immunoradiometric assay and LH-radioimmunoassay. The hierarchical mixed ANOVA model using MINITAB, Mann-Whitney U-test, unpaired means comparison and linear regressions using StatView were applied for statistical analyses. Messenger RNA for both receptors was detected in all biopsy samples. Age was negatively correlated to mRNA expression of the LH and the GnRH receptors. A relationship between the mRNA values and the plasma gonadotropin concentrations was not established. Evaluation of results within each of the biopsy locations revealed greater LH-receptor expression in the proximal second quarter of the urethra in spayed bitches than in intact bitches (P=0.0481). Increased mRNA expression of LH receptors in this location could possibly play a role in the decrease in closing pressure of the urethra following ovariectomy. 相似文献
34.
Effect of self-association on the structural organization of partially folded proteins: inactivated actin 总被引:1,自引:0,他引:1 下载免费PDF全文
IM Kuznetsova AG Biktashev SY Khaitlina KS Vassilenko KK Turoverov VN Uversky 《Biophysical journal》1999,77(5):2788-2800
The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules. 相似文献
35.
Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol 总被引:1,自引:0,他引:1
The effects of alfaxalone and propofol on neonatal vitality were studied in 22 bitches and 81 puppies after their use as anesthetic induction agents for emergency cesarean section. After assessment that surgery was indicated, bitches were randomly allocated to receive alfaxalone 1 to 2 mg/kg body weight or propofol 2 to 6 mg/kg body weight for anesthetic induction. Both drugs were administered intravenously to effect to allow endotracheal intubation, and anesthesia was maintained with isoflurane in oxygen. Neonatal vitality was assessed using a modified Apgar score that took into account heart rate, respiratory effort, reflex irritability, motility, and mucous membrane color (maximum score = 10); scores were assigned at 5, 15, and 60 minutes after delivery. Neither the number of puppies delivered nor the proportion of surviving puppies up to 3 months after delivery differed between groups. Anesthetic induction drug and time of scoring were associated with the Apgar score, but delivery time was not. Apgar scores in the alfaxalone group were greater than those in the propofol group at 5, 15, and 60 minutes after delivery; the overall estimated score difference between the groups was 3.3 (confidence interval 95%: 1.6–4.9; P < 0.001). In conclusion, both alfaxalone and propofol can be safely used for induction of anesthesia in bitches undergoing emergency cesarean section. Although puppy survival was similar after the use of these drugs, alfaxalone was associated with better neonatal vitality during the first 60 minutes after delivery. 相似文献
36.
Prototype of a Fully Automated Device for Determination of Bacterial Antibiotic Susceptibility in the Clinical Laboratory 总被引:10,自引:0,他引:10 下载免费PDF全文
A completely automated system for the performance of antibiotic susceptibility tests in the clinical laboratory is described. With a modicum of personnel involvement, data on 40 specimens tested against 13 antibiotics are obtained every hour after an initial 3-hr period. The step by step explanation of the functioning of this prototype system, based on a thoroughly tested manual model, is presented. The system compares well with the standard diffusion test and has a potential for application to other endeavors of the clinical microbiology laboratory with a comparable saving in time and labor. 相似文献
37.
The characteristics of purified HL60 tuftsin receptors 总被引:1,自引:0,他引:1
Nancy J. Bump Victor A. Najjar Judith Reichler 《Molecular and cellular biochemistry》1990,92(1):77-84
Summary The purification and characteristics of purified HL60 tuftsin receptors are described. Purification was accomplished by affinity chromatography similar to that described earlier, wherein a tuftsin analog Thr-LysPro-Pro-Arg, is covalently linked at the N group to a solid support. The receptor consists presumably of two subunits approximately 66 KDa and 57 KDa. The dissociation constant of the receptor complex is 4.7 × 10–8 M with 5 × 104 receptors per cell. It can form oligomers with an Mr of about 560 KDa suggesting an octomeric structure, assuming the same number of each subunit is associated.Abbreviations CHAPS
3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
- DCC
Dicyclohexylcarbodiimide
- DMSO
Dimethylsulfoxide
- DSS
Disuccinimidylsuberate
- FCS
Fetal Calf Serum
- HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic Acid
- MMP
Macrophage/Monocyte and Polymorphonuclear granulocytes
- Mr
Relative Molecular mass
- NaDodSO4
Sodium Dodecyl Sulfate
- PEG
Polyethylene Glycol
- SP
Sucrose Phosphate buffer
- TFMS
Trifluoromethanesulfonic Acid 相似文献
38.
The abundance of plant nucleolin mRNA is regulated during de-etiolation by phytochrome. A close correlation between the mRNA abundance of nucleolin and mitosis has also been previously reported. These results raised the question of whether the effects of light on nucleolin mRNA expression were a consequence of light effects on mitosis. To test this we compared the kinetics of light-mediated increases in cell proliferation with that of light-mediated changes in the abundance of nucleolin mRNA using plumules of dark-grown pea (Pisum sativum) seedlings. These experiments show that S-phase increases 9 h after a red light pulse, followed by M-phase increases in the plumule leaves at 12 h post-irradiation, a time course consistent with separately measured kinetics of red light-induced increases in the expression of cell cycle-regulated genes. These increases in cell cycle-regulated genes are photoreversible, implying that the light-induced increases in cell proliferation are, like nucleolin mRNA expression, regulated via phytochrome. Red light stimulates increases in the mRNA for nucleolin at 6 h post-irradiation, prior to any cell proliferation changes and concurrent with the reported timing of phytochrome-mediated increases of rRNA abundance. After a green light pulse, nucleolin mRNA levels increase without increasing S-phase or M-phase. Studies in animals and yeast indicate that nucleolin plays a significant role in ribosome biosynthesis. Consistent with this function, pea nucleolin can rescue nucleolin deletion mutants of yeast that are defective in rRNA synthesis. Our data show that during de-etiolation, the increased expression of nucleolin mRNA is more directly regulated by light than by mitosis. 相似文献
39.
Michel E Feldmann SK Kowalewski MP Rohrer Bley C Boos A Guscetti F Reichler IM 《BMC veterinary research》2012,8(1):72
ABSTRACT: BACKGROUND: Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffinembedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. RESULTS: The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p =0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. CONCLUSIONS: Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding. 相似文献
40.
Rachel IM van Haaften Blanche Schroen Ben JA Janssen Arie van Erk Jacques JM Debets Hubert JM Smeets Jos FM Smits Arthur van den Wijngaard Yigal M Pinto Chris TA Evelo 《BMC bioinformatics》2006,7(1):200-15