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101.
Mitchell L. Ramsey Erin Talbert Daniel Ahn Tanios Bekaii-Saab Niharika Badi P. Mark Bloomston Darwin L. Conwell Zobeida Cruz-Monserrate Mary Dillhoff Matthew R. Farren Alice Hinton Somashekar G. Krishna Gregory B. Lesinski Thomas Mace Andrei Manilchuk Anne Noonan Timothy M. Pawlik Priyani V. Rajasekera Phil A. Hart 《Pancreatology》2019,19(1):80-87
Background
Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression.Methods
We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models.Results
On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p?<?0.001 for multiplex and p?=?0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was.Conclusion
Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia. 相似文献102.
Rosenfeld M Gibson RL McNamara S Emerson J Burns JL Castile R Hiatt P McCoy K Wilson CB Inglis A Smith A Martin TR Ramsey BW 《Pediatric pulmonology》2001,32(5):356-366
A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy. 相似文献
103.
104.
Haley Ramsey Qi Zhang Diane E. Brown David P. Steensma Charles P. Lin Mei X. Wu 《Haematologica》2014,99(2):282-291
Expression of the immediate early response gene X-1 (IEX-1, IER3) is diminished significantly in hematopoietic stem cells in a subgroup of patients with early stage myelodysplastic syndromes, but it is not clear whether the deregulation contributes to the disease. The current study demonstrates increased apoptosis and a concomitant decrease in the number of hematopoietic stem cells lacking this early response gene. Null mutation of the gene also impeded platelet differentiation and shortened a lifespan of red blood cells. When bone marrow cells deficient in the gene were transplanted into wild-type mice, the deficient stem cells produced significantly fewer circulating platelets and red blood cells, despite their enhanced repopulation capability. Moreover, after exposure to a non-myeloablative dose of radiation, absence of the gene predisposed to thrombocytopenia, a significant decline in red blood cells, and dysplastic bone marrow morphology, typical characteristics of myelodysplastic syndromes. These findings highlight a previously unappreciated role for this early response gene in multiple differentiation steps within hematopoiesis, including thrombopoiesis, erythropoiesis and in the regulation of hematopoietic stem cell quiescence. The deficient mice offer a novel model for studying the initiation and progression of myelodysplastic syndromes as well as strategies to prevent this disorder. 相似文献
105.
Ramsey N. Majzoub Chia-Ling Chan Kai K. Ewert Bruno F.B. Silva Keng S. Liang Erica L. Jacovetty Bridget Carragher Clinton S. Potter Cyrus R. Safinya 《Biomaterials》2014
Steric stabilization of cationic liposome–DNA (CL–DNA) complexes is required for in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene glycol)) of CL–DNA complexes by addition of PEG2000-lipids yields sterically stabilized nanoparticles but strongly reduces their gene delivery efficacy. PEGylation-induced weakening of the electrostatic binding of CL–DNA nanoparticles to cells (leading to reduced uptake) has been considered as a possible cause, but experimental results have been ambiguous. Using quantitative live-cell imaging in vitro, we have investigated cell attachment and uptake of PEGylated CL–DNA nanoparticles with and without a custom synthesized RGD-peptide grafted to the distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly increased cellular attachment as well as uptake compared to nanoparticles without grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL–DNA NPs increases by about an order of magnitude between NPs with low and high membrane charge density (σM; the average charge per unit area of the membrane; controlled by the molar ratio of cationic to neutral lipid), even though imaging data show that uptake of RGD-tagged particles is only slightly enhanced by high σM. This suggests that endosomal escape and, as a result, transfection efficiency of RGD-tagged NPs is facilitated by high σM. We present a model describing the interactions between PEGylated CL–DNA nanoparticles and the anionic cell membrane which shows how the PEG grafting density and membrane charge density affect adhesion of nanoparticles to the cell surface. 相似文献
106.
107.
Dan Cojocari Brianna N Smith Julie J. Purkal Maria P. Arrate Jason D. Huska Yu Xiao Agnieszka Gorska Leah J. Hogdal Haley E. Ramsey Erwin R. Boghaert Darren C. Phillips Michael R. Savona 《Haematologica》2022,107(4):825
Dysregulation of apoptotic machinery is one mechanism by which acute myeloid leukemia (AML) acquires a clonal survival advantage. B-cell lymphoma protein-2 (BCL2) overexpression is a common feature in hematologic malignancies. The selective BCL2 inhibitor, venetoclax (VEN) is used in combination with azacitidine (AZA), a DNAmethyltransferase inhibitor (DNMTi), to treat patients with AML. Despite promising response rates to VEN/AZA, resistance to the agent is common. One identified mechanism of resistance is the upregulation of myeloid cell leukemia-1 protein (MCL1). Pevonedistat (PEV), a novel agent that inhibits NEDD8-activating enzyme, and AZA both upregulate NOXA (PMAIP1), a BCL2 family protein that competes with effector molecules at the BH3 binding site of MCL1. We demonstrate that PEV/AZA combination induces NOXA to a greater degree than either PEV or AZA alone, which enhances VEN-mediated apoptosis. Herein, using AML cell lines and primary AML patient samples ex vivo, including in cells with genetic alterations linked to treatment resistance, we demonstrate robust activity of the PEV/VEN/AZA triplet. These findings were corroborated in preclinical systemic engrafted models of AML. Collectively, these results provide rational for combining PEV/VEN/AZA as a novel therapeutic approach in overcoming AML resistance in current therapies. 相似文献
108.
109.
Arianne C Lim Kitty WM Bloemenkamp Kees Boer Johannes J Duvekot Jan Jaap HM Erwich Tom HM Hasaart Pieter Hummel Ben WJ Mol Jos PM Offermans Charlotte M van Oirschot Job G Santema Hubertina CJ Scheepers Willem A Schöls Frank PHA Vandenbussche Maurice GAJ Wouters Hein W Bruinse 《BMC pregnancy and childbirth》2007,7(1):1-6
Background
Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.Methods
552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.Results
The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.Conclusion
Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy. 相似文献110.
Bradley A. Fritz Brett Ramsey Dick Taylor John Paul Shoup Jennifer M. Schmidt Megan Guinn Thomas M. Maddox 《Journal of general internal medicine》2022,37(4):838
BackgroundCOVID-positive outpatients may benefit from remote monitoring, but such a program often relies on smartphone apps. This may introduce racial and socio-economic barriers to participation. Offering multiple methods for participation may address these barriers.Objectives(1) To examine associations of race and neighborhood disadvantage with patient retention in a monitoring program offering two participation methods. (2) To measure the association of the program with emergency department visits and hospital admissions.DesignRetrospective propensity-matched cohort study.ParticipantsCOVID-positive outpatients at a single university-affiliated healthcare system and propensity-matched controls.InterventionsA home monitoring program providing daily symptom tracking via patient portal app or telephone calls.Main MeasuresAmong program enrollees, retention (until 14 days, symptom resolution, or hospital admission) by race and neighborhood disadvantage, with stratification by program arm. In enrollees versus matched controls, emergency department utilization and hospital admission within 30 days.Key ResultsThere were 7592 enrolled patients and 9710 matched controls. Black enrollees chose the telephone arm more frequently than White enrollees (68% versus 44%, p = 0.009), as did those from more versus less disadvantaged neighborhoods (59% versus 43%, p = 0.02). Retention was similar in Black enrollees and White enrollees (63% versus 62%, p = 0.76) and in more versus less disadvantaged neighborhoods (63% versus 62%, p = 0.44). When stratified by program arm, Black enrollees had lower retention than White enrollees in the app arm (49% versus 55%, p = 0.01), but not in the telephone arm (69% versus 71%, p = 0.12). Compared to controls, enrollees more frequently visited the emergency department (HR 1.71 [95% CI 1.56–1.87]) and were admitted to the hospital (HR 1.16 [95% CI 1.02–1.31]).ConclusionsIn a COVID-19 remote patient monitoring program, Black enrollees preferentially selected, and had higher retention in, telephone- over app-based monitoring. As a result, overall retention was similar between races. Remote monitoring programs with multiple modes may reduce barriers to participation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07207-4.KEY WORDS: ambulatory monitoring, COVID-19, race factors, facilities and services utilization 相似文献