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Search Results: 1 - 10 of 4497 matches for " Craig Freeman "
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Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty
Theresa A Freeman, Javad Parvizi, Craig J Dela Valle, Marla J Steinbeck
Fibrogenesis & Tissue Repair , 2010, DOI: 10.1186/1755-1536-3-17
Abstract: The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species.Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA.Limited range of motion is a disabling complication of total knee arthroplasty (TKA) [1-8]. Idiopathic arthrofibrosis, clinically defined as abnormal tissue scarring within the joint, represents the most severe form of stiffness. Even with surgical intervention or revision arthroplasty, the formation of dense fibrous tissue and tissue contractions can recur, leading to increased severity of the fibrotic condition and eventual disability, with all the negative psychological and societal implications this carries [8]. Unfortunately, there is no clear method by which patients who are at risk of developing arthrof
Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty
Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck
Fibrogenesis & Tissue Repair , 2009, DOI: 10.1186/1755-1536-2-5
Abstract: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG), and protein nitrosylation (nitrotyrosine) were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO). In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3'-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage.Based on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving aggressive fibroblast proliferation and subsequent HO.A number of factors are known to result in complications after total knee arthroplasty (TKA), which include preoperative deformity, neuromuscular disease, patient noncompliance with rehabilitation protocol and technical errors such as component malpositioning [1-4]. A separate portion of the patient population develops arthrofibrosis after TKA, clinically defined as abnormal
Empiric Potassium Supplementation and Increased Survival in Users of Loop Diuretics
Charles E. Leonard, Hanieh Razzaghi, Cristin P. Freeman, Jason A. Roy, Craig W. Newcomb, Sean Hennessy
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102279
Abstract: Background The effectiveness of the clinical strategy of empiric potassium supplementation in reducing the frequency of adverse clinical outcomes in patients receiving loop diuretics is unknown. We sought to examine the association between empiric potassium supplementation and 1) all-cause death and 2) outpatient-originating sudden cardiac death (SD) and ventricular arrhythmia (VA) among new starters of loop diuretics, stratified on initial loop diuretic dose. Methods We conducted a one-to-one propensity score-matched cohort study using 1999–2007 US Medicaid claims from five states. Empiric potassium supplementation was defined as a potassium prescription on the day of or the day after the initial loop diuretic prescription. Death, the primary outcome, was ascertained from the Social Security Administration Death Master File; SD/VA, the secondary outcome, from incident, first-listed emergency department or principal inpatient SD/VA discharge diagnoses (positive predictive value = 85%). Results We identified 654,060 persons who met eligibility criteria and initiated therapy with a loop diuretic, 27% of whom received empiric potassium supplementation (N = 179,436) and 73% of whom did not (N = 474,624). The matched hazard ratio for empiric potassium supplementation was 0.93 (95% confidence interval, 0.89–0.98, p = 0.003) for all-cause death. Stratifying on initial furosemide dose, hazard ratios for empiric potassium supplementation with furosemide <40 and ≥40 milligrams/day were 0.93 (0.86–1.00, p = 0.050) and 0.84 (0.79–0.89, p<0.0001). The matched hazard ratio for empiric potassium supplementation was 1.02 (0.83–1.24, p = 0.879) for SD/VA. Conclusions Empiric potassium supplementation upon initiation of a loop diuretic appears to be associated with improved survival, with a greater apparent benefit seen with higher diuretic dose. If confirmed, these findings support the use of empiric potassium supplementation upon initiation of a loop diuretic.
Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice
Hao Cui, Amos C. Hung, David W. Klaver, Toshiharu Suzuki, Craig Freeman, Christian Narkowicz, Glenn A. Jacobson, David H. Small
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023007
Abstract: Background Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. Methodology/Principal Findings We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. Conclusions/Significance The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
Review of Scott Thumma & Edward R. Gray (Eds.), Gay Religion
Craig This
Journal of Men, Masculinities and Spirituality , 2007,
Abstract: Review of Scott Thumma & Edward R. Gray (Eds.), Gay Religion (Walnut Creek, CA: AltaMira Press, 2004), xvi + 376 pp.
Model-Based Forecasts of North American Forest Growth: A Review  [PDF]
Craig Loehle
American Journal of Climate Change (AJCC) , 2018, DOI: 10.4236/ajcc.2018.74032
Abstract: In the context of climate change, planning for forest management goals becomes more complicated. Possible changes in precipitation, temperature, and CO2 can affect tree growth substantially and potential effects differ by species and region. However, integration of potential forest growth responses to these factors can be achieved using models. Because of the need to understand the range of forest growth forecasts and the strengths and limitations of different modeling approaches, I summarized results from 25 studies of forecasted forest responses over coming decades. Some models used statistical relationships between tree rings and climate to forecast growth responses to future climate, some simulated net photosynthesis of a standard forest canopy, and many used tree or stand growth models at various levels of mechanistic detail. In general, models that included CO2 responses predicted enhanced forest growth by 2100 across most of the commercial timberland areas of the US and Canada. For modest warming, most models showed growth enhancement in most regions. For hotter scenarios, many models and regions showed even more growth enhancement, but some regions such as the Southwest, mountain West, and southwestern Canada were predicted to experience drought stress and increased fire incidence, although projections in these regions were variable. Young stands, angiosperms, and early-successional species were predicted to exhibit the most positive responses. As a result, commercial harvest ages might be accelerated by several years, depending on species. Some simulations for the Midwest and Northeast US predicted a doubling or more of net primary productivity although other studies show a lesser response. Model runs that did not include mechanisms of CO2 fertilization showed positive growth responses in only limited cases and generally showed growth declines. There also was some evidence indicating the potential spread of forest into woodland at shrub or prairie ecotones.
Temporal changes in innate immune signals in a rat model of alcohol withdrawal in emotional and cardiorespiratory homeostatic nuclei
Kate Freeman, Anthony Brureau, Rajanikanth Vadigepalli, Mary M Staehle, Melanie M Brureau, Gregory E Gonye, Jan B Hoek, D Craig Hooper, James S Schwaber
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-97
Abstract: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC samples from adult male rats exposed to a liquid alcohol diet for thirty-five days and in similarly treated animals at four hours and forty-eight hours following alcohol withdrawal. ANOVA was used to identify statistically significant treatment effects. Immunohistochemistry (IHC) and confocal microscopy were performed in a second set of animals during chronic alcohol exposure and subsequent 48-hour withdrawal.Following a chronic alcohol exposure, withdrawal resulted in a statistically significant increase in the expression of mRNAs specific for innate immune markers Ccl2, TNF-α, NOS-2, Tnfrsf1a, and CD74. This response was present in both the CeA and DVC and most prominent at 48 hours. Confocal IHC of samples taken 48 hours into withdrawal demonstrate the presence of TNF-α staining surrounding cells expressing the neural marker NeuN and endothelial cells colabeled with ICAM-1 (CD54) and RECA-1, markers associated with an inflammatory response. Again, findings were consistent in both brain regions.This study demonstrates the rapid induction of Ccl2, TNF-α, NOS-2, Tnfrsf1a and CD74 expression during alcohol withdrawal in both the CeA and DVC. IHC dual labeling showed an increase in TNF-α surrounding neurons and ICAM-1 on vascular endothelial cells 48 hours into withdrawal, confirming the inflammatory response at the protein level. These findings suggest that an abrupt cessation of alcohol intake leads to an acute central nervous system (CNS) inflammatory response in these regions that regulate autonomic and emotional state.
Extended Carbon Line Emission in the Galaxy: Searching for Dark Molecular Gas along the G328 Sightline
Michael G. Burton,Michael C. B. Ashley,Catherine Braiding,Matthew Freeman,Craig Kulesa,Mark G. Wolfire,David J. Hollenbach,Gavin Rowell,James Lau
Physics , 2015, DOI: 10.1088/0004-637X/811/1/13
Abstract: We present spectral data cubes of the [CI] 809GHz, 12CO 115GHz, 13CO 110GHz and HI 1.4GHz line emission from an 1 square degree region along the l = 328{\deg} (G328) sightline in the Galactic Plane. Emission arises principally from gas in three spiral arm crossings along the sight line. The distribution of the emission in the CO and [CI] lines is found to be similar, with the [CI] slightly more extended, and both are enveloped in extensive HI. Spectral line ratios per voxel in the data cubes are found to be similar across the entire extent of the Galaxy. However, towards the edges of the molecular clouds the [CI]/13CO and 12CO/13CO line ratios rise by ~50%, and the [CI]/HI ratio falls by ~10$%. We attribute this to these sightlines passing predominantly through the surfaces of photodissociation regions (PDRs), where the carbon is found mainly as C or C+, while the H2 is mostly molecular, and the proportion of atomic gas also increases. We undertake modelling of the PDR emission from low density molecular clouds excited by average interstellar radiation fields and cosmic-ray ionization to quantify this comparison, finding that depletion of sulfur and reduced PAH abundance is needed to match line fluxes and ratios. Roughly one-third of the molecular gas along the sightline is found to be associated with this surface region, where the carbon is largely not to be found in CO. ~10% of the atomic hydrogen along the sightline is cold gas within PDRs.
Management traits in dairy cattle: dystocia, udder characteristics related to production, and a review of other traits
AE Freeman
Genetics Selection Evolution , 1976, DOI: 10.1186/1297-9686-8-2-288b
Abstract:
Teaching animal breeding in the united states
AE Freeman
Genetics Selection Evolution , 1977, DOI: 10.1186/1297-9686-9-1-132b
Abstract:
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