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41.
Understanding the difference between the development of a productive T‐cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self‐serum and orally introduced antigens. It is generally toleragenic. The current view is that this outcome reflects the failure of ‘immunogenic’ dendritic cells to relocate to the T‐cell zone of the secondary lymphoid tissues. Here, using a peptide/I‐Ek tetramer and antibodies to stain splenic sections, we showed that antigen‐specific T cells were activated in the spleen within hours of injection or feeding of protein. The activated T cells were found to be located at the T–B junction, the bridging zone and the B‐cell area, interacting directly with B cells. In addition, B cells gain the ability to present antigen. Our results suggest a way for T cells to be stimulated by blood‐borne antigen presented by naïve B cells, a potential mechanism of tolerance induction. 相似文献
42.
A rapid method of genomic array analysis of scaffold/matrix attachment regions (S/MARs) identifies a 2.5-Mb region of enhanced scaffold/matrix attachment at a human neocentromere
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Human neocentromeres are fully functional centromeres that arise at previously noncentromeric regions of the genome. We have tested a rapid procedure of genomic array analysis of chromosome scaffold/matrix attachment regions (S/MARs), involving the isolation of S/MAR DNA and hybridization of this DNA to a genomic BAC/PAC array. Using this procedure, we have defined a 2.5-Mb domain of S/MAR-enriched chromatin that fully encompasses a previously mapped centromere protein-A (CENP-A)-associated domain at a human neocentromere. We have independently verified this procedure using a previously established fluorescence in situ hybridization method on salt-treated metaphase chromosomes. In silico sequence analysis of the S/MAR-enriched and surrounding regions has revealed no outstanding sequence-related predisposition. This study defines the S/MAR-enriched domain of a higher eukaryotic centromere and provides a method that has broad application for the mapping of S/MAR attachment sites over large genomic regions or throughout a genome. 相似文献
43.
The ubiquitin-like protein, Nedd8, covalently modifies members of the Cullin family. Cullins are the major components of a series of ubiquitin ligases that control the degradation of a broad range of proteins. We found that Nedd8 modifies Cul1 in Drosophila. In Drosophila Nedd8 and Cul1 mutants, protein levels of the signal transduction effectors, Cubitus interruptus (Ci) and Armadillo (Arm), and the cell cycle regulator, Cyclin E (CycE), are highly accumulated, suggesting that the Cul1-based SCF complex requires Nedd8 modification for the degradation processes of Ci, Arm, and CycE in vivo. We further show that two distinct degradation mechanisms modulating Ci stability in the developing eye disc are separated by the morphogenetic furrow (MF) in which retinal differentiation is initiated. In cells anterior to the MF, Ci proteolytic processing promoted by PKA requires the activity of the Nedd8-modified Cul1-based SCF(Slimb) complex. In posterior cells, Ci degradation is controlled by a mechanism that requires the activity of Cul3, another member of the Cullin family. This posterior Ci degradation mechanism, which partially requires Nedd8 modification, is activated by Hedgehog (Hh) signaling and is PKA-independent. 相似文献
44.
Identification of clinically relevant viridans group streptococci by sequence analysis of the 16S-23S ribosomal DNA spacer region 总被引:6,自引:0,他引:6
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The feasibility of sequence analysis of the 16S-23S ribosomal DNA (rDNA) intergenic spacer (ITS) for the identification of clinically relevant viridans group streptococci (VS) was evaluated. The ITS regions of 29 reference strains (11 species) of VS were amplified by PCR and sequenced. These 11 species were Streptococcus anginosus, S. constellatus, S. gordonii, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, and S. uberis. The ITS lengths (246 to 391 bp) and sequences were highly conserved among strains within a species. The intraspecies similarity scores for the ITS sequences ranged from 0.98 to 1.0, except for the score for S. gordonii strains. The interspecies similarity scores for the ITS sequences varied from 0.31 to 0.93. Phylogenetic analysis of the ITS regions revealed that evolution of the regions of some species of VS is not parallel to that of the 16S rRNA genes. One hundred six clinical isolates of VS were identified by the Rapid ID 32 STREP system (bioMérieux Vitek, Marcy l'Etoile, France) and by ITS sequencing, and the level of disagreement between the two methods was 18% (19 isolates). Most isolates producing discrepant results could be unambiguously assigned to a specific species by their ITS sequences. The accuracy of using ITS sequencing for identification of VS was verified by 16S rDNA sequencing for all strains except strains of S. oralis and S. mitis, which were difficult to differentiate by their 16S rDNA sequences. In conclusion, identification of species of VS by ITS sequencing is reliable and could be used as an alternative accurate method for identification of VS. 相似文献
45.
Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. 总被引:1,自引:1,他引:1
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K. P. Burton L. M. Buja A. Sen J. T. Willerson K. R. Chien 《The American journal of pathology》1986,124(2):238-245
Alterations in triacylglycerol and phospholipid metabolism are known to occur during the evolution of myocardial ischemic injury. The purpose of this study was to explore potential relationships between the accumulation of arachidonic acid and other fatty acids, the accumulation of triacylglycerol, and the progression of myocardial injury. Measurements of the fatty acid levels in triacylglycerol, unesterified fatty acids, and calcium content were correlated with myocardial function during ischemia and ischemia with reflow in an isolated perfused rat heart preparation. After 10 minutes of ischemia in this model, myocardial dysfunction was reversible, with recovery of left ventricular +dP/dt to 82.0% +/- 4.8% of control values upon reperfusion. Hearts did not recover with reperfusion after 30 minutes of ischemia and displayed a significant increase in tissue calcium content. A significant, nearly threefold increase in the arachidonic acid content of triacylglycerol was found after 10 minutes of ischemia and continued to increase with longer periods of ischemia and reflow. Other fatty acids also showed increased levels in triacylglycerol. The time course of accumulation of unesterified arachidonic acid paralleled the loss of myocardial function. Levels of free arachidonic acid were (in nanomoles per gram wet weight) 11.1 +/- 2.1 (SEM) for control hearts, 17.3 +/- 1.9 after 10 minutes of ischemia, and 38.4 +/- 2.5 after 30 minutes of ischemia. Increases in other free fatty acids contributed to a significant increase in total free fatty acid accumulation after 30 minutes of ischemia. Thus, the content of arachidonic and other fatty acids in triacylglycerol was found to increase early during ischemia, and a major increase in free arachidonic and other unesterified fatty acids occurred after a longer period of ischemia. These findings are consistent with an initial reincorporation of free fatty acids into triacylglycerol after release from membrane phospholipids, suggesting that membrane fatty acids may be a major source of triacylglycerol that accumulates in ischemic myocardium. In addition, these results suggest that a major increase in free fatty acids during ischemia and ischemia with reflow correlates temporally with the development of severe contractile dysfunction and accumulation of calcium in the heart. 相似文献
46.
Shyh Ren Chiang Hung Jen Tang Ping Chin Chang Kuo Chen Cheng Wen Chien Ko Chung Hua Chen Yin Ching Chuang 《Journal of microbiology, immunology, and infection》2007,40(2):123-133
BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections. 相似文献
47.
Mao-Tsair Lin Yin-Hsiu Chien Shyh-Dar Shyur Li-Hsin Huang Yi-Chi Chiang Da-Chin Wen Pei-Hsuan Liang Hwai-Chih Yang 《Annals of allergy, asthma & immunology》2006,96(5):744-748
BACKGROUND: X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location. OBJECTIVES: To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years. METHODS: Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed. RESULTS: The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members. CONCLUSIONS: This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma. 相似文献
48.
Jo BJ Chung TS Lee MS Joo JY Ebert W Weinmann HJ Chien D Laub G 《Yonsei medical journal》1999,40(5):413-419
The purpose of this study was to compare the image quality of 3D-TOF MR angiography (MRA) using Gadomer-17 with that using Gd-DTPA in a flow phantom model, and to present preliminary data about the proper dose concentration of Gadomer-17. In the visual analysis of vessel conspicuity, we compared the quality of pre- and post-contrast MIP images. For quantitative analysis, the signal intensities were measured in the axial base 3D-TOF images, and then the relative contrast enhancement was calculated. The results of our studies were that: 1. Maximal signal intensities were obtained at 1 mmol/L of Gadomer-17 and 4 mmol/L of Gd-DTPA. 2. Flow-related signal loss was decreased by Gd-DTPA proportional to the concentration, but Gadomer-17 did not show such a dose accumulative effect. In conclusion, after comparing the results of Gd-DTPA, it was clear that improved MRA images and higher signal intensities of vessels were obtained when lower concentrations of Gadomer-17 were used. 相似文献
49.
Transcriptome analysis in blastocyst hatching by cDNA microarray 总被引:1,自引:0,他引:1
Chen HW Chen JJ Yu SL Li HN Yang PC Su CM Au HK Chang CW Chien LW Chen CS Tzeng CR 《Human reproduction (Oxford, England)》2005,20(9):2492-2501
BACKGROUND: Hatching is an important process for early embryo development, differentiation and implantation. However, little is known about its regulatory mechanisms. By integrating the technologies of RNA amplification and cDNA microarrays, it has become possible to study the gene expression profile at this critical stage. METHODS: Pre-hatched and hatched ICR mouse embryos (25 blastocysts in each group were used in the triplicate experiments) were collected for RNA extraction, amplification, and microarray analysis (the mouse cDNA microarray, 6144 genes, including expressed sequence tags). RESULTS: According to cDNA microarray data, we have identified 85 genes that were expressed at a higher level in hatched blastocyst than in pre-hatched blastocysts. In this study, 47 hatching-related candidate genes were verified via re-sequencing. Some of these genes have been selected and confirmed by real-time quantitative RT-PCR. These hatching-specific genes were also expressed at a lower level in the delayed growth embryos (morula or blastocyst without hatching at day 6 post hCG). These genes included: cell adhesion and migration molecules [E-cadherin, neuronal cell adhesion molecule (NCAM), lectin, galactose binding, soluble 7 (Lgals7), vanin 3 and biglycan], epigenetic regulators (Dnmt1, and SIN3 yeast homolog A), stress response regulators (heme oxygenase 1) and immunoresponse regulators [interleukin (IL)-2-inducible T-cell kinase, IL-4R, interferon-gamma receptor 2, and neurotrophin]. The immunostaining of E-cadherin and NCAM showed strong and specific localization in hatched blastocyst. CONCLUSIONS: This work provides important information for studying the mechanisms of blastocyst hatching and implantation. These hatching-specific genes may have potential as new drug targets for controlling fertility. 相似文献
50.
Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins 总被引:1,自引:0,他引:1
Takaki S Sauer K Iritani BM Chien S Ebihara Y Tsuji K Takatsu K Perlmutter RM 《Immunity》2000,13(5):599-609
Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling. 相似文献