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1.
Blood Adv ; 3(21): 3261-3265, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31698457

RESUMO

Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds. A-PACs, isolated from a commercially available cranberry extract, were evaluated for their effects on leukemia cell lines, primary AML samples, and normal CD34+ cord blood specimens. Our results indicated potent and specific antileukemia activity in vitro. In addition, the antileukemia activity of A-PACs extended to malignant progenitor and stem cell populations, sparing their normal counterparts. The antileukemia effects of A-PACs were also observed in vivo using patient derived xenografts. Surprisingly, we found that the mechanism of cell death was driven by activation of NF-κB. Overall, our data suggest that A-PACs could be used to improve treatments for AML by targeting leukemia stem cells through a potentially novel pathway.

2.
Leukemia ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492897

RESUMO

Bone marrow mesenchymal stromal cells (MSCs) constitute one of the important components of the hematopoietic microenvironmental niche. In vivo studies have shown that depletion of marrow MSCs resulted in reduction of hematopoietic stem cell content, and there is in vitro evidence that marrow MSCs are able to support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. How MSCs from leukemia marrow differ from normal counterparts and how they are influenced by the presence of leukemia stem and progenitor cells are still incompletely understood. In this work, we compared normal donor (ND) and acute myelogenous leukemia (AML) derived MSCs and found that AML-MSCs had increased adipogenic potential with improved ability to support survival of leukemia progenitor cells. To identify underlying changes, RNA-Seq analysis was performed. Gene ontology and pathway analysis revealed adipogenesis to be among the set of altered biological pathways dysregulated in AML-MSCs as compared with ND-MSCs. Expression of both SOX9 and EGR2 was decreased in AML-MSCs as compared with ND-MSCs. Increasing expression of SOX9 decreased adipogenic potential of AML-MSCs and decreased their ability to support AML progenitor cells. These findings suggest that AML-MSCs possess adipogenic potential which may enhance support of leukemia progenitor cells.

3.
J Am Osteopath Assoc ; 119(9): 578-587, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31449304

RESUMO

Background: Despite a diverse range of curricular advancements to address the difficult transition from classroom learning to clinical training during medical education, hurdles persist. A 4-week course was designed at the Philadelphia College of Osteopathic Medicine (PCOM) to make this transition easier. Objectives: To determine whether PCOM students' comfort and preparedness increased after taking a 4-week clinical transition course before third-year clinical clerkships, and to determine whether faculty perceptions of student preparedness and comfort were improved after participation in the course compared with previous third-year students. Methods: Second-year osteopathic medical students at PCOM participated in a 4-week course, Introduction to Clinical Clerkship (I2C). The course included 16 small-group exercises, which all took place before students began their third-year clerkship rotations. The exercises in the course extended beyond the skills learned during their classroom years. Students were given a pre- and postcourse survey to evaluate their comfort level with 58 different aspects of clinical practice. Participating faculty were surveyed to evaluate their perception of student preparedness and comfort compared with previous third-year students who had not undergone the exercise. Results: After completing the I2C course, third-year osteopathic medical students (n=232) reported increased comfort with 57 of the 58 learning objectives and each of the 5 coded clinical competency areas (patient assessment, effective communication, hospital logistics, procedural skills, and core knowledge) (P<.01). Preceptors reported that students who completed the I2C course were more prepared (54.5%) and more comfortable (63.4%) with clinical duties, as compared with their recollections of previous third-year osteopathic medical students. Conclusion: Within the 5 competencies, students on average felt more comfortable and were perceived by faculty as better prepared than previous students who had not taken the I2C course. The establishment of a preclinical transition exercise appears to help bridge the gap between the preclinical and clinical years. This learning model allows medical students to feel both more comfortable and better prepared throughout the transition from classroom learning to clinical rotations.

4.
J Am Osteopath Assoc ; 119(9): 612-619, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31449307

RESUMO

Interprofessional education (IPE) is necessary to ensure that future health care professionals are prepared to provide holistic, patient-centered prevention programs, assessments, diagnoses, treatment plans, and chronic illness management in a collaborative manner. Accrediting bodies such as the Commission on Osteopathic College Accreditation and the American Psychological Association newly require programs to implement instruction and evaluate IPE core competency development in each year of their programs. The IPE core team at the Philadelphia College of Osteopathic Medicine has designed, implemented, and tested an IPE core course over the past 2 years that includes students in osteopathic medicine, clinical psychology, mental health counseling, and physician assistant programs. Throughout this process, the IPE core team has identified strengths, weaknesses, opportunities, and challenges. Cultural considerations, institutional resources, pedagogy for large interdisciplinary groups at different stages of training, and technology and assessment tools for student and course evaluation are all critical considerations.

5.
J Wildl Dis ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31403899

RESUMO

We determined the temporal aspects of detecting bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) in postmortem bone marrow samples of white-tailed deer (Odocoileus virginianus) using molecular and in vitro cell culture techniques. Bone marrow samples from carcasses were collected and assayed on the day of death and at intervals up to 16 wk after death. We recovered BTV and EHDV from fresh bone marrow collected at day 0 by isolation in Vero and BHK-21 cell cultures. However, attempts to replicate the viruses from aged bone marrow in Vero and BHK-21 cell cultures failed. The real-time quantitative reverse transcriptase PCR (qRT-PCR) results confirmed that EHDV and BTV can be detected in aged bone marrow for up to 12 and 16 wk, respectively, after death. The RNA of BTV and EHDV could be detected by qRT-PCR in white-tailed deer bone marrow for extended periods of time after postmortem. This technique will provide a useful tool for retrospective determination of BTV or EHDV infection of white-tailed deer at the time of death.

6.
Kidney Blood Press Res ; 44(4): 690-703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31416075

RESUMO

BACKGROUND AND OBJECTIVES: Patients with chronic kidney disease (CKD) exhibit a highly increased risk of cardiovascular (CV) morbidity and mortality. Subtle changes in left ventricular function can be detected by two-dimensional (2D) speckle tracking echocardiography (STE). This study investigated whether myocardial dysfunction detected by 2D STE may aid in CV and all-cause mortality risk assessment in patients with CKD stages 3 and 4. METHOD: A study group of 285 patients (CKD 3: 193 patients; CKD 4: 92 patients) and a healthy control group (34 participants) were included in the retrospective study. 2D STE values as well as early and late diastolic strain rates were measured in ventricular longitudinal, circumferential and radial directions. Patients' CV and all-cause outcome was determined. RESULTS: In the CKD group all measured longitudinal STE values and radial strain were significantly reduced compared to the control group. Cox proportional hazards regression revealed global longitudinal strain to predict CV and all-cause mortality (hazard ratio [HR] 1.15, 95% CI 1.06-1.25; p = 0.0008 and HR 1.09, 95% CI 1.04-1.14; p = 0.0003). After adjustment for sex, age, diabetes, estimated glomerular filtration rate, and preexisting CV disease, this association was maintained for CV mortality and all-cause mortality (HR 1.16, 95% CI 1.06-1.27; p = 0.0019 and HR 1.08, 95% CI 1.03-1.14; p = 0.0026, respectively). CONCLUSIONS: The present study shows that 2D STE detects reduced left ventricular myocardial function and allows the prediction of CV and all-cause mortality in patients at CKD stages 3 and 4.

7.
J Gen Intern Med ; 34(9): 1841-1847, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313110

RESUMO

BACKGROUND: Development of electronic health record (EHR) prediction models to improve palliative care delivery is on the rise, yet the clinical impact of such models has not been evaluated. OBJECTIVE: To assess the clinical impact of triggering palliative care using an EHR prediction model. DESIGN: Pilot prospective before-after study on the general medical wards at an urban academic medical center. PARTICIPANTS: Adults with a predicted probability of 6-month mortality of ≥ 0.3. INTERVENTION: Triggered (with opt-out) palliative care consult on hospital day 2. MAIN MEASURES: Frequencies of consults, advance care planning (ACP) documentation, home palliative care and hospice referrals, code status changes, and pre-consult length of stay (LOS). KEY RESULTS: The control and intervention periods included 8 weeks each and 138 admissions and 134 admissions, respectively. Characteristics between the groups were similar, with a mean (standard deviation) risk of 6-month mortality of 0.5 (0.2). Seventy-seven (57%) triggered consults were accepted by the primary team and 8 consults were requested per usual care during the intervention period. Compared to historical controls, consultation increased by 74% (22 [16%] vs 85 [63%], P < .001), median (interquartile range) pre-consult LOS decreased by 1.4 days (2.6 [1.1, 6.2] vs 1.2 [0.8, 2.7], P = .02), ACP documentation increased by 38% (23 [17%] vs 37 [28%], P = .03), and home palliative care referrals increased by 61% (9 [7%] vs 23 [17%], P = .01). There were no differences between the control and intervention groups in hospice referrals (14 [10] vs 22 [16], P = .13), code status changes (42 [30] vs 39 [29]; P = .81), or consult requests for lower risk (< 0.3) patients (48/1004 [5] vs 33/798 [4]; P = .48). CONCLUSIONS: Targeting hospital-based palliative care using an EHR mortality prediction model is a clinically promising approach to improve the quality of care among seriously ill medical patients. More evidence is needed to determine the generalizability of this approach and its impact on patient- and caregiver-reported outcomes.

8.
Dtsch Arztebl Int ; 116(20): 347-354, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31288916

RESUMO

BACKGROUND: Foot drop can be caused by a variety of diseases and injuries. Although it is a common condition, its overall incidence has not been reported to date. Foot drop markedly restricts the everyday activities of persons suffering from it. There is, therefore, a need for an optimized strategy for its diagnosis and treatment that would be standardized across the medical specialties encountering patients with this problem. METHODS: This article consists of a review on the basis of pertinent publications re- trieved by a search in the Pubmed/MEDLINE and Cochrane databases, as well as a description of the authors' proposed strategy for the diagnosis and treatment of foot drop. RESULTS: Foot drop can be due to a disturbance at any central or peripheral location along the motor neural pathway that terminates in the dorsiflexor muscles of the foot, or at multiple locations in series. Optimal localization of the lesion(s) is a pre- requisite for appropriate treatment and a successful outcome. The most common causes are L5 radiculopathy and peroneal nerve injury. An operation by a neuro- surgeon or spinal surgeon is a reasonable option whenever there is a realistic chance that the nerve will recover. In our opinion, any patient with a subjectively disturbing foot drop and a clinically suspected compressive neuropathy of the peroneal nerve should be informed about the option of surgical decompression of the nerve at the fibular head, which can be performed with little risk. In case of a permanent foot drop, some patients can benefit from muscle-transfer surgery. For spastic foot drop, the option of botulinum toxin injections should be evaluated. CONCLUSION: The care of patients with foot drop could be optimized by interdisciplin- ary foot-drop clinics involving all of the relevant specialists. The goals of treatment should always be improved mobility in everyday life and the prevention of falls, pain, and abnormal postures.

9.
J Insect Sci ; 19(4)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268545

RESUMO

The 2018 student debates of the Entomological Society of America were held at the Joint Annual Meeting for the Entomological Societies of America, Canada, and British Columbia in Vancouver, BC. Three unbiased introductory speakers and six debate teams discussed and debated topics under the theme 'Entomology in the 21st Century: Tackling Insect Invasions, Promoting Advancements in Technology, and Using Effective Science Communication'. This year's debate topics included: 1) What is the most harmful invasive insect species in the world? 2) How can scientists diffuse the stigma or scare factor surrounding issues that become controversial such as genetically modified organisms, agricultural biotechnological developments, or pesticide chemicals? 3) What new/emerging technologies have the potential to revolutionize entomology (other than Clustered Regularly Interspaced Short Palindromic Repeats)? Introductory speakers and debate teams spent approximately 9 mo preparing their statements and arguments and had the opportunity to share this at the Joint Annual Meeting with an engaged audience.


Assuntos
Entomologia/tendências , Insetos , Animais , Biotecnologia , Espécies Introduzidas
10.
Dev Psychol ; 55(10): 2231-2248, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31343229

RESUMO

What drives socioeconomic success within a society? This study analyzes how late childhood intelligence, parental socioeconomic background, and gender relate to multiple dimensions of adult socioeconomic success (i.e., education, occupational status, and income). A particular focus is placed on education, which is considered as both an indicator of socioeconomic success and a mediator of the relationships with the other dimensions. Randomly sampled participants (N = 5,292) in a German prospective longitudinal study were assessed for the first time at age 12 years in 1991 and for the last time as adults in 2009-10. Comparison of the effects of childhood intelligence and parental socioeconomic background revealed childhood intelligence to be the more powerful predictor of the 3 dimensions of later adult socioeconomic success. Education was the strongest predictor of both later adult occupational status and later adult income, and mediated most of the effects of childhood intelligence and parental socioeconomic background on later adult occupational status and later adult income. A gender income gap was apparent, with men reporting higher income, even when childhood factors and education were controlled. Education barely mediated any gender differences, but family-related structural factors (i.e., working part time and having children) explained much of the gender gap in income. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

11.
J Pers ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31173368

RESUMO

OBJECTIVE: This study examined associations between the five-factor personality traits and indicators of academic achievement (grades and test scores). A particular aim was to investigate whether personality-achievement associations differ between primary and secondary educational contexts and whether these differences vary between differential learning environments, that is academic versus nonacademic secondary schools. METHOD: We used two representative random samples from Germany: N = 3,658 6th graders in their last year of primary school and N = 2,129 9th graders attending different secondary school tracks (n = 566 academic track students; n = 1,563 nonacademic track students). RESULTS: First, our results confirmed positive associations between Conscientiousness, Openness, Extraversion, and Agreeableness and academic achievement as well as negative associations between academic achievement and Neuroticism. Second, associations with Conscientiousness were more pronounced for school grades than for test scores. Third, associations were higher for 6th than for 9th graders in the overall sample for all personality traits with the exception of Openness. Fourth, personality-achievement associations differed between academic and nonacademic track students. CONCLUSION: In sum, our results suggest the need for an educational stage-specific perspective and contextually sensitive approach when examining personality-achievement associations.

12.
Blood Rev ; 36: 57-69, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036385

RESUMO

The myelodysplastic syndromes (MDS) represent neoplasms derived from the expansion of mutated clonal hematopoietic cells which often demonstrate aberrant differentiation potential with resultant cytopenias and a propensity to evolve into acute myelogenous leukemia. While multiple mutations have been identified which may serve as drivers of the MDS clone, there is accumulating evidence that MDS clones and subclones are subject to modulation by the marrow microenvironment and its inflammatory milieu. There is also a strong link between autoimmune disorders and MDS. In this review, we examine the role of inflammatory cytokines, toll like receptors, pyroptosis, stromal cells, and cellular inflammatory mediators in MDS initiation, propagation, and progression. These contributions in a background of mutational, epigenetic, and aging changes in the marrow are also reviewed. Such inflammatory mediators may be subject to therapeutic agents which will enhance suppression of the MDS clone with potential to improve therapeutic outcomes in this disease which is usually incurable in aged patients not eligible for stem cell transplantation.

13.
J Integr Plant Biol ; 61(5): 639-650, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30941858

RESUMO

Brassica napus L. (canola) is one of the world's most economically important oilseeds. Despite our growing knowledge of Brassica genetics, we still know little about the genes and gene regulatory networks underlying early seed development. In this work, we use laser microdissection coupled with RNA sequencing to profile gene activity of both the maternal and filial subregions of the globular seed. We find subregions of the chalazal end including the chalazal endosperm, chalazal proliferating tissue, and chalazal seed coat, have unique transcriptome profiles associated with hormone biosynthesis and polysaccharide metabolism. We confirm that the chalazal seed coat is uniquely enriched for sucrose biosynthesis and transport, and that the chalazal endosperm may function as an important regulator of the maternal region through brassinosteroid synthesis. The chalazal proliferating tissue, a poorly understood subregion, was specifically enriched in transcripts associated with megasporogenesis and trehalose biosynthesis, suggesting this ephemeral structure plays an important role in both sporophytic development and carbon nutrient balance, respectively. Finally, compartmentalization of transcription factors and their regulatory circuits has uncovered previously unknown roles for the chalazal pole in early seed development.


Assuntos
Brassica napus/genética , Sementes/genética , Transcriptoma/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética
14.
Plant Physiol Biochem ; 139: 350-365, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952087

RESUMO

Over-expression of the corn phytoglobin ZmPgb1.2 increases tolerance to waterlogging, while suppression of ZmPgb1.2 compromises plant growth. To unravel compartment-specific transcriptional changes evoked by ZmPgb1.2 during hypoxia, laser micro-dissected sub-regions from waterlogged roots of WT and ZmPgb1.2 overexpressing [ZmPgb1.2(S)] plants were probed for global transcriptional analysis using next generation RNA sequencing. These sub-regions included compartments within the meristematic, elongation, and maturation zone. Of the 149 genes differentially expressed by the up-regulation of ZmPgb1.2, 78 occurred within the meristematic region and included genes involved in jasmonic acid synthesis and response, ascorbic acid metabolism, and ethylene signalling. The ZmPgb1.2 regulation of these genes, discussed in the context of known functions of Pgbs, was further validated by monitoring their expression in meristematic cells of waterlogged roots suppressing ZmPgb1.2. Of the 27 genes differentially expressed by the over-expression of ZmPgb1.2 in the elongation zone, pyruvate kinase and alcohol dehydrogenase showed an expression pattern correlated to the level of ZmPgb1.2 in the tissue. The transcriptional induction of these two enzymes in hypoxic domains of the elongation zone over-expressing ZmPgb1.2 suggests the activation of the fermentation pathway which might be required to sustain metabolic flux and production of ATP in support of cell elongation.


Assuntos
Hemoglobinas/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas , Meristema/metabolismo
15.
JCI Insight ; 52019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30998506

RESUMO

The bone marrow microenvironment (BMME) contributes to the regulation of hematopoietic stem cell (HSC) function, though its role in age-associated lineage skewing is poorly understood. Here we show that dysfunction of aged marrow macrophages (Mφs) directs HSC platelet-bias. Mφs from the marrow of aged mice and humans exhibited an activated phenotype, with increased expression of inflammatory signals. Aged marrow Mφs also displayed decreased phagocytic function. Senescent neutrophils, typically cleared by marrow Mφs, were markedly increased in aged mice, consistent with functional defects in Mφ phagocytosis and efferocytosis. In aged mice, Interleukin 1B (IL1B) was elevated in the bone marrow and caspase 1 activity, which can process pro-IL1B, was increased in marrow Mφs and neutrophils. Mechanistically, IL1B signaling was necessary and sufficient to induce a platelet bias in HSCs. In young mice, depletion of phagocytic cell populations or loss of the efferocytic receptor Axl expanded platelet-biased HSCs. Our data support a model wherein increased inflammatory signals and decreased phagocytic function of aged marrow Mφs induce the acquisition of platelet bias in aged HSCs. This work highlights the instructive role of Mφs and IL1B in the age-associated lineage-skewing of HSCs, and reveals the therapeutic potential of their manipulation as antigeronic targets.

16.
ACS Appl Mater Interfaces ; 11(18): 16991-17000, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30932470

RESUMO

The combination of conductivity, optical transparency, and wide anodic potential window has driven significant interest in indium tin oxide (ITO) as an electrode material for electrochemical measurements. More recently, ITO has been applied to the detection of trace metals using cathodic stripping voltammetry (CSV), specifically manganese (Mn). However, the optimization of ITO fabrication for a voltammetric method such as CSV is yet to be reported, nor have the microstructural properties of ITO been investigated for CSV. Furthermore, CSV does not require optical transparency, thereby allowing nontransparent substrates to be used for deposition. This enables microfabrication procedures to be expanded and simplified compared to glass or quartz. Combining this with the profound importance of sensitive, selective detection of toxic metal ions in environmentally and biologically relevant samples makes ITO especially attractive. In this work, we report a thorough investigation of ITO deposition and processing on silicon (Si) substrates for CSV analysis using Mn as the model analyte. Several ITO process parameters were examined such as heated deposition and post-process annealing. Each ITO film was characterized using a variety of surface, bulk (X-ray diffraction), and electrochemical measurements. Although each ITO film type showed electrochemical activity, the heated and annealed (HA) ITO fabrication process yielded superior results for Mn CSV; a limit of detection (LOD) of 0.1 ppb (1.8 nM) was obtained. This work exemplifies new applications of ITO as an electrode material while providing a baseline for trace detection of toxic metals and other contaminants amenable to detection by CSV.

17.
Mol Plant Microbe Interact ; 32(8): 1001-1012, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30938576

RESUMO

Our study investigated disease resistance in the Brassica napus-Leptosphaeria maculans pathosystem using a combination of laser microdissection, dual RNA sequencing, and physiological validations of large-scale gene sets. The use of laser microdissection improved pathogen detection and identified putative L. maculans effectors and lytic enzymes operative during host colonization. Within 24 h of inoculation, we detected large shifts in gene activity in resistant cotyledons associated with jasmonic acid and calcium signaling pathways that accelerated the plant defense response. Sequencing data were validated through the direct quantification of endogenous jasmonic acid levels. Additionally, resistance against L. maculans was abolished when the calcium chelator EGTA was applied to the inoculation site, providing physiological evidence of the role of calcium in B. napus immunity against L. maculans. We integrated gene expression data with all available information on cis-regulatory elements and transcription factor binding affinities to better understand the gene regulatory networks underpinning plant resistance to hemibiotrophic pathogens. These in silico analyses point to early cellular reprogramming during host immunity that are coordinated by CAMTA, BZIP, and bHLH transcription factors. Together, we provide compelling genetic and physiological evidence into the programming of plant resistance against fungal pathogens.


Assuntos
Ascomicetos , Brassica napus , Resistência à Doença , Interações Hospedeiro-Patógeno , Transcriptoma , Ascomicetos/fisiologia , Brassica napus/genética , Brassica napus/imunologia , Brassica napus/microbiologia , Resistência à Doença/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia
18.
Cell Rep ; 27(1): 238-254.e6, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30943405

RESUMO

The NADPH-dependent oxidase NOX2 is an important effector of immune cell function, and its activity has been linked to oncogenic signaling. Here, we describe a role for NOX2 in leukemia-initiating stem cell populations (LSCs). In a murine model of leukemia, suppression of NOX2 impaired core metabolism, attenuated disease development, and depleted functionally defined LSCs. Transcriptional analysis of purified LSCs revealed that deficiency of NOX2 collapses the self-renewal program and activates inflammatory and myeloid-differentiation-associated programs. Downstream of NOX2, we identified the forkhead transcription factor FOXC1 as a mediator of the phenotype. Notably, suppression of NOX2 or FOXC1 led to marked differentiation of leukemic blasts. In xenotransplantation models of primary human myeloid leukemia, suppression of either NOX2 or FOXC1 significantly attenuated disease development. Collectively, these findings position NOX2 as a critical regulator of malignant hematopoiesis and highlight the clinical potential of inhibiting NOX2 as a means to target LSCs.

19.
Lab Med ; 50(4): 396-400, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30915450

RESUMO

The main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products. The results of an human leukocyte antigen (HLA) class-1 panel reactive antibody assay were 0%, and the results of a platelet-antibody screening assay were positive for HLA class-1 antibodies and glycoprotein (Gp)IIb/IIIa antibodies. Her platelet count reached 42 × 109 per L on day 50, after rituximab on day 22 and daratumumab on day 29. Her clinical scenario was most consistent with the course of PTP.

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