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Marsh JC; Will AJ; Hows JM; Sartori P; Darbyshire PJ; Williamson PJ; Oscier DG; Dexter TM; Testa NG 《Blood》1992,79(12):3138-3144
We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. 相似文献
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Fuad S. Shihab Ali Olyaei Anne Wiland Kevin McCague Douglas J. Norman 《Clinical transplantation》2014,28(7):768-775
Tacrolimus exposure and renal function data to 36 months post‐transplant were analyzed from the prospective, observational Mycophenolic acid Observational REnal transplant (MORE) registry in which de novo kidney transplant patients were managed according to local practice. Tacrolimus trough (C0) concentration at month 12 was stratified as low (<6 ng/mL), moderate (6–8 ng/mL), or high (>8 ng/mL) in 724 patients. Estimated glomerular filtration rate (eGFR) was stratified as low (<60 mL/min/1.73 m2) or high (≥60 mL/min/1.73 m2). High tacrolimus C0 (>8 ng/mL) was observed in 47.7%, 34.1%, 26.8%, and 26.7% of patients at baseline and months 12, 24, and 36, respectively. Biopsy‐proven acute rejection was similar to month 36 regardless of tacrolimus C0 category at month 12. Tacrolimus C0 >8 ng/mL vs. <6 ng/mL at month 12 was predictive of low eGFR at month 24 (p = 0.023) with a nonsignificant trend at month 36 (p = 0.085). Infections (p < 0.013) and BK virus infection (p < 0.001) were most frequent in the low tacrolimus C0 cohort. Neutropenia was most frequent in the high tacrolimus C0 category (p = 0.010). In conclusion, over a quarter of patients were exposed to high tacrolimus C0 to 36 months post‐transplant. Tacrolimus exposure did not affect rejection risk, but tacrolimus C0 >8 ng/mL at month 12 was predictive of subsequent low eGFR compared to C0 <6 ng/mL. 相似文献
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Dihydronaphthofurans (DHNs) are an important class of arene ring-fused furans which are widely found in many natural and non-natural products and drug candidates with relevant biological and pharmacological activities. Furthermore, vinylidene-naphthofurans exhibit photochromic properties when exposed to UV or sun light at room temperature. For these reasons, a vast array of synthetic procedures for the preparation of dihydronaphthofurans including annulation of naphthols with various reagents, cycloaddition reactions ([3 + 2], [4 + 1] and Diels–Alder), intramolecular transannulation, Friedel–Crafts, Wittig, Claisen rearrangement, neophyl rearrangement and other reactions under various conditions have been developed over the past decades. This review aims to describe the different strategies developed so far for the synthesis of dihydronaphthofurans and their applications. After a brief introduction to the types of dihydronaphthofurans and their biological activities, the different synthetic approaches such as chemical, photochemical, and electrochemical, methods are described and organized on the basis of the catalysts and the other reagents employed in the syntheses. The subsequent section focuses on biological and pharmacological applications and photochromic properties of the target compounds.Dihydronaphthofurans (DHNs) are an important class of arene ring-fused furans which are widely found in many natural and non-natural products and drug candidates with relevant biological and pharmacological activities. 相似文献
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The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques 总被引:9,自引:5,他引:9
Philpott NJ; Turner AJ; Scopes J; Westby M; Marsh JC; Gordon-Smith EC; Dalgleish AG; Gibson FM 《Blood》1996,87(6):2244-2251
The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states. 相似文献
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Laura F. Newell Jennifer Dunlap Ken Gatter Grover C. Bagby Richard D. Press Rachel J. Cook Luke Fletcher Jessica T. Leonard Kelli M. Leong Joseph S. Bubalo Ali Olyaei Thomas G. Deloughery Richard T. Maziarz Erin Maynard Susan L. Orloff C. Kristian Enestvedt 《American journal of transplantation》2021,21(12):3894-3906
Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.