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991.
Abhishek A. Mangaonkar Fahim Thawer James Son Germame Ajebo Hongyan Xu Nadine J. Barrett Leigh G. Wells Latanya Bowman Betsy Clair Niren Patel Pritam Bora Grace Jung Elizabeta Nemeth Abdullah Kutlar 《British journal of haematology》2020,189(6):1204-1209
Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non-IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = −0·2, P = 0·4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0·4, P = 0·08) and non-IO state (Spearman ρ = −0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD. 相似文献
992.
Hassan Awada Reda Z. Mahfouz Ashwin Kishtagari Teodora Kuzmanovic Jibran Durrani Cassandra M. Kerr Bhumika J. Patel Valeria Visconte Tomas Radivoyevitch Alan Lichtin Hetty E. Carraway Jaroslaw P. Maciejewski Yogen Saunthararajah 《British journal of haematology》2020,188(6):924-929
The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1–2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly. 相似文献
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995.
Snehalata C. Gupte Pratima N. Patel 《Indian journal of hematology & blood transfusion》2014,30(3):175-179
The study presents the data analysis (1) To find out the trend of blood component use during the period 2003–2010 and to determine impact of component awareness programs on reduction in whole blood (WB) and single unit transfusions. (2) To determine Hb trigger. The details about blood units issued were entered in the integrated blood bank management software as well as in Microsoft Excel. The data of 4,838 cases of pregnancy anemia; 2,244 receiving blood for obstetric (Ob) hemorrhage including 270 cases of disseminated intravascular coagulation; 1,413 women having Gynecological (Gy) bleeding; 911 Ob, 2,032 Gy and 740 surgeries for Gy malignancy were analyzed. During the years 2003–2010 there was gradual increase in component utilization for pregnancy anemia, Ob/Gy surgeries and Ob/Gy bleeding and significant reduction in WB transfusions due to component awareness programs. But single unit transfusions showed comparatively lower trend of reduction. The mean Hb was 6.4 g/dL for pregnancy anemia, 8.1 g/dL for surgeries and 7.3 g/dL for Ob/Gy bleeding. 相似文献
996.
Manisha M. Brahmbhatt Pina J. Trivedi Dharmesh M. Patel Shilin N. Shukla Prabhudas S. Patel 《Indian journal of hematology & blood transfusion》2014,30(4):241-246
The BCR/ABL gene rearrangement is cytogenetically visualized in most chronic myeloid leukemia (CML) cases. About 5–10 % of CML patients lack its cytogenetic evidence, however, shows BCR/ABL fusion by molecular methods. We describe two CML patients with Philadelphia (Ph) negative (−ve) and BCR/ABL positive by fluorescence in situ hybridization (FISH). Both the cases were in chronic phase at diagnosis. Conventional cytogenetics and different FISH assays were adopted using BCR/ABL probes. Home-brew FISH assay using bacterial artificial clone (BAC) for BAC-CTA/bk 299D3 for chromosomal region 22q13.31-q13.32 was performed in case 1. Both the patients were Ph-ve. In first case, dual color dual fusion (DCDF)-FISH studies revealed 1 Red (R) 2 Green (G) 1 Fusion (F) signal pattern in 80 % of cells indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph and 2G2F signal pattern in 20 % of cells indicating two BCR/ABL fusions on both chromosomes 9q34 on presentation. In second case, FISH studies revealed the 1R1G1F signal pattern indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph in 100 % of cells at presentation. During follow-up, both the patients exhibited 2G2F signal pattern indicating two BCR/ABL fusions on both chromosomes 9q34, which indicated a clonal evolution in 100 % cells. Both the patients did not achieve therapeutic response. Relocation of BCR/ABL fusion sequence on sites other than 22q11 represents a rare type of variant Ph, the present study highlights the hot spots involved in CML pathogenesis and signifies their implications in Ph−ve BCR/ABL positive CML. This study demonstrated the genetic heterogeneity of this subgroup of CML and strongly emphasized the role of metaphase FISH, especially in Ph−ve CML cases, as it detects variations of the classical t(9;22). 相似文献
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998.
Shalender Bhasin MB BS Thomas G. Travison PhD Todd M. Manini PhD Sheena Patel MS Karol M. Pencina PhD Roger A. Fielding PhD Jay M. Magaziner PhD Anne B. Newman MD MPH Douglas P. Kiel MD Cyrus Cooper DM FMedSci Jack M. Guralnik MD PhD Jane A. Cauley Dr.PH Hidenori Arai MD PhD Brian C. Clark PhD Francesco Landi MD PhD Laura A. Schaap PhD Suzette L. Pereira PhD Daniel Rooks PhD Jean Woo MD PhD Linda J. Woodhouse PhD Ellen Binder MD Todd Brown MD Michelle Shardell PhD Quian-Li Xue PhD Ralph B. DʼAgostino Sr PhD Denise Orwig PhD Greg Gorsicki PhD Rosaly Correa-De-Araujo MD PhD Peggy M. Cawthon PhD 《Journal of the American Geriatrics Society》2020,68(7):1410-1418
999.
High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (Ts) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in product temperature (Tp) above the collapse temperature (Tc) and a significant reduction (of at least 40%) in process time compared to the control cycle (wherein Tp < Tc). For the amorphous-only formulation at a protein concentration of ≤25 mg/mL, single-step drying resulted in product shrinkage and partial collapse, whereas a 50 mg/mL concentration showed minor product shrinkage. The presence of a crystallizing bulking agent improved product appearance at ≤25 mg/mL protein concentration for single-step drying. No impact to other product quality attributes was observed for single-step drying. Vial type, fill height, and scale-up considerations (i.e., choked flow, condenser capacity, lyophilizer design and geometry) were the important factors identified for successful implementation of single-step drying. Although single-step drying showed significant reduction in the edge vial effect, the scale-up considerations need to be addressed critically. Finally, the single-step drying approach can indeed make the lyophilization process high throughput compared to traditional freeze-drying process (i.e., 2-step drying). 相似文献
1000.