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111.
With the continuing increase in the number of severely immunocompromised patients, hospitals are faced with the growing problem of invasive aspergillosis and other opportunistic fungal infections. Since treatment of these infections are difficult and outcome is often fatal, preventive measures are of major importance in the control of invasive filamentous fungal infections. Until recently, inhalation of airborne conidia was believed to be the primary route of acquiring Aspergillus infection. Despite the fact, that efforts to filter the hospital air has led to a reduction of airborne conidia paralleled by a decrease in the frequency of invasive infections, the correlation between the concentration of Aspergillus conidia in hospital air and the risk of invasive infections remains unclear. Furthermore, alternative modes of transmission may exist and should be recognized and investigated. The discovery of hospital water as a potential source of Aspergillus fumigatus and other filamentous fungi may suggest a new route for the transmission of invasive filamentous fungal infections. Epidemiological studies, based on molecular characterization and comparisons of fungal isolates recovered from patients and environment, are needed to expand our understanding of these alternative routes of transmission. 相似文献
112.
Femtomole quantitation of 7-ethyl-10-hydroxycamptothecine (SN-38) in plasma samples by reversed-phase high-performance liquid chromatography 总被引:2,自引:0,他引:2
de Bruijn P de Jonge MJ Verweij J Loos WJ Nooter K Stoter G Sparreboom A 《Analytical biochemistry》1999,269(1):174-178
7-Ethyl-10-hydroxycamptothecine (SN-38) is the active metabolite of the topoisomerase I inhibitor and antineoplastic agent, irinotecan (CPT-11). Here, we present a new and sensitive reversed-phase high-performance liquid chromatographic method for the determination of SN-38 in human plasma samples. Sample pretreatment involves a protein precipitation of 1-mL samples with 2 mL of acetonitrile, followed by a one-step solvent extraction with 5 mL of chloroform, with camptothecine used as internal standard. Chromatographic separation was achieved on an analytical column packed with Hypersil ODS material (100 x 4.6 mm i.d., 5 microm P.S.), and isocratic elution with a mixture of acetonitrile:0.1 M ammonium acetate containing 10 mM tetrabutylammonium sulfate (23:77, v/v), pH 5.3 (hydrochloric acid). The column effluent was monitored at excitation and emission wavelengths of 380 and 556 nm, respectively. The limit of quantitation of the method presented was at the low femtomole level ( approximately 8.4 fmol; equivalent to 5 pg/mL), with the standard curves being linear over nearly three orders of magnitude. Intraassay precision was <9%, while interassay variations were between 2 and 5%. The extraction efficiency was concentration independent and averaged 88.0 +/- 14.3% (mean +/- standard deviation; n = 59). The described method will be used in future studies to assess the extent of enterohepatic recirculation of SN-38 in cancer patients following intravenous CPT-11 treatment. 相似文献
113.
114.
Obtaining informed consent for using blood samples in research is mandatory. However, sometimes no consent is obtained for analysis of identifiable blood samples in a second study. As a result, a moral dilemma raises in case a possibly pathogenic mutation is found. Should the involved person be informed that such a mutation has been detected? We present a case in which this problem occurred and discuss arguments for and against information disclosure. 相似文献
115.
Bayley JP van Rietschoten JG Bakker AM van Baarsen L Kaijzel EL Wierenga EA van der Pouw Kraan TC Huizinga TW Verweij CL 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(5):2349-2353
A number of reports have described the monoallelic expression of murine cytokine genes. Here we describe the monoallelic expression of the human IL-1alpha gene in CD4+ T cells. Analysis of peripheral blood T cell clones derived from healthy individuals revealed that the IL-1alpha gene shows predominantly monoallelic expression. Monoallelic expression was observed in Th0, Th1, and Th2 cell clones. In addition, we demonstrate monoallelic expression in T cell clones from rheumatoid arthritis patients derived from synovial fluid of the knee joint, suggesting that the occurrence of this phenomenon is not different from that in clones derived from healthy individuals. The finding of monoallelic expression of a cytokine gene in human CD4+ T cell clones provides evidence for allele-specific silencing/activation as another layer of regulation of IL-1alpha gene expression. 相似文献
116.
van Rietschoten JG Smits HH Westland R Verweij CL den Hartog MT Wierenga EA 《Immunogenetics》2000,51(1):30-36
The interleukin-12 receptor (IL-12R) is composed of two subunits, referred to as β1 and β2. Both chains are necessary for
high-affinity IL-12 binding and signalling, although only the IL-12Rβ2 chain contains the intracellular tyrosine residues
responsible for STAT4 activation. This study presents the intron-exon organization of the human IL-12Rβ2-chain gene. Polymerase
chain reaction (PCR) primers designed across the cDNA (U46198) were used to trace introns, by comparing PCR product sizes
obtained using cDNA and genomic DNA as templates. PCR products spanning introns were sequenced to determine the exact splice
sites and flanking regions. The coding region of the gene was found to consist of 15 exons and 14 introns. All intron-exon
boundaries are consistent with the consensus sequence for splice junctions (5′ GT/AG 3′). Comparison of the intron-exon organization
with the human GCSFR gene indicated a remarkably well conserved genomic organization between these two class I cytokine receptors. Interestingly,
we identified an alternatively spliced mRNA, encoding a putative, truncated protein, lacking all signalling potential.
Received: 21 July 1999 / Revised: 2 September 1999 相似文献
117.
Smeeta Shrestha Yang Sun Thomas Lufkin Petra Kraus Yuzuan Or Yenni A. Garcia Naihsuan Guy Paola Ramos Marc B. Cox Fiona Tay Valerie CL Lin 《International journal of biological sciences》2015,11(4):434-447
Tetratricopeptide repeat domain 9A (TTC9A) is a target gene of estrogen and progesterone. It is over-expressed in breast cancer. However, little is known about the physiological function of TTC9A. The objectives of this study were to establish a Ttc9a knockout mouse model and to study the consequence of Ttc9a gene inactivation. The Ttc9a targeting vector was generated by replacing the Ttc9a exon 1 with a neomycin cassette. The mice homozygous for Ttc9a exon 1 deletion appear to grow normally and are fertile. However, further characterization of the female mice revealed that Ttc9a deficiency is associated with greater body weight, bigger thymus and better mammary development in post-pubertal mice. Furthermore, Ttc9a deficient mammary gland was more responsive to estrogen treatment with greater mammary ductal lengthening, ductal branching and estrogen target gene induction. Since Ttc9a is induced by estrogen in estrogen target tissues, these results suggest that Ttc9a is a negative regulator of estrogen function through a negative feedback mechanism. This is supported by in vitro evidence that TTC9A over-expression attenuated ERα activity in MCF-7 cells. Although TTC9A does not bind to ERα or its chaperone protein Hsp90 directly, TTC9A strongly interacts with FKBP38 and FKBP51, both of which interact with ERα and Hsp90 and modulate ERα activity. It is plausible therefore that TTC9A negatively regulates ERα activity through interacting with co-chaperone proteins such as FKBP38 and FKBP51. 相似文献
118.
Germana B Rona Natalia P Almeida Gilson C Santos Jr Tatiana KS Fidalgo Fabio CL Almeida Elis CA Eleutherio Anderson S Pinheiro 《Journal of cellular biochemistry》2019,120(4):5377-5385
NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein-dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming. 相似文献
119.
Chuanchuan Li Xia Meng Zhen Zhang Yanyan Wang Xiaomin Song Wenjia Wang Rongguang Zhang Yun Zhao Catherine CL Wong Zhaocai Zhou 《The EMBO journal》2015,34(23):2903-2920
RIG‐I is a well‐studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4‐Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG‐I. The p97 complex is able to directly bind both non‐ubiquitinated RIG‐I and the E3 ligase RNF125, promoting K48‐linked ubiquitination of RIG‐I at residue K181. Viral infection significantly strengthens the interaction between RIG‐I and the p97 complex by a conformational change of RIG‐I that exposes the CARDs and through K63‐linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG‐I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy. 相似文献
120.
Niels Grote Beverborg Niek Verweij IJsbrand T. Klip Haye H. van der Wal Adriaan A. Voors Dirk J. van Veldhuisen Ron T. Gansevoort Stephan J. L. Bakker Pim van der Harst Peter van der Meer 《PloS one》2015,10(4)