Sample records for persistent tissue kinetics
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Persistence of Agrobacterium tumefaciens in transformed conifers.
Charity, Julia A; Klimaszewska, Krystyna
2005-01-01
Previous studies have shown that the widely used plant transformation vector Agrobacterium tumefaciens can persist in genetically engineered plants in vitro and in transgenic greenhouse-grown plants, despite the use of counter-selective antibiotics. However, little is known regarding Agrobacterium persistence in tree species. To understand the kinetics of A. tumefaciens decline and persistence in transformation experiments, we assayed for the presence of A. tumefaciens in spruce and pine embryogenic tissue for up to 10 weeks post-transformation. The A. tumefaciens populations declined rapidly in the first five days post-cocultivation but generally declined more slowly in pine, relative to spruce. No bacteria were detected in spruce embryogenic tissue beyond four weeks after cocultivation, however in pine there were -100 colony forming units per g tissue at 10 weeks post-cocultivation. We present evidence that the detection limit for PCR using virD2 primers to detect A. tumefaciens in a background of pine needle DNA was approximately 10(9)-10(10) A. tumefaciens cells per g of tissue. We also assayed for A. tumefaciens in transgenic pine and spruce embryogenic tissue and from needles, branches, stems and roots of transformed plants, up to four years post-inoculation. Occasionally A. tumefaciens was detected in embryogenic tissue up to 12 months post-inoculation. A. tumefaciens was never detected in cultured embryogenic tissue more than twelve months after inoculation, nor in developing somatic embryos or germinating plantlets, nor any of the parts of greenhouse-grown plants. From these data we conclude that if A. tumefaciens persists in transgenic conifers, it does so beneath our ability to detect it.
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Busquets, Núria; Abad, F Xavier; Alba, Anna; Dolz, Roser; Allepuz, Alberto; Rivas, Raquel; Ramis, Antonio; Darji, Ayub; Majó, Natàlia
2010-09-01
Selection of an ideal sample is a vital element in early detection of influenza infection. Rapid identification of infectious individuals or animals is crucial not only for avian influenza virus (AIV) surveillance programmes, but also for treatment and containment strategies. This study used a combination of quantitative real-time RT-PCR with an internal positive control and a cell-titration system to examine the presence of virus in different samples during active experimental AIV infection and its persistence in the infected carcasses. Oropharyngeal/cloacal swabs as well as feather pulp and blood samples were collected from 15-day-old chicks infected with H7N1 highly pathogenic AIV (HPAIV) and the kinetics of virus shedding during active infection were evaluated. Additionally, several samples (muscle, skin, brain, feather pulp and oropharyngeal and cloacal swabs) were examined to assess the persistence of virus in the HPAIV-infected carcasses. Based on the results, feather pulp was found to be the best sample to detect and isolate HPAIV from infected chicks from 24 h after inoculation onwards. Kinetic studies on the persistence of virus in infected carcasses revealed that tissues such as muscle could potentially transmit infectious virus for 3 days post-mortem (p.m.), whilst other tissues such as skin, feather pulp and brain retained their infectivity for as long as 5-6 days p.m. at environmental temperature (22-23 degrees C). These results strongly favour feather as a useful sample for HPAIV diagnosis in infected chickens as well as in carcasses.
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McFadden, Nora; Arias, Armando; Dry, Inga; Bailey, Dalan; Witteveldt, Jeroen; Evans, David J.; Goodfellow, Ian; Simmonds, Peter
2013-01-01
Mechanisms by which certain RNA viruses, such as hepatitis C virus, establish persistent infections and cause chronic disease are of fundamental importance in viral pathogenesis. Mammalian positive-stranded RNA viruses establishing persistence typically possess genome-scale ordered RNA secondary structure (GORS) in their genomes. Murine norovirus (MNV) persists in immunocompetent mice and provides an experimental model to functionally characterize GORS. Substitution mutants were constructed with coding sequences in NS3/4- and NS6/7-coding regions replaced with sequences with identical coding and (di-)nucleotide composition but disrupted RNA secondary structure (F1, F2, F1/F2 mutants). Mutants replicated with similar kinetics to wild-type (WT) MNV3 in RAW264.7 cells and primary macrophages, exhibited similar (highly restricted) induction and susceptibility to interferon-coupled cellular responses and equal replication fitness by serial passaging of co-cultures. In vivo, both WT and F1/F2 mutant viruses persistently infected mice, although F1, F2 and F1/F2 mutant viruses were rapidly eliminated 1–7 days post-inoculation in competition experiments with WT. F1/F2 mutants recovered from tissues at 9 months showed higher synonymous substitution rates than WT and nucleotide substitutions that potentially restored of RNA secondary structure. GORS plays no role in basic replication of MNV but potentially contributes to viral fitness and persistence in vivo. PMID:23630317
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Poe, Stephanie L.; Arora, Meenakshi; Oriss, Timothy B.; Yarlagadda, Manohar; Isse, Kumiko; Khare, Anupriya; Levy, David E.; Lee, Janet S.; Mallampalli, Rama; Ray, Anuradha; Ray, Prabir
2012-01-01
Bacterial pneumonia remains a significant burden worldwide. Although an inflammatory response in the lung is required to fight the causative agent, persistent tissue-resident neutrophils in non-resolving pneumonia can induce collateral tissue damage and precipitate acute lung injury. However, little is known about mechanisms orchestrated in the lung tissue that remove apoptotic neutrophils to restore tissue homeostasis. In mice infected with Klebsiella pneumoniae, a bacterium commonly associated with hospital-acquired pneumonia, we show that interleukin-10 is essential for resolution of lung inflammation and recovery of mice after infection. Although IL-10−/− mice cleared bacteria, they displayed increased morbidity with progressive weight loss and persistent lung inflammation in the later phase after infection. A source of tissue IL-10 was found to be resident CD11b+Gr1intF4/80+ cells resembling myeloid-derived suppressor cells that appeared with a delayed kinetics after infection. These cells efficiently efferocytosed apoptotic neutrophils, which was aided by IL-10. The lung neutrophil burden was attenuated in infected STAT1−/− mice with concomitant increase in the frequency of the MDSC-like cells and lung IL-10 levels. Thus, inhibiting STAT1 in combination with antibiotics may be a novel therapeutic strategy to address inefficient resolution of bacterial pneumonia. PMID:22785228
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Tardieu, Didier; Bailly, Jean-Denis; Skiba, Fabien; Grosjean, François; Guerre, Philippe
2008-09-01
The kinetic of fumonisin B1 (FB1) after a single IV and oral dose, and FB1 persistence in tissue were investigated in turkey poults by HPLC after purification of samples on columns. After IV administration (single-dose: 10mg FB1/kg bw), serum concentration-time curves were best described by a three-compartment open model. Elimination half-life and mean residence time of FB1 were 85 and 52min, respectively. After oral administration (single-dose: 100mg FB1/kg bw) bioavailability was 3.2%; elimination half-life and mean residence time were 214 and 408min, respectively. Clearance of FB1 was 7.6 and 7.5ml/min/kg for IV and oral administration, respectively. Twenty-four hours after the administration of FB1 by the intravenous route, liver and kidney contained the highest levels of FB1 in tissues, level in muscle was low or below the limit of detection (LD, 13microg/kg). The persistence of FB1 in tissue was also studied after administration for 9 weeks of a feed that contained 5, 10 and 20mg FB1+FB2/kg diet. Eight hours after the last intake of 20mg FB1+FB2/kg feed (maximum recommended concentration of fumonisins established by the EU for avian feed), hepatic and renal FB1 concentrations were 119 and 22microg/kg, level in muscles was below the LD.
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Tang, J. Y.
2015-09-03
The Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics are two popular mathematical formulations used in many land biogeochemical models to describe how microbes and plants would respond to changes in substrate abundance. However, the criteria of when to use which of the two are often ambiguous. Here I show that these two kinetics are special approximations to the Equilibrium Chemistry Approximation kinetics, which is the first order approximation to the quadratic kinetics that solves the equation of enzyme-substrate complex exactly for a single enzyme single substrate biogeochemical reaction with the law of mass action and the assumption of quasi-steady-state formore » the enzyme-substrate complex and that the product genesis from enzyme-substrate complex is much slower than the equilibration between enzyme-substrate complexes, substrates and enzymes. In particular, I showed that the derivation of the Michaelis–Menten kinetics does not consider the mass balance constraint of the substrate, and the reverse Michaelis–Menten kinetics does not consider the mass balance constraint of the enzyme, whereas both of these constraints are taken into account in the Equilibrium Chemistry Approximation kinetics. By benchmarking against predictions from the quadratic kinetics for a wide range of substrate and enzyme concentrations, the Michaelis–Menten kinetics was found to persistently under-predict the normalized sensitivity ∂ ln v / ∂ ln k 2 + of the reaction velocity v with respect to the maximum product genesis rate k 2 +, persistently over-predict the normalized sensitivity ∂ ln v / ∂ ln k 1 + of v with respect to the intrinsic substrate affinity k 1 +, persistently over-predict the normalized sensitivity ∂ ln v / ∂ ln [ E ] T of v with respect the total enzyme concentration [ E ] T and persistently under-predict the normalized sensitivity ∂ ln v / ∂ ln [ S ] T of v with respect to the total substrate concentration [ S ] T. Meanwhile, the reverse Michaelis–Menten kinetics persistently under-predicts ∂ ln v / ∂ ln k 2 + and ∂ ln v / ∂ ln [ E ] T, and persistently over-predicts ∂ ln v / ∂ ln k 1 + and ∂ ln v / ∂ ln [ S ] T. In contrast, the Equilibrium Chemistry Approximation kinetics always gives consistent predictions of ∂ ln v / ∂ ln k 2 +, ∂ ln v / ∂ ln k 1 +, ∂ ln v / ∂ ln [ E ] T and ∂ ln v / ∂ ln [ S ] T. Since the Equilibrium Chemistry Approximation kinetics includes the advantages from both the Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics and it is applicable for almost the whole range of substrate and enzyme abundances, soil biogeochemical modelers therefore no longer need to choose when to use the Michaelis–Menten kinetics or the reverse Michaelis–Menten kinetics. I expect removing this choice ambiguity will make it easier to formulate more robust and consistent land biogeochemical models.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tang, J. Y.
The Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics are two popular mathematical formulations used in many land biogeochemical models to describe how microbes and plants would respond to changes in substrate abundance. However, the criteria of when to use either of the two are often ambiguous. Here I show that these two kinetics are special approximations to the equilibrium chemistry approximation (ECA) kinetics, which is the first-order approximation to the quadratic kinetics that solves the equation of an enzyme–substrate complex exactly for a single-enzyme and single-substrate biogeochemical reaction with the law of mass action and the assumption of a quasi-steadymore » state for the enzyme–substrate complex and that the product genesis from enzyme–substrate complex is much slower than the equilibration between enzyme–substrate complexes, substrates, and enzymes. In particular, I show that the derivation of the Michaelis–Menten kinetics does not consider the mass balance constraint of the substrate, and the reverse Michaelis–Menten kinetics does not consider the mass balance constraint of the enzyme, whereas both of these constraints are taken into account in deriving the equilibrium chemistry approximation kinetics. By benchmarking against predictions from the quadratic kinetics for a wide range of substrate and enzyme concentrations, the Michaelis–Menten kinetics was found to persistently underpredict the normalized sensitivity ∂ ln v / ∂ ln k 2 + of the reaction velocity v with respect to the maximum product genesis rate k 2 +, persistently overpredict the normalized sensitivity ∂ ln v / ∂ ln k 1 + of v with respect to the intrinsic substrate affinity k 1 +, persistently overpredict the normalized sensitivity ∂ ln v / ∂ ln [ E] T of v with respect the total enzyme concentration [ E] T, and persistently underpredict the normalized sensitivity ∂ ln v / ∂ ln [ S] T of v with respect to the total substrate concentration [ S] T. Meanwhile, the reverse Michaelis–Menten kinetics persistently underpredicts ∂ ln v / ∂ ln k 2 + and ∂ ln v / ∂ ln [ E] T, and persistently overpredicts ∂ ln v / ∂ ln k 1 + and ∂ ln v / ∂ ln [ S] T. In contrast, the equilibrium chemistry approximation kinetics always gives consistent predictions of ∂ ln v / ∂ ln k 2 +, ∂ ln v / ∂ ln k 1 +, ∂ ln v / ∂ ln [ E] T, and ∂ ln v / ∂ ln [ S] T, indicating that ECA-based models will be more calibratable if the modeled processes do obey the law of mass action. Since the equilibrium chemistry approximation kinetics includes advantages from both the Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics and it is applicable for almost the whole range of substrate and enzyme abundances, land biogeochemical modelers therefore no longer need to choose when to use the Michaelis–Menten kinetics or the reverse Michaelis–Menten kinetics. I expect that removing this choice ambiguity will make it easier to formulate more robust and consistent land biogeochemical models.« less
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Tang, J. Y.
2015-12-01
The Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics are two popular mathematical formulations used in many land biogeochemical models to describe how microbes and plants would respond to changes in substrate abundance. However, the criteria of when to use either of the two are often ambiguous. Here I show that these two kinetics are special approximations to the equilibrium chemistry approximation (ECA) kinetics, which is the first-order approximation to the quadratic kinetics that solves the equation of an enzyme–substrate complex exactly for a single-enzyme and single-substrate biogeochemical reaction with the law of mass action and the assumption of a quasi-steadymore » state for the enzyme–substrate complex and that the product genesis from enzyme–substrate complex is much slower than the equilibration between enzyme–substrate complexes, substrates, and enzymes. In particular, I show that the derivation of the Michaelis–Menten kinetics does not consider the mass balance constraint of the substrate, and the reverse Michaelis–Menten kinetics does not consider the mass balance constraint of the enzyme, whereas both of these constraints are taken into account in deriving the equilibrium chemistry approximation kinetics. By benchmarking against predictions from the quadratic kinetics for a wide range of substrate and enzyme concentrations, the Michaelis–Menten kinetics was found to persistently underpredict the normalized sensitivity ∂ ln v / ∂ ln k 2 + of the reaction velocity v with respect to the maximum product genesis rate k 2 +, persistently overpredict the normalized sensitivity ∂ ln v / ∂ ln k 1 + of v with respect to the intrinsic substrate affinity k 1 +, persistently overpredict the normalized sensitivity ∂ ln v / ∂ ln [ E] T of v with respect the total enzyme concentration [ E] T, and persistently underpredict the normalized sensitivity ∂ ln v / ∂ ln [ S] T of v with respect to the total substrate concentration [ S] T. Meanwhile, the reverse Michaelis–Menten kinetics persistently underpredicts ∂ ln v / ∂ ln k 2 + and ∂ ln v / ∂ ln [ E] T, and persistently overpredicts ∂ ln v / ∂ ln k 1 + and ∂ ln v / ∂ ln [ S] T. In contrast, the equilibrium chemistry approximation kinetics always gives consistent predictions of ∂ ln v / ∂ ln k 2 +, ∂ ln v / ∂ ln k 1 +, ∂ ln v / ∂ ln [ E] T, and ∂ ln v / ∂ ln [ S] T, indicating that ECA-based models will be more calibratable if the modeled processes do obey the law of mass action. Since the equilibrium chemistry approximation kinetics includes advantages from both the Michaelis–Menten kinetics and the reverse Michaelis–Menten kinetics and it is applicable for almost the whole range of substrate and enzyme abundances, land biogeochemical modelers therefore no longer need to choose when to use the Michaelis–Menten kinetics or the reverse Michaelis–Menten kinetics. I expect that removing this choice ambiguity will make it easier to formulate more robust and consistent land biogeochemical models.« less
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Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline
2018-06-01
The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Heterogeneity of human adipose blood flow
Levitt, David G
2007-01-01
Background The long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics. Methods The heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al. Results The volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data. Conclusion Human adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation. PMID:17239252
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Dog response to inactivated canine parvovirus and feline panleukopenia virus vaccines.
Pollock, R V; Carmichael, L E
1982-01-01
Inactivated canine parvovirus (CPV) and inactivated feline panleukopenia virus (FPV) vaccines were evaluated in dogs. Maximal serologic response occurred within 1-2 weeks after vaccination. Antibody titers then declined rapidly to low levels that persisted at least 20 weeks. Immunity to CPV, defined as complete resistance to infection, was correlated with serum antibody titer and did not persist longer than 6 weeks after vaccination with inactivated virus. However, protection against generalized infection was demonstrated 20 weeks after vaccination. In unvaccinated dogs, viremia and generalized infection occurred after oronasal challenge with virulent CPV. In contrast, viral replication was restricted to the intestinal tract and gut-associated lymphoid tissue of vaccinated dogs. Canine parvovirus was inactivated by formalin, beta-propiolactone (BPL), and binary ethylenimine (BEI) in serum-free media; inactivation kinetics were determined. Formalin resulted in a greater loss of viral HA than either BEI of BPL, and antigenicity was correspondingly reduced.
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Luu, H M; Hutter, J C
2001-01-01
We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D(4)) after intravenous (IV), inhalation, or implantation exposures. The model used (14)C-D(4) IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D(4) after inhalation to experimental results in both rats and humans. We then used the model to simulate D(4) kinetics after single and/or repeated D(4) exposures in rats and humans. The model predicted bioaccumulation of D(4) in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P(oct/water) = 5.1), D(4) persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D(4) in fatty tissues should play an important role in the risk assessment of D(4) especially in women exposed daily to multiple personal care products and silicone breast implants. PMID:11712992
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Stromal cells in chronic inflammation and tertiary lymphoid organ formation.
Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge
2015-01-01
Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.
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HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy.
Honeycutt, Jenna B; Thayer, William O; Baker, Caroline E; Ribeiro, Ruy M; Lada, Steven M; Cao, Youfang; Cleary, Rachel A; Hudgens, Michael G; Richman, Douglas D; Garcia, J Victor
2017-05-01
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.
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Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua
2017-02-15
Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised patients with persistent infection. However, answers to the questions as to whether TK-negative (TK - ) HSV-1 can establish persistent infection in brains of immunocompromised hosts and whether neurons in vivo are permissive for TK - HSV-1 remain elusive. Using three genetically engineered HSV-1 TK - mutants and two strains of nude mice deficient in T cells, we found that all three HSV-1 TK - mutants can efficiently establish persistent infection in the brain stem and trigeminal ganglion and detected glycoprotein C, a true late viral antigen, in brainstem neurons. Our study provides evidence that TK - HSV-1 can persist in neural tissues and replicate in brain neurons of immunocompromised hosts. Copyright © 2017 American Society for Microbiology.
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Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu
2016-01-01
ABSTRACT Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484–490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. IMPORTANCE Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised patients with persistent infection. However, answers to the questions as to whether TK-negative (TK−) HSV-1 can establish persistent infection in brains of immunocompromised hosts and whether neurons in vivo are permissive for TK− HSV-1 remain elusive. Using three genetically engineered HSV-1 TK− mutants and two strains of nude mice deficient in T cells, we found that all three HSV-1 TK− mutants can efficiently establish persistent infection in the brain stem and trigeminal ganglion and detected glycoprotein C, a true late viral antigen, in brainstem neurons. Our study provides evidence that TK− HSV-1 can persist in neural tissues and replicate in brain neurons of immunocompromised hosts. PMID:27974554
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HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Honeycutt, Jenna B.; Thayer, William O.; Baker, Caroline E.
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA andmore » DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.« less
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HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy
Honeycutt, Jenna B.; Thayer, William O.; Baker, Caroline E.; ...
2017-04-17
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA andmore » DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.« less
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HIV persistence in tissue macrophages of humanized myeloid only mice during antiretroviral therapy
Honeycutt, J. B.; Thayer, W.O.; Baker, C. E.; Ribeiro, R.M.; Lada, S.M.; Cao, Y.; Cleary, R. A.; Hudgens, M. G.; Richman, D.D.; Garcia, J. V.
2017-01-01
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in the host and is never eradicated. One major barrier to eradication is that multiple different cell types are infected that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV disease (1–3); however, their specific role in HIV persistence during long-term suppressive ART has not been established (4–6). Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as determined by a rapid drop in plasma viral load and a dramatic drop in the levels of cell-associated viral RNA and DNA. No virus rebound was observed in the plasma of 67% of the ART treated animals at seven weeks post-ART interruption, and no replication competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a significantly delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence of HIV persistence in tissue macrophages in vivo. PMID:28414330
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Two-photon excited photoconversion of cyanine-based dyes
NASA Astrophysics Data System (ADS)
Kwok, Sheldon J. J.; Choi, Myunghwan; Bhayana, Brijesh; Zhang, Xueli; Ran, Chongzhao; Yun, Seok-Hyun
2016-03-01
The advent of phototransformable fluorescent proteins has led to significant advances in optical imaging, including the unambiguous tracking of cells over large spatiotemporal scales. However, these proteins typically require activating light in the UV-blue spectrum, which limits their in vivo applicability due to poor light penetration and associated phototoxicity on cells and tissue. We report that cyanine-based, organic dyes can be efficiently photoconverted by nonlinear excitation at the near infrared (NIR) window. Photoconversion likely involves singlet-oxygen mediated photochemical cleavage, yielding blue-shifted fluorescent products. Using SYTO62, a biocompatible and cell-permeable dye, we demonstrate photoconversion in a variety of cell lines, including depth-resolved labeling of cells in 3D culture. Two-photon photoconversion of cyanine-based dyes offer several advantages over existing photoconvertible proteins, including use of minimally toxic NIR light, labeling without need for genetic intervention, rapid kinetics, remote subsurface targeting, and long persistence of photoconverted signal. These findings are expected to be useful for applications involving rapid labeling of cells deep in tissue.
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Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.
Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W
2016-01-01
This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.
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Dunham, Richard M; Gordon, Shari N; Vaccari, Monica; Piatak, Michael; Huang, Yong; Deeks, Steven G; Lifson, Jeffrey; Franchini, Genoveffa; McCune, Joseph M
2013-02-01
Even in the setting of maximally suppressive antiretroviral therapy (ART), HIV persists indefinitely. Several mechanisms might contribute to this persistence, including chronic inflammation and immune dysfunction. In this study, we have explored a preclinical model for the evaluation of potential interventions that might serve to eradicate or to minimize the level of persistent virus. Given data that metabolic products of the inducible enzyme indoleamine 2,3-dioxygeanse (IDO) might foster inflammation and viral persistence, chronically simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques were treated with the IDO inhibitor 1-methyl tryptophan (1mT). Orally administered 1mT achieved targeted plasma levels, but did not impact tryptophan metabolism or decrease viral RNA or DNA in plasma or in intestinal tissues beyond levels achieved by ART alone. Animals treated with 1mT showed no difference in the levels of T cell activation or differentiation, or in the kinetics or magnitude of viral rebound following cessation of ART. Notwithstanding these negative results, our observations suggest that the chronically SIV-infected rhesus macaque on suppressive ART can serve as a tractable model in which to test and to prioritize the selection of other potential interventions designed to eradicate HIV in vivo. In addition, this model might be used to optimize the route and dose by which such interventions are administered and the methods by which their effects are monitored.
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Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics
2003-01-01
Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair. PMID:12975533
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Brown, Courtney K; Southerst, Danielle; Côté, Pierre; Shearer, Heather M; Randhawa, Kristi; Wong, Jessica J; Yu, Hainan; Varatharajan, Sharanya; Sutton, Deborah; Stern, Paula J; D'Angelo, Kevin; Dion, Sarah; Cox, Jocelyn; Goldgrub, Rachel; Stupar, Maja; Carroll, Linda J; Taylor-Vaisey, Anne
2016-02-01
The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip, thigh, and knee. We conducted a systematic review and searched MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text from January 1, 1990, to April 8, 2015, for randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effect of exercise on pain intensity, self-rated recovery, functional recovery, health-related quality of life, psychological outcomes, and adverse events. Random pairs of independent reviewers screened titles and abstracts and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria. Best evidence synthesis methodology was used. We screened 9494 citations. Eight RCTs were critically appraised, and 3 had low risk of bias and were included in our synthesis. One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a "wait and see" approach for patellofemoral pain syndrome. A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome. One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain. We found limited high-quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity. The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain. Further high-quality research is needed. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 st...
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The Role of Endocytosis during Morphogenetic Signaling
Gonzalez-Gaitan, Marcos; Jülicher, Frank
2014-01-01
Morphogens are signaling molecules that are secreted by a localized source and spread in a target tissue where they are involved in the regulation of growth and patterning. Both the activity of morphogenetic signaling and the kinetics of ligand spreading in a tissue depend on endocytosis and intracellular trafficking. Here, we review quantitative approaches to study how large-scale morphogen profiles and signals emerge in a tissue from cellular trafficking processes and endocytic pathways. Starting from the kinetics of endosomal networks, we discuss the role of cellular trafficking and receptor dynamics in the formation of morphogen gradients. These morphogen gradients scale during growth, which implies that overall tissue size influences cellular trafficking kinetics. Finally, we discuss how such morphogen profiles can be used to control tissue growth. We emphasize the role of theory in efforts to bridge between scales. PMID:24984777
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Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection
Gordon, Claire L.; Thome, Joseph J.C.; Igarashi, Suzu
2017-01-01
T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. PMID:28130404
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Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.
Gordon, Claire L; Miron, Michelle; Thome, Joseph J C; Matsuoka, Nobuhide; Weiner, Joshua; Rak, Michael A; Igarashi, Suzu; Granot, Tomer; Lerner, Harvey; Goodrum, Felicia; Farber, Donna L
2017-03-06
T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. @Gordon et al.
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Peña, Adrián F; Doronin, Alexander; Tuchin, Valery V; Meglinski, Igor
2014-08-01
The influence of a low-frequency electric field applied to soft biological tissues ex vivo at normal conditions and upon the topical application of optical clearing agents has been studied by optical coherence tomography (OCT). The electro-kinetic response of tissues has been observed and quantitatively evaluated by the double correlation OCT approach, utilizing consistent application of an adaptive Wiener filtering and Fourier domain correlation algorithm. The results show that fluctuations, induced by the electric field within the biological tissues are exponentially increased in time. We demonstrate that in comparison to impedance measurements and the mapping of the temperature profile at the surface of the tissue samples, the double correlation OCT approach is much more sensitive to the changes associated with the tissues' electro-kinetic response. We also found that topical application of the optical clearing agent reduces the tissues' electro-kinetic response and is cooling the tissue, thus reducing the temperature induced by the electric current by a few degrees. We anticipate that dcOCT approach can find a new application in bioelectrical impedance analysis and monitoring of the electric properties of biological tissues, including the resistivity of high water content tissues and its variations.
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Damouche, Abderaouf; Pourcher, Guillaume; Pourcher, Valérie; Benoist, Stéphane; Busson, Elodie; Lataillade, Jean-Jacques; Le Van, Mélanie; Lazure, Thierry; Adam, Julien; Favier, Benoit; Vaslin, Bruno; Müller-Trutwin, Michaela; Lambotte, Olivier; Bourgeois, Christine
2017-12-01
We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Persistent spin helix manipulation by optical doping of a CdTe quantum well
NASA Astrophysics Data System (ADS)
Passmann, F.; Anghel, S.; Tischler, T.; Poshakinskiy, A. V.; Tarasenko, S. A.; Karczewski, G.; Wojtowicz, T.; Bristow, A. D.; Betz, M.
2018-05-01
Time-resolved Kerr-rotation microscopy explores the influence of optical doping on the persistent spin helix in a [001]-grown CdTe quantum well at cryogenic temperatures. Electron spin-diffusion dynamics reveal a momentum-dependent effective magnetic field providing SU(2) spin-rotation symmetry, consistent with kinetic theory. The Dresselhaus and Rashba spin-orbit coupling parameters are extracted independently from rotating the spin helix with external magnetic fields applied parallel and perpendicular to the effective magnetic field. Most importantly, a nonuniform spatiotemporal precession pattern is observed. The kinetic-theory framework of spin diffusion allows for modeling of this finding by incorporating the photocarrier density into the Rashba (α) and the Dresselhaus (β3) parameters. Corresponding calculations are further validated by an excitation-density-dependent measurement. This work shows universality of the persistent spin helix by its observation in a II-VI compound and the ability to fine-tune it by optical doping.
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On the causes of persistent apical periodontitis: a review.
Nair, P N R
2006-04-01
Apical periodontitis is a chronic inflammatory disorder of periradicular tissues caused by aetiological agents of endodontic origin. Persistent apical periodontitis occurs when root canal treatment of apical periodontitis has not adequately eliminated intraradicular infection. Problems that lead to persistent apical periodontitis include: inadequate aseptic control, poor access cavity design, missed canals, inadequate instrumentation, debridement and leaking temporary or permanent restorations. Even when the most stringent procedures are followed, apical periodontitis may still persist as asymptomatic radiolucencies, because of the complexity of the root canal system formed by the main and accessory canals, their ramifications and anastomoses where residual infection can persist. Further, there are extraradicular factors -- located within the inflamed periapical tissue -- that can interfere with post-treatment healing of apical periodontitis. The causes of apical periodontitis persisting after root canal treatment have not been well characterized. During the 1990s, a series of investigations have shown that there are six biological factors that lead to asymptomatic radiolucencies persisting after root canal treatment. These are: (i) intraradicular infection persisting in the complex apical root canal system; (ii) extraradicular infection, generally in the form of periapical actinomycosis; (iii) extruded root canal filling or other exogenous materials that cause a foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue healing of the lesion. This article provides a comprehensive overview of the causative factors of non-resolving periapical lesions that are seen as asymptomatic radiolucencies post-treatment.
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Noninvasive assessment of peroxidative lung damage by HIPDM lung scanning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miniati, M.; Borrelli, E.; Monti, S.
1991-03-15
The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by the lungs whence it is effluxed at a slow exponential rate. In humans (normal non smokers), the mean residence time ({bar t}) of 123I-HIPDM, assessed by external detection, averages 7.2 {plus minus} 1.1 hrs. Persistence of HIPDM in lungs is significantly increased in asymptomatic smokers and, to a greater extent, in patients with ARDS. Since production of free oxygen radicals reportedly occurs as a consequence of smoke exposure and in the course of acute lung injury, the authors hypothesized that the prolonged persistence of HIPDM in the lungs ofmore » smokers and of patients with ARDS might reflect a peroxidative damage of lung tissue. They tested this hypothesis in rabbits since their baseline HIPDM lung clearance is similar to that of nonsmoking humans. In rabbits, acute lung injury was induced by phorbol myristate acetate. Three hrs after PMA administration, the animals received an i.v. bolus of {sup 131}I-HIPDM. Radioactivity over the chest was recorded for 2 hrs by gamma camera and HIPDM mean residence time in the lungs was computed. Thereafter, the animals were sacrificed and their lungs were removed to measure wet/dry weight ratio as index of lung edema and malondialdehyde (MDA) content as index of lipid peroxidation. HIPDM mean residence time was positively correlated with MDA level in lung tissue, but not with wet/dry weight ratio. Noninvasive assessment of HIPDM lung kinetics may then serve as specific in vivo marker of peroxidative lung injury.« less
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Carossino, Mariano; Loynachan, Alan T.; Canisso, Igor F.; Cook, R. Frank; Campos, Juliana R.; Nam, Bora; Go, Yun Young; Squires, Edward L.; Troedsson, Mats H. T.; Swerczek, Thomas; Del Piero, Fabio; Bailey, Ernest; Timoney, Peter J.
2017-01-01
ABSTRACT Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as the primary sites of EAV persistence, the viral host cell tropism and whether viral replication in carrier stallions occurs in the presence or absence of host inflammatory responses remain unknown. In this study, dual immunohistochemical and immunofluorescence techniques were employed to unequivocally demonstrate that the ampulla is the main EAV tissue reservoir rather than immunologically privileged tissues (i.e., testes). Furthermore, we demonstrate that EAV has specific tropism for stromal cells (fibrocytes and possibly tissue macrophages) and CD8+ T and CD21+ B lymphocytes but not glandular epithelium. Persistent EAV infection is associated with moderate, multifocal lymphoplasmacytic ampullitis comprising clusters of B (CD21+) lymphocytes and significant infiltration of T (CD3+, CD4+, CD8+, and CD25+) lymphocytes, tissue macrophages, and dendritic cells (Iba-1+ and CD83+), with a small number of tissue macrophages expressing CD163 and CD204 scavenger receptors. This study suggests that EAV employs complex immune evasion mechanisms that warrant further investigation. IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid populations. Therefore, the precise identification of tissue and cellular tropism of EAV is critical for understanding the molecular basis of viral persistence and for development of improved prophylactic or treatment strategies. This study significantly enhances our understanding of the EAV carrier state in stallions by unequivocally identifying the ampullae as the primary sites of viral persistence, combined with the fact that persistence involves continuous viral replication in fibrocytes (possibly including tissue macrophages) and T and B lymphocytes in the presence of detectable inflammatory responses, suggesting the involvement of complex viral mechanisms of immune evasion. Therefore, EAV persistence provides a powerful new natural animal model to study RNA virus persistence in the male reproductive tract. PMID:28424285
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Understanding the causes and consequences of measles virus persistence
Griffin, Diane E.; Lin, Wen-Hsuan W.; Nelson, Ashley N.
2018-01-01
Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10–14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity. PMID:29560260
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Understanding the causes and consequences of measles virus persistence.
Griffin, Diane E; Lin, Wen-Hsuan W; Nelson, Ashley N
2018-01-01
Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity.
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Zika Virus RNA Replication and Persistence in Brain and Placental Tissue
Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.
2017-01-01
Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260
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Persistent luminescence in powdered and ceramic polycrystalline Gd3Al2Ga3O12:Ce
NASA Astrophysics Data System (ADS)
Dosovitskiy, G.; Fedorov, A.; Mechinsky, V.; Borisevich, A.; Dosovitskiy, A.; Tret'jak, E.; Korjik, M.
2017-02-01
This paper studies powders of Gd3Ga3Al2O12:Ce, a promising scintillator composition, as a possible object for express pre-characterization of scintillation kinetics and level of persistent luminescence. Garnet phase powders with uniform microstructure, consisting of 1-2 μm grains, were obtained by co-precipitation approach. It was shown, that both scintillation decay time and presence of persistent luminescence are influenced by both powder thermal treatment temperature and strong Ga deficit.
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Polychlorinated biphenyls (PCBs) and methylmercury (CH3Hg+) are known toxicants which persist in the environment and accumulate in tissue. Studies to identify mechanisms of action associated with these toxicants have largely been conducted in vitro, and dosimetry comparisons acro...
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NASA Astrophysics Data System (ADS)
Ivanov, Andrei V.; Gradyushko, A. T.; Laptev, V. P.; Panferova, N. G.; Varlamov, V. P.; Klyashchitsky, B. A.; Reshetnickov, Andrei V.; Ponomarev, Gelii V.
1996-01-01
The kinetics of photosensitizer distribution and elimination have been studied using fluorescent methods in organs and tumors of A/Snell mice with embriocarcinoma inoculated into their thigh muscles for the porphyrin compound 2,4-di((alpha) -methoxyethyl)deuteroporphyrin-- IX (DMH, `Dimehin') and its complex with polysaccharide chitosan. DMH fluorescence differs in samples of liver and faeces which follows from the spectra comparison. DMH is metabolizable upon passing through liver into a form eliminated by the gastrointestinal tract as our pharmacokinetic data have shown. DMH has been found to be a short-term highly photodynamically efficient photosensitizer judging by combined analysis of our toxicological, pharmacokinetic and photodynamic research data. DMH-chitosan uptake and distribution studies have shown the complex's long-term persistence in blood circulation, high level accumulation in spleen and lungs, whereas there was no complex registered in tumors and other tissues following i.v. administration.
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Kinetics of interior loop formation in semiflexible chains.
Hyeon, Changbong; Thirumalai, D
2006-03-14
Loop formation between monomers in the interior of semiflexible chains describes elementary events in biomolecular folding and DNA bending. We calculate analytically the interior distance distribution function for semiflexible chains using a mean field approach. Using the potential of mean force derived from the distance distribution function we present a simple expression for the kinetics of interior looping by adopting Kramers theory. For the parameters, that are appropriate for DNA, the theoretical predictions in comparison with the case are in excellent agreement with explicit Brownian dynamics simulations of wormlike chain (WLC) model. The interior looping times (tauIC) can be greatly altered in the cases when the stiffness of the loop differs from that of the dangling ends. If the dangling end is stiffer than the loop then tauIC increases for the case of the WLC with uniform persistence length. In contrast, attachment of flexible dangling ends enhances rate of interior loop formation. The theory also shows that if the monomers are charged and interact via screened Coulomb potential then both the cyclization (tauc) and interior looping (tauIC) times greatly increase at low ionic concentration. Because both tauc and tauIC are determined essentially by the effective persistence length [lp(R)] we computed lp(R) by varying the range of the repulsive interaction between the monomers. For short range interactions lp(R) nearly coincides with the bare persistence length which is determined largely by the backbone chain connectivity. This finding rationalizes the efficacy of describing a number of experimental observations (response of biopolymers to force and cyclization kinetics) in biomolecules using WLC model with an effective persistence length.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Shawler, D.L.; Beauregard, J.; Halpern, S.E.
We have administered fifty-six 24 hr infusions of the anti-human T-cell monoclonal antibody T101 to 10 patients with cutaneous T-cell lymphoma (CTCL) and 6 patients with chronic lymphocytic leukemia (CLL) in doses of 10, 50, 100, 150, and 500 mg. The larger doses of T101 resulted in higher, more persistent serum T101 concentrations, and CTCL patients generally developed higher serum T101 levels than CLL patients given equivalent doses. The presence of host anti-mIgG antibodies prior to infusion was associated with decreased serum concentrations of T101. Treatments that demonstrated measurable serum T101 levels were also associated with in vivo T101 bindingmore » and cytodestruction of circulating target cells. Immunofluorescence analysis of bone marrow and lymph node biopsies in CLL, and skin biopsies in CTCL, suggested that T101 had reached extravascular tumor sites. Infusion of /sup 111/In-conjugated T101 showed uptake in the liver, spleen, lymph nodes, and (in CTCL) skin infiltrates. Our data demonstrate the tissue distribution of T101 and suggest that immunoconjugates of T101 with toxins, drugs, or radioisotopes may result in better therapeutic responses.« less
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Akutagawa, Takashi; Aoki, Shigehisa; Yamamoto-Rikitake, Mihoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji
2018-04-25
Early local tumor invasion in gastric cancer results in likely encounters between cancer cells and submucosal and subserosal adipose tissue, but these interactions remain to be clarified. Microenvironmental mechanical forces, such as fluid flow, are known to modulate normal cell kinetics, but the effects of fluid flow on gastric cancer cells are poorly understood. We analyzed the cell kinetics and chemosensitivity in gastric cancer using a simple in vitro model that simultaneously replicated the cancer-adipocyte interaction and physical microenvironment. Gastric cancer cells (MKN7 and MKN74) were seeded on rat adipose tissue fragment-embedded discs or collagen discs alone. To generate fluid flow, samples were placed on a rotatory shaker in a CO 2 incubator. Proliferation, apoptosis, invasion, and motility-related molecules were analyzed by morphometry and immunostaining. Proteins were evaluated by western blot analysis. Chemosensitivity was investigated by trastuzumab treatment. Adipose tissue and fluid flow had a positive synergistic effect on the proliferative potential and invasive capacity of gastric cancer cells, and adipose tissue inhibited apoptosis in these cells. Adipose tissue upregulated ERK1/2 signaling in gastric cancer cells, but downregulated p38 signaling. Notably, adipose tissue and fluid flow promoted membranous and cytoplasmic HER2 expression and modulated chemosensitivity to trastuzumab in gastric cancer cells. We have demonstrated that cancer-adipocyte interaction and physical microenvironment mutually modulate gastric cancer cell kinetics. Further elucidation of the microenvironmental regulation in gastric cancer will be very important for the development of strategies involving molecular targeted therapy.
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Audi, Said; Li, Zhixin; Capacete, Joseph; Liu, Yu; Fang, Wei; Shu, Laura G.; Zhao, Ming
2013-01-01
Introduction 99mTc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between 99mTc-Duramycin and the target tissue. Methods High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague Dawley rats. Target binding and biodistribution of 99mTc-duramycin was captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of 99mTc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of 99mTc-Duramycin in normal and ischemic myocardial tissue. Results 99mTc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to 99mTc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for 99mTc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9 fold reduction in binding affinity. Conclusion 99mTc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of 99mTc-Duramycin as a novel PE-binding agent. PMID:22534031
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Kinetics and tissue repair process following fractional bipolar radiofrequency treatment.
Kokolakis, G; von Eichel, L; Ulrich, M; Lademann, J; Zuberbier, T; Hofmann, M A
2018-05-15
Fractionated radiofrequency (RF) tissue tightening is an alternative method to fractionated laser treatment of skin wrinkling, laxity and acne scars, with reduced risk of scarring or persistent pigmentation. The aim of this study was to evaluate and quantify the wound healing process after RF treatment. 12 patients were treated with a 64-pin fractional bipolar RF device with 60 mJ/pin applied energy. Confocal laser scanning microscopy (CLSM) examination was performed on day 1, day 2, day 7 and day 14 after treatment. Clinical wound healing process was measured and expressed as a percentage. All patients developed erythema, mild edema and crusts at the treated areas. Two weeks after treatment clinical symptoms resolved. During ablation patients reported moderate pain. Directly after ablation microscopic ablation zones could be detected in CLSM. Measurement of MAZ at epidermis, dermo-epidermal junction and papilary dermis showed a constant diameter until two weeks after treatment. Re-epithelization of the MAZ could be detected already 1 week after treatment. However, 2 weeks after ablation the honeycomb pattern of the epidermis was not yet completely restored. Bipolar fractionated RF treatment demonstrates clinically a rapid wound healing response. The subepidermal remodelling process still ongoing after 14 days, showing new granulation tissue. Therefore, treatment intervals of at least 14 days should be recommended to allow completion of the remodelling process.
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Detection and Persistence of Vi Antigen in Tissues of Actively Immunized Mice1
Gaines, Sidney; Currie, Julius A.; Tully, Joseph G.
1965-01-01
Gaines, Sidney (Walter Reed Army Institute of Research, Washington, D.C.), Julius A. Currie, and Joseph G. Tully. Detection and persistence of Vi antigen in tissues of actively immunized mice. J. Bacteriol. 89:776–781. 1965.—The presence, distribution, and persistence of Vi antigen in mouse tissue was determined by means of active immunization tests with tissue extracts. Mice were injected intraperitoneally with purified Vi antigen or Vi-containing bacilli. At appropriate intervals, animals were killed, and saline extracts of their tissues were prepared. Mice were immunized with these extracts and challenged 6 days later with 10 ld50 of Salmonella typhosa Ty2. Protection was afforded by tissue extracts from Vi-injected mice, but not by normal tissue extracts. That the immunizing capacity of tissue extracts from Vi-injected mice was attributable to Vi antigen was affirmed by the demonstration that these extracts stimulated the production of Vi antibody in mice, coated erythrocytes for agglutination by Vi antiserum, and inhibited agglutination of Vi-sensitized red blood cells by known Vi antisera. Vi antigen could be detected in the liver and spleen of mice injected with as little as 1 μg. In mice given 150 μg, the antigen was still present in liver tissue 231 days later. PMID:14273660
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Tandon, Shishir; Pant, Ravi
2017-10-10
The phenylureas group includes persistent herbicides which are major pollutants to soil and water. Dissipation kinetics of diuron in different soils under sugarcane field conditions was investigated. Diuron was extracted with acetone and florisil solid phase extraction clean-up and characterized by high-performance liquid chromatography-UV. Diuron persisted for more than 100 days and dissipation followed monophasic first-order kinetics. Persistence was more in sandy loam compared to silty clay loam soil. Half-life of diuron in silty clay loam soil was 22.57 and 32.37 days and in sandy loam was 28.35 and 43.93 days at 2 and 4 kg ha-1applications, respectively. Average recovery in soil, bagasse, leaf-straw and juice ranged from 75.95% to 84.20%, 80.15% to 89.35%, 77.46% to 86.19% and 81.88% to 92.68%, respectively. The quantitation limits for soil, bagasse, leaf-straw and juice were 0.01, 0.03, 0.04 μg g -1 and 0.008 μg mL -1 , respectively. Application of diuron inhibited growth of soil microbes initially but they recovered later. At harvest, diuron residues were below maximum residue limits in all samples. The study revealed that under subtropical conditions, diuron is safe for use in weed management and would not pose any residual/environmental problem and that sugarcane crop could be used safe for human/animal consumption.
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NASA Astrophysics Data System (ADS)
Sadeghipour, Negar; Davis, Scott C.; Tichauer, Kenneth M.
2018-02-01
Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptors in vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing factor to correct for tissue optical property differences. In this study, the kinetic model used for paired-agent imaging analysis (i.e., simplified reference tissue model) is modified and tested in simulation and experimental data in a way that accounts for the scaling correction within the kinetic model fit to the data to ultimately extract an estimate of the targeted biomarker concentration.
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Thioesters for the in vitro evaluation of agents to image brain cholinesterases.
Macdonald, Ian R; Jollymore, Courtney T; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan
2013-06-01
Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.
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Perbellini, L; Mozzo, P; Brugnone, F; Zedde, A
1986-01-01
The physiologicomathematical model with eight compartments described allows the simulation of the absorbtion, distribution, biotransformation, excretion of an organic solvent, and the kinetics of its metabolites. The usual compartments of the human organism (vessel rich group, muscle group, and fat group) are integrated with the lungs, the metabolising tissues, and three other compartments dealing with the metabolic kinetics (biotransformation, water, and urinary compartments). The findings obtained by mathematical simulation of exposure to n-hexane were compared with data previously reported. The concentrations of n-hexane in alveolar air and in venous blood described both in experimental and occupational exposures provided a substantial validation for the data obtained by mathematical simulation. The results of the urinary excretion of 2,5-hexanedione given by the model were in good agreement with data already reported. The simulation of an exposure to n-hexane repeated five days a week suggested that the solvent accumulates in the fat tissue. The half life of n-hexane in fat tissue equalled 64 hours. The kinetics of 2,5-hexanedione resulting from the model suggest that occupational exposure results in the presence of large amounts of 2,5-hexanedione in the body for the whole working week. PMID:3790456
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Young, E J; Gomez, C I; Yawn, D H; Musher, D M
1979-01-01
By using mice infected with strains of Brucella abortus and Brucella melitensis we examined the histological responses to infection, the relationship of histology to persistence of organisms, and the relation of persistence of organisms to the acquisition of acquired cellular resistance (ACR). Infection with B. abortus resulted in well-formed granulomas in the livers, which persisted for more than 30 days. In contrast, infection with B. melitensis produced microabscesses in the livers which resolved before 30 days. The clearance of organisms from the tissues was also different. A total of 30 days after infection, large numbers of viable bacteria were recovered from the tissues of B. abortus-infected mice whereas bacteria were no longer recoverable from B. melitensis-infected animals. ACR to Listeria monocytogenes, another intracellular pathogen, persisted for more than 30 days in B. abortus-infected mice but waned rapidly in B. melitensis-infected animals. This disappearance of ACR due to B. melitensis paralleled the clearance of bacteria from the tissues. Images PMID:121113
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Hierarchy revealed in the specification of three skeletal fates by Sox9 and Runx2.
Eames, B Frank; Sharpe, Paul T; Helms, Jill A
2004-10-01
Across vertebrates, there are three principal skeletal tissues: bone, persistent cartilage, and replacement cartilage. Although each tissue has a different evolutionary history and functional morphology, they also share many features. For example, they function as structural supports, they are comprised of cells embedded in collagen-rich extracellular matrix, and they derive from a common embryonic stem cell, the osteochondroprogenitor. Occasionally, homologous skeletal elements can change tissue type through phylogeny. Together, these observations raise the possibility that skeletal tissue identity is determined by a shared set of genes. Here, we show that misexpression of either Sox9 or Runx2 can substitute bone with replacement cartilage or can convert persistent cartilage into replacement cartilage and vice versa. Our data also suggest that these transcription factors function in a molecular hierarchy in which chondrogenic factors dominate. We propose a binary molecular code that determines whether skeletal tissues form as bone, persistent cartilage, or replacement cartilage. Finally, these data provide insights into the roles that master regulatory genes play during evolutionary change of the vertebrate skeleton.
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Audi, Said; Li, Zhixin; Capacete, Joseph; Liu, Yu; Fang, Wei; Shu, Laura G; Zhao, Ming
2012-08-01
(99m)Tc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between (99m)Tc-Duramycin and the target tissue. High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague-Dawley rats. Target binding and biodistribution of (99m)Tc-duramycin were captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of (99m)Tc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of (99m)Tc-Duramycin in normal and ischemic myocardial tissue. (99m)Tc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to (99m)Tc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for (99m)Tc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9-fold reduction in binding affinity. (99m)Tc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of (99m)Tc-Duramycin as a novel PE-binding agent. Copyright © 2012 Elsevier Inc. All rights reserved.
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Lun'ko, O O; Isaiev, D S; Maxymiuk, O P; Kryshtal', O O; Isaieva, O V
2014-01-01
We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (I(NaP)) in hippocampal CA1 pyramidal neurons. Properties of I(NaP) were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We show that in neurons isolated with pronase E kinetic of activation and density of I(NaP) was unaltered. Enzymatic treatment with protease type XXIII did not alter I(NaP) activation but result in significant decrease in I(NaP) density. Our data indicates that enzymatic treatment using pronase E for neuron isolation is preferable for investigation of I(NaP).
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NASA Astrophysics Data System (ADS)
Khandkar, Mahendra D.; Stinchcombe, Robin; Barma, Mustansir
2017-01-01
We demonstrate the large-scale effects of the interplay between shape and hard-core interactions in a system with left- and right-pointing arrowheads <> on a line, with reorientation dynamics. This interplay leads to the formation of two types of domain walls, >< (A ) and <> (B ). The correlation length in the equilibrium state diverges exponentially with increasing arrowhead density, with an ordered state of like orientations arising in the limit. In this high-density limit, the A domain walls diffuse, while the B walls are static. In time, the approach to the ordered state is described by a coarsening process governed by the kinetics of domain-wall annihilation A +B →0 , quite different from the A +A →0 kinetics pertinent to the Glauber-Ising model. The survival probability of a finite set of walls is shown to decay exponentially with time, in contrast to the power-law decay known for A +A →0 . In the thermodynamic limit with a finite density of walls, coarsening as a function of time t is studied by simulation. While the number of walls falls as t-1/2, the fraction of persistent arrowheads decays as t-θ where θ is close to 1/4 , quite different from the Ising value. The global persistence too has θ =1/4 , as follows from a heuristic argument. In a generalization where the B walls diffuse slowly, θ varies continuously, increasing with increasing diffusion constant.
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Khandkar, Mahendra D; Stinchcombe, Robin; Barma, Mustansir
2017-01-01
We demonstrate the large-scale effects of the interplay between shape and hard-core interactions in a system with left- and right-pointing arrowheads <> on a line, with reorientation dynamics. This interplay leads to the formation of two types of domain walls, >< (A) and <> (B). The correlation length in the equilibrium state diverges exponentially with increasing arrowhead density, with an ordered state of like orientations arising in the limit. In this high-density limit, the A domain walls diffuse, while the B walls are static. In time, the approach to the ordered state is described by a coarsening process governed by the kinetics of domain-wall annihilation A+B→0, quite different from the A+A→0 kinetics pertinent to the Glauber-Ising model. The survival probability of a finite set of walls is shown to decay exponentially with time, in contrast to the power-law decay known for A+A→0. In the thermodynamic limit with a finite density of walls, coarsening as a function of time t is studied by simulation. While the number of walls falls as t^{-1/2}, the fraction of persistent arrowheads decays as t^{-θ} where θ is close to 1/4, quite different from the Ising value. The global persistence too has θ=1/4, as follows from a heuristic argument. In a generalization where the B walls diffuse slowly, θ varies continuously, increasing with increasing diffusion constant.
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Autocatalytic polymerization generates persistent random walk of crawling cells.
Sambeth, R; Baumgaertner, A
2001-05-28
The autocatalytic polymerization kinetics of the cytoskeletal actin network provides the basic mechanism for a persistent random walk of a crawling cell. It is shown that network remodeling by branching processes near the cell membrane is essential for the bimodal spatial stability of the network which induces a spontaneous breaking of isotropic cell motion. Details of the phenomena are analyzed using a simple polymerization model studied by analytical and simulation methods.
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Belfiore, Laurence A; Floren, Michael L; Belfiore, Carol J
2012-02-01
This research contribution addresses electric-field stimulation of intra-tissue mass transfer and cell proliferation in viscoelastic biomaterials. The unsteady state reaction-diffusion equation is solved according to the von Kármán-Pohlhausen integral method of boundary layer analysis when nutrient consumption and tissue regeneration occur in response to harmonic electric potential differences across a parallel-plate capacitor in a dielectric-sandwich configuration. The partial differential mass balance with diffusion and electro-kinetic consumption contains the Damköhler (Λ(2)) and Deborah (De) numbers. Zero-field and electric-field-sensitive Damköhler numbers affect nutrient boundary layer growth. Diagonal elements of the 2nd-rank diffusion tensor are enhanced in the presence of weak electric fields, in agreement with the formalism of equilibrium and nonequilibrium thermodynamics. Induced dipole polarization density within viscoelastic biomaterials is calculated via the real and imaginary components of the complex dielectric constant, according to the Debye equation, to quantify electro-kinetic stimulation. Rates of nutrient consumption under zero-field conditions are described by third-order kinetics that include local mass densities of nutrients, oxygen, and attached cells. Thinner nutrient boundary layers are stabilized at shorter dimensionless diffusion times when the zero-field intra-tissue Damköhler number increases above its initial-condition-sensitive critical value [i.e., {Λ(2)(zero-field)}(critical)≥53, see Eq. (23)], such that the biomaterial core is starved of essential ingredients required for successful proliferation. When tissue regeneration occurs above the critical electric-field-sensitive intra-tissue Damköhler number, the electro-kinetic contribution to nutrient consumption cannot be neglected. The critical electric-field-sensitive intra-tissue Damköhler number is proportional to the Deborah number. Copyright © 2011 Elsevier B.V. All rights reserved.
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Type 2 diabetes mellitus and exercise impairment.
Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G
2013-03-01
Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.
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2010-01-01
Background The goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient. Methods Experimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls. Results Solutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium. Conclusions These results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics. PMID:20055995
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Levitt, David G
2010-01-07
The goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient. Experimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls. Solutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium. These results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics.
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Virus-host interactions in persistently FMDV-infected cells derived from bovine pharynx
USDA-ARS?s Scientific Manuscript database
Foot-and-mouth disease virus (FMDV) produces a disease in cattle characterized by vesicular lesions and a persistent infection with asymptomatic low-level production of virus. Here we describe the establishment of a persistently infected primary cell culture derived from bovine pharynx tissue (PBPT)...
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Jødal, Lars; Jensen, Svend B; Nielsen, Ole L; Afzelius, Pia; Borghammer, Per; Alstrup, Aage K O; Hansen, Søren B
2017-01-01
Positron emission tomography (PET) is increasingly applied for infection imaging using [ 18 F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [ 18 F]FDG and three other PET tracers with relevance for infection imaging. A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [ 18 F]FDG, [ 68 Ga]Ga-citrate, [ 11 C]methionine, and/or [ 11 C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer. Irreversible uptake was found for [ 18 F]FDG and [ 68 Ga]Ga-citrate; reversible uptake was found for [ 11 C]methionine (two-tissue model) and [ 11 C]donepezil (one-tissue model). The uptake rate for [ 68 Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake). Net uptake rate for [ 18 F]FDG and distribution volume for [ 11 C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [ 11 C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis. The kinetics of the four studied tracers in infection was characterized. For clinical applications, [ 18 F]FDG remains the first-choice PET tracer. [ 11 C]methionine may have a potential for detecting soft tissue infections. [ 68 Ga]Ga-citrate and [ 11 C]donepezil were not found useful for imaging of osteomyelitis.
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PET/CT Imaging Reveals Unrivaled Placental Avidity for Glucose Compared to Other Tissues
Sawatzke, Alexander B.; Norris, Andrew W.; Spyropoulos, Fotios; Walsh, Susan A.; Acevedo, Michael R.; Hu, Shanming; Yao, Jianrong; Wang, Chunlin; Sunderland, John J.; Boles Ponto, Laura L.
2014-01-01
Introduction The goal of this study was to define the kinetics of glucose transport from maternal blood to placenta to fetus using real time imaging. Methods Positron emission tomography (PET) imaging of the glucose tracer [18F]fluorodeoxyglucose (FDG) was used to temporally and spatially define, in vivo, the kinetics of glucose transport from maternal blood into placentae and fetuses, in the late gestational gravid rat. Computed tomography (CT), with intravenous contrast, co-registered to the PET images allowed anatomic differentiation of placentae from fetal and maternal tissues. Results FDG was rapidly taken up by placentae and subsequently appeared in fetuses with minimal temporal lag. FDG standardized uptake values in placentae and fetuses approached that of maternal brain. In both anesthetized and awake dams, one quarter of the administered FDG ultimately was accrued in the collective fetuses and placentae. Accordingly, kinetic modeling demonstrated that the placentae had very high avidity for FDG, 2-fold greater than that of the fetus and maternal brain, when accounting for the fact that fetal FDG necessarily must first be taken up by placentae. Consistent with this, placental expression of glucose transporter 1 exceeded that of all other tissues. Discussion Fetal and placental tissues place a substantial glucose metabolic burden on the mother, owing to very high avidity of placentae for glucose coupled with the large relative mass of fetal and placental tissues. Conclusions The placenta has a tremendous capacity to uptake and transport glucose. PET/CT imaging is an ideal means to study metabolite transport kinetics in the fetoplacental unit. PMID:25555498
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Motility-Driven Glass and Jamming Transitions in Biological Tissues
NASA Astrophysics Data System (ADS)
Bi, Dapeng; Yang, Xingbo; Marchetti, M. Cristina; Manning, M. Lisa
2016-04-01
Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. To make quantitative predictions about glass transitions in tissues, we study a self-propelled Voronoi model that simultaneously captures polarized cell motility and multibody cell-cell interactions in a confluent tissue, where there are no gaps between cells. We demonstrate that the model exhibits a jamming transition from a solidlike state to a fluidlike state that is controlled by three parameters: the single-cell motile speed, the persistence time of single-cell tracks, and a target shape index that characterizes the competition between cell-cell adhesion and cortical tension. In contrast to traditional particulate glasses, we are able to identify an experimentally accessible structural order parameter that specifies the entire jamming surface as a function of model parameters. We demonstrate that a continuum soft glassy rheology model precisely captures this transition in the limit of small persistence times and explain how it fails in the limit of large persistence times. These results provide a framework for understanding the collective solid-to-liquid transitions that have been observed in embryonic development and cancer progression, which may be associated with epithelial-to-mesenchymal transition in these tissues.
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Free-living pathogens: life-history constraints and strain competition.
Caraco, Thomas; Wang, Ing-Nang
2008-02-07
Many pathogen life histories include a free-living stage, often with anatomical and physiological adaptations promoting persistence outside of host tissues. More durable particles presumably require that the pathogen metabolize more resources per particle. Therefore, we hypothesize functional dependencies, pleiotropic constraints, between the rate at which free-living particles decay outside of host tissues and other pathogen traits, including virulence, the probability of infecting a host upon contact, and pathogen reproduction within host tissues. Assuming that pathogen strains compete for hosts preemptively, we find patterns in trait dependencies predicting whether or not strain competition favors a highly persistent free-living stage.
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The role of stromal cells in the persistence of chronic inflammation
Naylor, A J; Filer, A; Buckley, C D
2013-01-01
Inflammation is an unstable state; it either resolves or persists. Inflammatory reactions often have a propensity for specific anatomical sites. Why inflammation persists with specific tissue tropism remains obscure. Increasing evidence suggests that stromal cells which define tissue architecture are the key cells involved, and therefore make attractive therapeutic targets. Research on stromal cells in general and fibroblasts in particular has so far been hampered by a lack of fibroblast-specific cell markers. This review highlights our increasing understanding of the role of fibroblasts in inflammation, and suggests that these cells provide the cellular basis for site specific chronic inflammation. PMID:23199320
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Li, Yuelin; Jiang, Zhang; Lin, Xiao -Min; ...
2015-01-30
Many potential industrial, medical, and environmental applications of metal nanorods rely on the physics and resultant kinetics and dynamics of the interaction of these particles with light. We report a surprising kinetics transition in the global melting of femtosecond laser-driven gold nanorod aqueous colloidal suspension. At low laser intensity, the melting exhibits a stretched exponential kinetics, which abruptly transforms into a compressed exponential kinetics when the laser intensity is raised. It is found the relative formation and reduction rate of intermediate shapes play a key role in the transition. Supported by both molecular dynamics simulations and a kinetic model, themore » behavior is traced back to the persistent heterogeneous nature of the shape dependence of the energy uptake, dissipation and melting of individual nanoparticles. These results could have significant implications for various applications such as water purification and electrolytes for energy storage that involve heat transport between metal nanorod ensembles and surrounding solvents.« less
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Persistent Step-Flow Growth of Strained Films on Vicinal Substrates
NASA Astrophysics Data System (ADS)
Hong, Wei; Lee, Ho Nyung; Yoon, Mina; Christen, Hans M.; Lowndes, Douglas H.; Suo, Zhigang; Zhang, Zhenyu
2005-08-01
We propose a model of persistent step flow, emphasizing dominant kinetic processes and strain effects. Within this model, we construct a morphological phase diagram, delineating a regime of step flow from regimes of step bunching and island formation. In particular, we predict the existence of concurrent step bunching and island formation, a new growth mode that competes with step flow for phase space, and show that the deposition flux and temperature must be chosen within a window in order to achieve persistent step flow. The model rationalizes the diverse growth modes observed in pulsed laser deposition of SrRuO3 on SrTiO3.
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NASA Astrophysics Data System (ADS)
Kobayashi, Hisataka
2017-02-01
Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Sprayable enzyme-activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. However, green fluorescent activatable probes suffers from interference from autofluorescence found in biological tissue. Dynamic imaging followed by the kinetic analysis could be detected local enzyme activity and used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied to detect tiny cancer foci. Serial fluorescence imaging was performed using various concentrations of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) which was sprayed on the peritoneal surface with tiny implants of SHIN3-dsRed ovarian cancer tumors. Temporal differences in signal between specific green fluorescence in cancer foci and non-specific autofluorescence in background tissue was measured and processed into three kinetic maps reflecting maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC), respectively. Especially at lower concentrations, kinetic maps derived from dynamic fluorescence imaging were clearly superior to unprocessed images for detection small cancer foci.
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Serafim, Angela; Bebianno, Maria João
2007-05-01
The aim of the present study was to determine the response of metallothionein (MT) during Cd accumulation and elimination in different tissues of the estuarine bivalve Ruditapes decussatus exposed to two nominal Cd concentrations (4 and 40 microg/L) for 40 d, followed by a depuration period of 50 d. Cadmium was accumulated in all tissues of R. decussatus at both exposure concentrations, and the accumulation was tissue dependent. Use of the kinetic model showed that in the gills and remaining tissues, Cd was assimilated faster at the beginning of the exposure and decreased with time, possibly limited by the diffusion rate of this metal within the cell. In the digestive gland, however, the Cd was continuously accumulated. This could reflect that the Cd uptake rate is considerably higher than the loss rate and, therefore, that this tissue has a higher capacity to accumulate Cd compared to the other two tissues. Moreover, the application of this kinetic model in the different subcellular fractions showed that the bioconcentration factor was significantly higher in the low-molecular-weight fraction (where MT is found), suggesting that this fraction binds Cd faster, with a high uptake rate (K(u) = 32/d), and eliminates this metal more slowly (K(1) = 0.005/d). During the depuration phase, MT decreased simultaneously with Cd elimination in all tissues, although with a shorter half-life. In conclusion, the MT response prevented Cd in the tissues of R. decussatus from interfering in the normal clam metabolism; therefore, MT acts as a detoxification mechanism of Cd.
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NASA Astrophysics Data System (ADS)
Shariati, Mohsen
2015-03-01
The growth of pyramidal and triangular beaded In2O3 nanocrystal chains by using oxygen-assisted thermal evaporation, substrate accommodation and condensation method has been articulated. Self-assembled In2O3 nanocrystal chains have been synthesized by the vapor-solid (VS) and vapor-liquid-solid (VLS) growth mechanism and also through controlling the kinetics factors (saturation ratio). A periodical one-dimensional (1-D) and persistent (0-D) growth was proposed to explain the formation of lateral nanostructures, and this formation aspect was ascribed to the alternate 1-D and 0-D growth. Preparing the needed growth factor, the In2O3 nanocrystal chains extended to several micrometers. The growth mechanism analysis was useful to realize the relation between the kinetics factors and the complex nanostructure. The morphology and size of nanocrystals intensively were changed by oxygen concentration and led to interesting photoluminescence property.
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Ramasubramanian, T; Paramasivam, M; Jayanthi, R; Nirmala, R
2016-01-01
Chlorantraniliprole 0.4 % GR has been in use for managing early shoot borer and top borer of sugarcane. Persistence and dissipation kinetics of granular formulation of chlorantraniliprole were studied in the soil of tropical sugarcane ecosystem by employing simple and sensitive analytical method. Limit of quantification of the method was 0.01 mg/kg and the recovery of chlorantraniliprole was in the range of 92.3-99.7 % with RSD of 1.14-3.0 %. The initial deposit of chlorantraniliprole in the soil was 0.513 and 1.031 mg/kg for the recommended (75 g a.i./ha) and double the recommended (150 g a.i./ha) doses, respectively. The residues were quantified up to 30 days after treatment irrespective of the doses applied. Half-life (t 1/2) was 6.60 and 6.73 days, respectively, for recommended and double the recommended doses of chlorantraniliprole.
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The physiological kinetics of nitrogen and the prevention of decompression sickness.
Doolette, D J; Mitchell, S J
2001-01-01
Decompression sickness (DCS) is a potentially crippling disease caused by intracorporeal bubble formation during or after decompression from a compressed gas underwater dive. Bubbles most commonly evolve from dissolved inert gas accumulated during the exposure to increased ambient pressure. Most diving is performed breathing air, and the inert gas of interest is nitrogen. Divers use algorithms based on nitrogen kinetic models to plan the duration and degree of exposure to increased ambient pressure and to control their ascent rate. However, even correct execution of dives planned using such algorithms often results in bubble formation and may result in DCS. This reflects the importance of idiosyncratic host factors that are difficult to model, and deficiencies in current nitrogen kinetic models. Models describing the exchange of nitrogen between tissues and blood may be based on distributed capillary units or lumped compartments, either of which may be perfusion- or diffusion-limited. However, such simplistic models are usually poor predictors of experimental nitrogen kinetics at the organ or tissue level, probably because they fail to account for factors such as heterogeneity in both tissue composition and blood perfusion and non-capillary exchange mechanisms. The modelling of safe decompression procedures is further complicated by incomplete understanding of the processes that determine bubble formation. Moreover, any formation of bubbles during decompression alters subsequent nitrogen kinetics. Although these factors mandate complex resolutions to account for the interaction between dissolved nitrogen kinetics and bubble formation and growth, most decompression schedules are based on relatively simple perfusion-limited lumped compartment models of blood: tissue nitrogen exchange. Not surprisingly, all models inevitably require empirical adjustment based on outcomes in the field. Improvements in the predictive power of decompression calculations are being achieved using probabilistic bubble models, but divers will always be subject to the possibility of developing DCS despite adherence to prescribed limits.
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A kinetic modeling of chondrocyte culture for manufacture of tissue-engineered cartilage.
Kino-Oka, Masahiro; Maeda, Yoshikatsu; Yamamoto, Takeyuki; Sugawara, Katsura; Taya, Masahito
2005-03-01
For repairing articular cartilage defects, innovative techniques based on tissue engineering have been developed and are now entering into the practical stage of clinical application by means of grafting in vitro cultured products. A variety of natural and artificial materials available for scaffolds, which permit chondrocyte cells to aggregate, have been designed for their ability to promote cell growth and differentiation. From the viewpoint of the manufacturing process for tissue-engineered cartilage, the diverse nature of raw materials (seeding cells) and end products (cultured cartilage) oblige us to design a tailor-made process with less reproducibility, which is an obstacle to establishing a production doctrine based on bioengineering knowledge concerning growth kinetics and modeling as well as designs of bioreactors and culture operations for certification of high product quality. In this article, we review the recent advances in the manufacturing of tissue-engineered cartilage. After outlining the manufacturing processes for tissue-engineered cartilage in the first section, the second and third sections, respectively, describe the three-dimensional culture of chondrocytes with Aterocollagen gel and kinetic model consideration as a tool for evaluating this culture process. In the final section, culture strategy is discussed in terms of the combined processes of monolayer growth (ex vivo chondrocyte cell expansion) and three-dimensional growth (construction of cultured cartilage in the gel).
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Laffon, Eric; Marthan, Roger
2017-11-01
To describe a three-time-point method for estimating kinetic parameters involved in 64 Cu-labeled Ramucirumab ( 64 Cu-NOTA-RamAb) trapping of VEGFR-2 positive lung tumors. Positron emission tomography (microPET) data of tumor-bearing mice for 64 Cu-NOTA-RamAb trapping in VEGFR-2 positive HCC4006 tumor were used, involving tissue activity measurements acquired at 3, 24 and 48 h post-injection, without and with administration of RamAb blocking dose. A kinetic model provided an analytical formula describing the tissue time-activity-curve, involving 64 Cu-NOTA-RamAb uptake (Ki), release rate constant (k R ) and fraction of free tracer in blood and interstitial volume (F). Fitting analytical formula outcomes on mean microPET data yielded values of the kinetic parameters: Ki = 0.0314/0.0123 gram of blood per hour per gram of tissue, k R = 0.0387/0.0313 h -1 and F = 0.2075/0.2007 gram of blood per gram of tissue, without/with RamAb blocking dose, respectively (R = 0.99999 for the graph displaying microPET versus theoretical data; P < .01). Three independent kinetic parameters (Ki, k R and F) can be assessed from three data points acquired at early, mid and late imaging, i.e., at 3, 24 and 48 h post-injection, for further characterization of 64 Cu-NOTA-RamAb trapping in VEGFR-2 positive lung tumors. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
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Kinetic examination of femoral bone modeling in broilers.
Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F
2014-05-01
Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute to subsequent pathology of the femoral head in fast-growing broilers.
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Jonasson, Kristin A; Russell, Anthony P; Vickaryous, Matthew K
2012-06-01
The persistence of the notochord into the skeletally mature life stage is characteristic of gekkotans, but is otherwise of rare occurrence among amniotes. The taxonomic diversity of Gekkota affords the opportunity to investigate the structure and development of this phylogenetically ancestral component of the skeleton, and to determine its basic characteristics. The gekkotan notochord spans almost the entire postcranial long axis and is characterized by a moniliform morphology with regularly alternating zones of chordoid and chondroid tissue. Chordoid tissue persists in the region of intervertebral articulations and occupies the cavitations that lie between the centra of the amphicoelous vertebrae. Chondroid tissue is restricted to zones in which the diameter of the notochord is reduced, corresponding to mid-vertebral locations. In the tail, these zones of chondroid tissue are associated with the autotomic fracture planes. Chondroid tissue first manifests during late embryogenesis, appears to differentiate from pre-existing chordoid tissue, and has the histological and histochemical characteristics of cartilage. Our observations lend support to the hypothesis that cartilage can be derived directly from notochordal tissue, and suggest that the latter may be an evolutionary and developmental precursor to chordate cartilage. The persistence of chordoid tissue in the intervertebral regions of amphicoelous vertebrae is consistent with a suite of paedomorphic traits exhibited by gekkotans and suggests that the typical hydrostatic nature of notochordal tissue may play a role in mechanically governing patterns of displacement between adjacent amphicoelous vertebrae that lack extensive centrum-to-centrum contact. Copyright © 2012 Wiley Periodicals, Inc.
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Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib.
Wodarz, Dominik; Garg, Naveen; Komarova, Natalia L; Benjamini, Ohad; Keating, Michael J; Wierda, William G; Kantarjian, Hagop; James, Danelle; O'Brien, Susan; Burger, Jan A
2014-06-26
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL). Characteristically, ibrutinib causes CLL cell redistribution from tissue sites into the peripheral blood during the initial weeks of therapy. To better characterize the dynamics of this redistribution phenomenon, we correlated serial lymphocyte counts with volumetric changes in lymph node and spleen sizes during ibrutinib therapy. Kinetic parameters were estimated by applying a mathematical model to the data. We found that during ibrutinib therapy, 1.7% ± 1.1% of blood CLL cells and 2.7% ± 0.99% of tissue CLL cells die per day. The fraction of the tissue CLL cells that was redistributed into the blood during therapy was estimated to be 23.3% ± 17% of the total tissue disease burden. These data indicate that the reduction of tissue disease burden by ibrutinib is due more to CLL cell death and less to egress from nodal compartments. © 2014 by The American Society of Hematology.
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NASA Astrophysics Data System (ADS)
Wu, Tao; Cheung, Tak-Hong; Yim, So-Fan; Qu, Jianan Y.
2010-03-01
A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.
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A strategy to determine operating parameters in tissue engineering hollow fiber bioreactors
Shipley, RJ; Davidson, AJ; Chan, K; Chaudhuri, JB; Waters, SL; Ellis, MJ
2011-01-01
The development of tissue engineering hollow fiber bioreactors (HFB) requires the optimal design of the geometry and operation parameters of the system. This article provides a strategy for specifying operating conditions for the system based on mathematical models of oxygen delivery to the cell population. Analytical and numerical solutions of these models are developed based on Michaelis–Menten kinetics. Depending on the minimum oxygen concentration required to culture a functional cell population, together with the oxygen uptake kinetics, the strategy dictates the model needed to describe mass transport so that the operating conditions can be defined. If cmin ≫ Km we capture oxygen uptake using zero-order kinetics and proceed analytically. This enables operating equations to be developed that allow the user to choose the medium flow rate, lumen length, and ECS depth to provide a prescribed value of cmin. When , we use numerical techniques to solve full Michaelis–Menten kinetics and present operating data for the bioreactor. The strategy presented utilizes both analytical and numerical approaches and can be applied to any cell type with known oxygen transport properties and uptake kinetics. PMID:21370228
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Ito, Hiroshi; Ikoma, Yoko; Seki, Chie; Kimura, Yasuyuki; Kawaguchi, Hiroshi; Takuwa, Hiroyuki; Ichise, Masanori; Suhara, Tetsuya; Kanno, Iwao
2017-05-01
Objectives In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compartment model (2-TCM), and binding parameters, including the total distribution volume (V T ), non-displaceable distribution volume (V ND ), and binding potential (BP ND ), can be determined from model parameters estimated by kinetic analysis. The stability of binding parameter estimates depends on the kinetic characteristics of radioligands. To describe these kinetic characteristics, we previously developed a two-phase graphic plot analysis in which V ND and V T can be estimated from the x-intercept of regression lines for early and delayed phases, respectively. In this study, we applied this graphic plot analysis to visual evaluation of the kinetic characteristics of radioligands for neuroreceptors, and investigated a relationship between the shape of these graphic plots and the stability of binding parameters estimated by the kinetic analysis with 2-TCM in simulated brain tissue time-activity curves (TACs) with various binding parameters. Methods 90-min TACs were generated with the arterial input function and assumed kinetic parameters according to 2-TCM. Graphic plot analysis was applied to these simulated TACs, and the curvature of the plot for each TAC was evaluated visually. TACs with several noise levels were also generated with various kinetic parameters, and the bias and variation of binding parameters estimated by kinetic analysis were calculated in each TAC. These bias and variation were compared with the shape of graphic plots. Results The graphic plots showed larger curvature for TACs with higher specific binding and slower dissociation of specific binding. The quartile deviations of V ND and BP ND determined by kinetic analysis were smaller for radioligands with slow dissociation. Conclusions The larger curvature of graphic plots for radioligands with slow dissociation might indicate a stable determination of V ND and BP ND by kinetic analysis. For investigation of the kinetics of radioligands, such kinetic characteristics should be considered.
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Free-living pathogens: life-history constraints and strain competition
Caraco, Thomas; Wang, Ing-Nang
2008-01-01
Many pathogen life histories include a free-living stage, often with anatomical and physiological adaptations promoting persistence outside of host tissues. More durable particles presumably require that the pathogen metabolize more resources per particle. Therefore, we hypothesize functional dependencies, pleiotropic constraints, between the rate at which free-living particles decay outside of host tissues and other pathogen traits, including virulence, the probability of infecting a host upon contact, and pathogen reproduction within host tissues. Assuming that pathogen strains compete for hosts preemptively, we find patterns in trait dependencies predicting whether or not strain competition favors a highly persistent free-living stage. PMID:18062992
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O'Sullivan, Finbarr; Muzi, Mark; Mankoff, David A; Eary, Janet F; Spence, Alexander M; Krohn, Kenneth A
2014-06-01
Most radiotracers used in dynamic positron emission tomography (PET) scanning act in a linear time-invariant fashion so that the measured time-course data are a convolution between the time course of the tracer in the arterial supply and the local tissue impulse response, known as the tissue residue function. In statistical terms the residue is a life table for the transit time of injected radiotracer atoms. The residue provides a description of the tracer kinetic information measurable by a dynamic PET scan. Decomposition of the residue function allows separation of rapid vascular kinetics from slower blood-tissue exchanges and tissue retention. For voxel-level analysis, we propose that residues be modeled by mixtures of nonparametrically derived basis residues obtained by segmentation of the full data volume. Spatial and temporal aspects of diagnostics associated with voxel-level model fitting are emphasized. Illustrative examples, some involving cancer imaging studies, are presented. Data from cerebral PET scanning with 18 F fluoro-deoxyglucose (FDG) and 15 O water (H2O) in normal subjects is used to evaluate the approach. Cross-validation is used to make regional comparisons between residues estimated using adaptive mixture models with more conventional compartmental modeling techniques. Simulations studies are used to theoretically examine mean square error performance and to explore the benefit of voxel-level analysis when the primary interest is a statistical summary of regional kinetics. The work highlights the contribution that multivariate analysis tools and life-table concepts can make in the recovery of local metabolic information from dynamic PET studies, particularly ones in which the assumptions of compartmental-like models, with residues that are sums of exponentials, might not be certain.
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USDA-ARS?s Scientific Manuscript database
Bovine viral diarrhea viruses are economically important pathogens of cattle. Most new infections are acquired from animals persistently infected with the virus. Surveillance programs rely on skin biopsies for detection of persistently infected cattle. The purpose of this study was to compare ant...
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Blind identification of the kinetic parameters in three-compartment models
NASA Astrophysics Data System (ADS)
Riabkov, Dmitri Y.; Di Bella, Edward V. R.
2004-03-01
Quantified knowledge of tissue kinetic parameters in the regions of the brain and other organs can offer information useful in clinical and research applications. Dynamic medical imaging with injection of radioactive or paramagnetic tracer can be used for this measurement. The kinetics of some widely used tracers such as [18F]2-fluoro-2-deoxy-D-glucose can be described by a three-compartment physiological model. The kinetic parameters of the tissue can be estimated from dynamically acquired images. Feasibility of estimation by blind identification, which does not require knowledge of the blood input, is considered analytically and numerically in this work for the three-compartment type of tissue response. The non-uniqueness of the two-region case for blind identification of kinetic parameters in three-compartment model is shown; at least three regions are needed for the blind identification to be unique. Numerical results for the accuracy of these blind identification methods in different conditions were considered. Both a separable variables least-squares (SLS) approach and an eigenvector-based algorithm for multichannel blind deconvolution approach were used. The latter showed poor accuracy. Modifications for non-uniform time sampling were also developed. Also, another method which uses a model for the blood input was compared. Results for the macroparameter K, which reflects the metabolic rate of glucose usage, using three regions with noise showed comparable accuracy for the separable variables least squares method and for the input model-based method, and slightly worse accuracy for SLS with the non-uniform sampling modification.
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Verstraeten, Natalie; Fauvart, Maarten
2016-01-01
Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—are collectively referred to as the “ESKAPE bugs.” They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro. We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. PMID:27185802
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KINETIC AND DYNAMIC ASPECTS OF ARSENIC TOXICITY
This project integrates research on aspects of the kinetic and dynamic behavior of arsenic. A PBPK model for arsenic will be developed using metabolism and disposition data from studies in mice. Retention of arsenic in the tissues following exposure to arsenic will be investigate...
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Maddur, Mohan S.; Kishore, Subodh; Gopalakrishna, S.; Singh, Nem; Suryanarayana, V. V.; Gajendragad, Mukund R.
2009-01-01
Despite their potential role in the spread of foot-and-mouth disease (FMD), the immune response and viral persistence in FMD virus (FMDV)-infected Indian buffaloes (Bubalus bubalis) have been unexplored. We found similar kinetics of neutralizing antibody responses in the sera and secretory fluids of buffaloes following experimental FMDV Asia 1 infection, but the lymphocyte-proliferative response in infected buffaloes was of low magnitude. Despite inducing a significant systemic and secretory immune response, viral persistence seems to be a common outcome in buffaloes following FMDV Asia 1 infection, which is associated with a weak cellular immune response. PMID:19828770
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NASA Astrophysics Data System (ADS)
Balankin, Alexander S.; Morales Matamoros, Oswaldo; Gálvez M., Ernesto; Pérez A., Alfonso
2004-03-01
The behavior of crude oil price volatility is analyzed within a conceptual framework of kinetic roughening of growing interfaces. We find that the persistent long-horizon volatilities satisfy the Family-Viscek dynamic scaling ansatz, whereas the mean-reverting in time short horizon volatilities obey the generalized scaling law with continuously varying scaling exponents. Furthermore we find that the crossover from antipersistent to persistent behavior is accompanied by a change in the type of volatility distribution. These phenomena are attributed to the complex avalanche dynamics of crude oil markets and so a similar behavior may be observed in a wide variety of physical systems governed by avalanche dynamics.
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Zheng, Bin; Bai, Yang; Chen, Hongbin; Pan, Huizhuo; Ji, Wanying; Gong, Xiaoqun; Wu, Xiaoli; Wang, Hanjie; Chang, Jin
2018-05-14
Optical imaging for biological applications is in need of more sensitive tool. Persistent luminescent nanophosphors enable highly sensitive in vivo optical detection and almost completely avoids tissue autofluorescence. Nevertheless, the actual persistent luminescent nanophosphors necessitates ex vivo activation before systemic operation, which severely restricted the use of long-term imaging in vivo. Hence, we introduced a novel generation of optical nanophosphors, based on (Zn2SiO4: Mn): Y3+, Yb3+, Tm3+ upconverting persistent luminescent nanophosphors, these nanophosphors can be excited in vivo through living tissues by highly penetrating near-infrared light. We can trace labeled tumor therapeutic macrophages in vivo after endocytosing these nanophosphors in vitro and follow macrophages biodistribution by a simple whole animal optical detection. These nanophosphors will open novel potentials for cell therapy research and for a variety of diagnosis applications in vivo.
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NASA Astrophysics Data System (ADS)
Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille
2014-04-01
Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.
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Scholz, Eberhard P; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A; Seemann, Gunnar
2013-01-01
Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits.
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Scholz, Eberhard P.; Carrillo-Bustamante, Paola; Fischer, Fathima; Wilhelms, Mathias; Zitron, Edgar; Dössel, Olaf; Katus, Hugo A.; Seemann, Gunnar
2013-01-01
Inhibition of the atrial ultra-rapid delayed rectifier potassium current (I Kur) represents a promising therapeutic strategy in the therapy of atrial fibrillation. However, experimental and clinical data on the antiarrhythmic efficacy remain controversial. We tested the hypothesis that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of channel blockade. A mathematical description of I Kur blockade was introduced into Courtemanche-Ramirez-Nattel models of normal and remodeled atrial electrophysiology. Effects of five model compounds with different kinetic properties were analyzed. Although a reduction of dominant frequencies could be observed in two dimensional tissue simulations for all compounds, a reduction of spiral wave activity could be only be detected in two cases. We found that an increase of the percent area of refractory tissue due to a prolongation of the wavelength seems to be particularly important. By automatic tracking of spiral tip movement we find that increased refractoriness resulted in rotor extinction caused by an increased spiral-tip meandering. We show that antiarrhythmic effects of I Kur inhibitors are dependent on kinetic properties of blockade. We find that an increase of the percent area of refractory tissue is the underlying mechanism for an increased spiral-tip meandering, resulting in the extinction of re-entrant circuits. PMID:24376659
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Enantioselective Biotransformation of Chiral Persistent Organic Pollutants.
Zhang, Ying; Ye, Jing; Liu, Min
2017-01-01
Enantiomers of chiral compounds commonly undergo enantioselective transformation in most biologically mediated processes. As chiral persistent organic pollutants (POPs) are extensively distributed in the environment, differences between enantiomers in biotransformation should be carefully considered to obtain exact enrichment and specific health risks. This review provides an overview of in vivo biotransformation of chiral POPs currently indicated in the Stockholm Convention and their chiral metabolites. Peer-reviewed journal articles focused on the research question were thoroughly searched. A set of inclusion and exclusion criteria were developed to identify relevant studies. We mainly compared the results from different animal models under controlled laboratory conditions to show the difference between enantiomers in terms of distinct transformation potential. Interactions with enzymes involved in enantioselective biotransformation, especially cytochrome P450 (CYP), were discussed. Further research areas regarding this issue were proposed. Limited evidence for a few POPs has been found in 30 studies. Enantioselective biotransformation of α-hexachlorocyclohexane (α-HCH), chlordane, dichlorodiphenyltrichloroethane (DDT), heptachlor, hexabromocyclododecane (HBCD), polychlorinated biphenyls (PCBs), and toxaphene, has been investigated using laboratory mammal, fish, bird, and worm models. Tissue and excreta distributions, as well as bioaccumulation and elimination kinetics after administration of racemate and pure enantiomers, have been analyzed in these studies. Changes in enantiomeric fractions have been considered as an indicator of enantioselective biotransformation of chiral POPs in most studies. Results of different laboratory animal models revealed that chiral POP biotransformation is seriously affected by chirality. Pronounced results of species-, tissue-, gender-, and individual-dependent differences are observed in in vivo biotransformation of chiral POPs. Enantioselective biotransformation of chiral POPs is dependent on enzyme amounts and activities. However, the role of cytochrome P450 in enantioselective biotransformation has not yet been confirmed. Currently available data on biotransformation of chiral POPs provide a preliminary understanding of the fate of chiral compounds in organisms. Further detailed studies of species-dependent biotransformation pathway and molecular mechanism in various animal models should be performed to comprehensively understand chiral POP biotransformation.
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2014-01-01
Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an effect of crystalline form (anatase vs. rutile) on total Ti recovery. Conclusion Overall, the results of the present oral and IV study indicates very low oral bioavailability and slow tissue elimination. Limited uptake in combination with slow elimination might result in the long run in potential tissue accumulation. PMID:24993397
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Magalhães, R; Ferreira, V; Brandão, T R S; Palencia, R Casquete; Almeida, G; Teixeira, P
2016-08-01
This study aimed to investigate the effect of different conditions, including temperature (37 °C, 22 °C, and 4 °C), NaCl concentrations (2.5%, 4%, and 8%), and acidity (pH = 5), on the growth response of persistent and non-persistent isolates of Listeria monocytogenes. The resistance to two common sanitizers (benzalkonium chloride and hydrogen peroxide) was also investigated. A selected group of 41 persistent and non-persistent L. monocytogenes isolates recovered from three cheese processing plants during a previous longitudinal study was assembled. Average lag time was similar for persistent and non-persistent isolates grown at 37 °C, 22 °C and 4 °C but significantly shorter (p < 0.05) for persistent isolates grown at 2.5%, 4% and 8% NaCl, and at pH 5. Average growth rates were significantly higher (p < 0.05) for persistent than for non-persistent isolates when grown at 22 °C, 2.5%, 4% and 8% NaCl, and at pH 5. These results suggest that persistent strains may be better adapted to grow under stressful conditions frequently encountered in food processing environments than non-persistent strains. No relation between persistence and resistance to the tested sanitizers was found. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Rapid wall relaxation in elongating tissues. [Glycine max (L. ); Pisum sativum L
DOE Office of Scientific and Technical Information (OSTI.GOV)
Matyssek, R.; Maruyama, S.; Boyer, J.S.
1988-01-01
Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max (L.) Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, the authors investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. The authors found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached tomore » the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species.« less
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Goldoni, Matteo; Caglieri, Andrea; Poli, Diana; Vettori, Maria Vittoria; Corradi, Massimo; Apostoli, Pietro; Mutti, Antonio
2006-03-15
Chromium speciation has attracted attention because of the different toxicity of Cr(III), which is considered relatively non-toxic, and Cr(VI), which can cross cell membranes mainly as a chromate anion and has been classified as a class I human carcinogen. The aims of the present study were to measure soluble Cr(VI) levels in environmental samples, to develop a simple method of quantifying Cr(VI) in exhaled breath condensate (EBC), and to follow the kinetics of EBC Cr(VI) in chrome plating workers.Personal air samples were collected from 10 chrome platers; EBC was collected from the same workers immediately after the work shift on Tuesday and before the work shift on the following Wednesday. Environmental and EBC Cr(VI) levels were determined by means of colorimetry and electrothermal absorption atomic spectrometry, respectively.The method of detecting Cr(VI) in environmental air was based on the extraction of the Cr(VI)-diphenylcarbazide (Cr(VI)-DPC) complex in 1-butanol, whereas EBC Cr(VI) was determined using a solvent extraction of Cr(VI) as an ion pair with tetrabutylammonium ion, and subsequent direct determination of the complex (Cr(VI)-DPC) in EBC.Kinetic data showed that airborne Cr(VI) was reduced by 50% in airway lining fluid sampled at the end of exposure and that there was a further 50% reduction after about 15 h. The persistence of Cr(VI) in EBC supports the use of EBC in assessing target tissue levels of Cr(VI).
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Joint pain and Doppler-detectable bubbles in altitude (Hypobaric) decompression
NASA Technical Reports Server (NTRS)
Powell, Michael R.
1993-01-01
The observation that altitude decompression sickness (DCS) is associated with pain in the lower extremities is not new, although it is not a consistent finding. DCS in divers is generally in the upper body, an effect often attributed to non-loading of the body while immersed. In caisson workers, DCS is reported more in the lower extremities. Surprisingly, many researchers do not mention the location of DCS joint pain, apparently considering it to be random. This is not the case for the tissue ratios encountered in studying decompression associated with simulated EVA. In NASA/JSC tests, altitude DCS generally presented first in either the ankle, knee, or hip (83 percent = 73/88). There was a definite statistical relation between the maximum Spencer precordial Doppler Grade and the incidence of DCS in the extremity, although this is not meant to imply a casual relation between circulating gas bubbles and joint pain. The risk of DCS with Grade 4 was considerably higher than that of Grades 0 to 3. The DCS risk was independent of the 'tissue ratio.' There was a predominance of lower extremity DCS even when exercise was performed with the upper body. The reason for these locations we hypothesize to be attributed to the formation of tissue gas micronuclei from kinetic and tensile forces (stress-assisted nucleation) and are the result of the individuals ambulating in a 1g environment. Additionally, since these showers of Doppler bubbles can persist for hours, it is difficult to imagine that they are emanating solely from tendons and ligaments, the supposed site of joint pain. This follows from Henry's law linking the volume of joint tissue (the solvent) and the solubility coefficient of inert gas; there is volumetrically insufficient connective tissue to produce the prolonged release of gas bubbles. If gas bubbles are spawned and released from connective tissue, their volume is increased by those from muscle tissue. Therefore, the nexus between Doppler-detectable gas bubbles and joint-pain decompression sickness is essentially a statistical, rather than a direct, one.
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NASA Astrophysics Data System (ADS)
Monica Bricelj, V.; Cembella, Allan D.; Laby, David
2014-05-01
Surfclams, Spisula solidissima, pose a particular health risk for human consumption as they are characterized by accumulation of extremely high levels of toxins associated with paralytic shellfish poisoning (PSP), slow toxin elimination and an extremely high post-ingestive capacity for toxin bioconversion. Surfclam populations experience a wide range of temperatures along the NW Atlantic continental shelf, and are undergoing range contraction that has been attributed to global warming. In this study the influence of temperature (5, 12 and 21 °C) on detoxification kinetics of individual PSP toxins in two tissue compartments of juvenile surfclams (∼35 mm shell length) was determined under controlled laboratory conditions, over prolonged (2.4 months) depuration. Clams were toxified with a representative regional Gulf of Maine isolate of the dinoflagellate Alexandrium fundyense of known toxin profile, allowing tracking of changes in toxin composition and calculated toxicity in surfclam tissues. The visceral mass detoxified at all temperatures, although toxin loss rate increased with increasing temperature. In contrast, total toxin content and calculated toxicities in other tissues remained constant or even increased during depuration, suggesting a physiological or biochemical toxin-retention mechanism in this tissue pool and temperature-independent detoxification. In vivo toxin compositional changes in surfclam tissues found in this study provide evidence of specific toxin conversion pathways, involving both reductive and decarbamoylation pathways. We conclude that such toxin biotransformations, especially in non-visceral tissues, may introduce a discrepancy in describing kinetics of total toxicity (in saxitoxin equivalents [STXeq]) of S. solidissima over prolonged detoxification. Nevertheless, use of total toxicity values generated by routine regulatory monitoring based upon mouse bioassays or calculated from chemical analytical determination of molar toxin concentrations is adequate for first-order modeling of toxin kinetics in this species. Furthermore, the differential detoxification response of viscera and other tissues in relation to temperature emphasizes the need for two-compartment modeling to describe the fate of PSP toxins in this species. Finally, key parameters were identified that may prove useful in hindcasting the timing of toxic blooms or new toxin input in deep offshore waters where routine monitoring of toxic phytoplankton is impractical.
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The Locomotion of Mouse Fibroblasts in Tissue Culture
Gail, Mitchell H.; Boone, Charles W.
1970-01-01
Time-lapse cinematography was used to investigate the motion of mouse fibroblasts in tissue culture. Observations over successive short time intervals revealed a tendency for the cells to persist in their direction of motion from one 2.5 hr time interval to the next. Over 5.0-hr time intervals, however, the direction of motion appeared random. This fact suggested that D, the diffusion constant of a random walk model, might serve to characterize cellular motility if suitably long observation times were used. We therefore investigated the effect of “persistence” on the pure random walk model, and we found theoretically and confirmed experimentally that the motility of a persisting cell could indeed be characterized by an augmented diffusion constant, D*. A method for determining confidence limits on D* was also developed. Thus a random walk model, modified to comprehend the persistence effect, was found to describe the motion of fibroblasts in tissue culture and to provide a numerical measure of cellular motility. PMID:5531614
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Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure.
Khan, Shahzada; Telwatte, Sushama; Trapecar, Martin; Yukl, Steven; Sanjabi, Shomyseh
2017-11-01
The single greatest challenge to an HIV cure is the persistence of latently infected cells containing inducible, replication-competent proviral genomes, which constitute only a small fraction of total or infected cells in the body. Although resting CD4 + T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4 + T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues. The mechanisms by which latency is established and maintained will likely depend on the location and cytokine milieu surrounding the latently infected cells in each compartment. Therefore, successful HIV cure strategies require identification and characterization of the exact cell types that support viral persistence, particularly in the gut. In this review, we describe the seeding of the latent HIV reservoir in the gut mucosa; highlight the evidence for compartmentalization and depletion of T cells; summarize the immunologic consequences of HIV infection within the gut milieu; propose how the damaged gut environment may promote the latent HIV reservoir; and explore several immune cell targets in the gut and their place on the path toward HIV cure.
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Li, Z; Kelley, C; Collins, F; Rouse, D; Morris, S
1998-04-01
The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues.
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Michiels, Joran Elie; Van den Bergh, Bram; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan
2016-08-01
Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-are collectively referred to as the "ESKAPE bugs." They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review.
Yu, Hainan; Randhawa, Kristi; Côté, Pierre; Optima Collaboration
2016-07-01
Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of physical agents for the management of lower-limb soft tissue injuries had a high risk of bias. High-quality RCTs are still needed to assess the effectiveness of physical agents for managing the broad range of lower-limb soft tissue injuries. The effectiveness of most interventions remains unclear. Level of Evidence Therapy, 1a. Protocol registered July 10, 2014 with PROSPERO (CRD42014010621). J Orthop Sports Phys Ther 2016;46(7):523-554. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6521.
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Pfitzner, Michael; Schlothauer, Jan C; Bastien, Estelle; Hackbarth, Steffen; Bezdetnaya, Lina; Lassalle, Henri-Pierre; Röder, Beate
2016-06-01
Singlet oxygen observation is considered a valuable tool to assess and optimize PDT treatment. In complex systems, such as tumors in vivo, only the direct, time-resolved singlet oxygen luminescence detection can give reliable information about generation and interaction of singlet oxygen. Up to now, evaluation of kinetics was not possible due to insufficient signal-to-noise ratio. Here we present high signal-to-noise ratio singlet oxygen luminescence kinetics obtained in mouse tumor model under PDT relevant conditions. A highly optimized system based on a custom made laser diode excitation source and a high aperture multi-furcated fiber, utilizing a photomultiplier tube with a multi photon counting device was used. Luminescence kinetics with unsurpassed signal-to-noise ratio were gained from tumor bearing nude mice in vivo upon topic application, subcutaneous injection as well as intravenous injection of different photosensitizers (chlorin e6 and dendrimer formulations of chlorin e6). Singlet oxygen kinetics in appropriate model systems are discussed to facilitate the interpretation of complex kinetics obtained from in vivo tumor tissue. This is the first study addressing the complexity of singlet oxygen luminescence kinetics in tumor tissue. At present, further investigations are needed to fully explain the processes involved. Nevertheless, the high signal-to-noise ratio proves the applicability of direct time-resolved singlet oxygen luminescence detection as a prospective tool for monitoring photodynamic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.
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Sarras, Michael P.; Leontovich, Alexey A.; Olsen, Ansgar S.; Intine, Robert V.
2013-01-01
As previously reported by our lab streptozocin-induced Diabetes mellitus (DM) in adult zebrafish results in an impairment of tissue regeneration as monitored by caudal fin regeneration. Following streptozocin withdrawal, a recovery phase occurs to re-establish euglycemia, via pancreatic beta-cell regeneration. However, DM-associated impaired fin regeneration continues indefinitely in the metabolic memory state (MM) allowing for subsequent molecular analysis of the underlying mechanisms of MM. This study focuses on elucidating the molecular basis that explains the DM-associated impaired fin regeneration and why it persists into the MM state with the aim of better understanding MM. Using a combination of microarray analysis and bioinformatics approaches our study found that of the 14,900 transcripts analyzed, aberrant expression of 71 genes relating to tissue developmental and regeneration processes were identified in DM fish and the altered expression of these 71 genes persisted in MM fish. Key regulatory genes of major development, and signal transduction pathways were identified among this group of 71. The aberrant expression of key regulatory genes in the DM state that persist into the MM state provides a plausible explanation for how hyperglycemia induced impaired fin regeneration in the adult zebrafish DM/MM model. PMID:23438205
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Hu, Ting; Yang, Pei; Zhu, Hongmei; Chen, Xinlian; Xie, Xiaoyan; Yang, Mei; Liu, Shanling; Wang, He
2015-04-02
Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown. In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution. A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05). The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.
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Bertelli, A A; Giovannini, L; Stradi, R; Urien, S; Tillement, J P; Bertelli, A
1998-01-01
In view of the increasing interest in the biological activity of resveratrol, one of the components of red wine which is considered to be one of the main ingredients responsible for the beneficial effect of wine on human health, we have studied plasma kinetics and tissue bioavailability of this compound after red wine oral administration in rats. Plasma pharmacokinetics after oral administration of resveratrol could be described by an open one- or two-compartment model. Tissue concentrations show a significant cardiac bioavailability, and a strong affinity for the liver and kidneys.
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Fourier transform infrared spectroscopic analysis of cell differentiation
NASA Astrophysics Data System (ADS)
Ishii, Katsunori; Kimura, Akinori; Kushibiki, Toshihiro; Awazu, Kunio
2007-02-01
Stem cells and its differentiations have got a lot of attentions in regenerative medicine. The process of differentiations, the formation of tissues, has become better understood by the study using a lot of cell types progressively. These studies of cells and tissue dynamics at molecular levels are carried out through various approaches like histochemical methods, application of molecular biology and immunology. However, in case of using regenerative sources (cells, tissues and biomaterials etc.) clinically, they are measured and quality-controlled by non-invasive methods from the view point of safety. Recently, the use of Fourier Transform Infrared spectroscopy (FT-IR) has been used to monitor biochemical changes in cells, and has gained considerable importance. The objective of this study is to establish the infrared spectroscopy of cell differentiation as a quality control of cell sources for regenerative medicine. In the present study, as a basic study, we examined the adipose differentiation kinetics of preadipocyte (3T3-L1) and the osteoblast differentiation kinetics of bone marrow mesenchymal stem cells (Kusa-A1) to analyze the infrared absorption spectra. As a result, we achieved to analyze the adipose differentiation kinetics using the infrared absorption peak at 1739 cm-1 derived from ester bonds of triglyceride and osteoblast differentiation kinetics using the infrared absorption peak at 1030 cm-1 derived from phosphate groups of calcium phosphate.
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Grodner, Błażej; Napiórkowska, Mariola
2017-09-05
The article describes the inhibitory effect of two new aminoalkanol derivatives on the enzymatic kinetic of tissue non-specific alkaline phosphatase with use of capillary zone electrophoresis to evaluate the inhibitory effect. This technique allows to investigate of the enzymatic kinetic by the measure of the amounts of the substrate and product in the presence of compound (I) or (II) in the reaction mixture. The separation process was conducted using an eCAP fused-silica capillary. The detector was set at 200nm. The best parameters for the analysis were: 25mM sodium dihydrogen phosphate adjusted to pH=2.5, temperature 25°C, and voltage -15kV. Lineweaver-Burk plots were constructed and determined by comparison of the Km, of alkaline phosphatase in the presence of inhibitor (I) or (II) with the Km in a solution without inhibitor. The influence of replacement the propylamine group by the dimethylamine group on tissue non-specific alkaline phosphatase inhibition activity of new derivatives (I) and (II) was investigated. The tested compounds (I) and (II) were found to be tissue non-specific alkaline phosphatase inhibitors. Detailed kinetic studies indicated a competitive mode of inhibition against tissue non-specific alkaline phosphatase for compound (I) and non-competitive mode of inhibition for compound (II). Copyright © 2017 Elsevier B.V. All rights reserved.
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Krutkramelis, K.; Xia, B.; Oakey, J.
2016-01-01
PEG-based hydrogels have become widely used as drug delivery and tissue scaffolding materials. Common among PEG hydrogel-forming polymers are photopolymerizable acrylates such as polyethylene glycol diacrylate (PEGDA). Microfluidics and microfabrication technologies have recently enabled the miniaturization of PEGDA structures, thus enabling many possible applications for nano- and micro- structured hydrogels. The presence of oxygen, however, dramatically inhibits the photopolymerization of PEGDA, which in turn frustrates hydrogel formation in environments of persistently high oxygen concentration. Using PEGDA that has been emulsified in fluorocarbon oil via microfluidic flow focusing within polydimethylsiloxane (PDMS) devices, we show that polymerization is completely inhibited below critical droplet diameters. By developing an integrated model incorporating reaction kinetics and oxygen diffusion, we demonstrate that the critical droplet diameter is largely determined by the oxygen transport rate, which is dictated by the oxygen saturation concentration of the continuous oil phase. To overcome this fundamental limitation, we present a nitrogen micro-jacketed microfluidic device to reduce oxygen within the droplet, enabling the continuous on-chip photopolymerization of microscale PEGDA particles. PMID:26987384
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Kumar, N S; Kataria, J M; Koti, M; Dhama, K; Toroghi, R
2003-01-01
Polymerase chain reaction (PCR) assay was developed for the detection of Egg drop syndrome 1976 (EDS-76) virus in tissues, namely in the uterus, spleen and buffy coat. It was also used to study the persistence of the virus in tissues of experimentally infected layer birds. The PCR assay could detect as little as 10 fg of purified EDS-76 viral DNA. It also amplified the DNA of Fowl adenovirus serotypes 4 (FAV-4) and 8 (FAV-8). The virus persisted in the uterus up to day 21 post infection (p.i.). Detection of EDS-76 viral DNA in the buffy coat could be useful for studying the occurrence of the respective disease in layer bird flocks.
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Comparative experimental pharmacokinetics of benzimidazole derivatives.
Sergeeva, S A; Gulyaeva, I L
2008-12-01
Comparative study of experimental kinetics of distribution of benzimidazole derivatives (bemithyl, etomerzole, and thietazole) in organs and tissues was carried out after single and course treatment. The drugs intensely passed into organs and tissues from the blood after treatment by all protocols. Specific features of drug distribution were detected; for example, splenic tissue selectively accumulated thietazole during course treatment.
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Persistence of enteric viruses within oysters (Crassostrea virginica)
USDA-ARS?s Scientific Manuscript database
It is well known that water-borne enteric viruses are concentrated by bivalves. Why these viruses are selectively retained and remain infectious within shellfish tissues for extended periods is unknown. Our current hypothesis is that phagocytic hemocytes (blood cells) are a site of virus persiste...
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Photoactivated Composite Biomaterial for Soft Tissue Restoration in Rodents and in Humans
Nahas, Zayna; Reid, Branden; Coburn, Jeannine M.; Axelman, Joyce; Chae, Jemin J.; Guo, Qiongyu; Trow, Robert; Thomas, Andrew; Hou, Zhipeng; Lichtsteiner, Serge; Sutton, Damon; Matheson, Christine; Walker, Patricia; David, Nathaniel; Mori, Susumu; Taube, Janis M.; Elisseeff, Jennifer H.
2015-01-01
Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual’s social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials. PMID:21795587
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Gui, Duan; Yu, Riqing; He, Xuan; Tu, Qin; Wu, Yuping
2014-09-15
Eleven persistent organic pollutant (POP) compounds including ∑PCBs, ∑DDTs, ∑HCHs, aldrin, mirex, endrin, ∑CHLs, dieldrin, HCB, heptachlor and pentachlorobenzene were measured in the kidney, liver, muscle, melon and other tissues of Sousa chinensis stranded on the western coast of the Pearl River Estuary in China during 2007-2013. For most parameters of POPs measured, melon tissues contained the highest mean concentrations with the exception of aldrin, which was higher in the kidney and liver tissues. The concentrations of PCBs, DDTs, heptachlor and endrin in the melon tissue exhibited significant correlations with body length, whereas PCBs and heptachlor also displayed significant regression with age. Our studies showed hepatic concentrations of ∑DDTs, ∑HCHs and mirex in S. chinensis were generally higher than those found in cetaceans from other geographic locations. The high levels of POP residues in the testis of one male dolphin suggested an increasing risk of infertility in the species. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Gregory, William F.; Turnbull, Dylan; Rocchi, Mara; Meredith, Anna L.; Philbey, Adrian W.; Sharp, Colin P.
2017-01-01
Several adenoviruses are known to cause severe disease in veterinary species. Recent evidence suggests that canine adenovirus type 1 (CAV-1) persists in the tissues of healthy red foxes (Vulpes vulpes), which may be a source of infection for susceptible species. It was hypothesized that mustelids native to the UK, including pine martens (Martes martes) and Eurasian otters (Lutra lutra), may also be persistently infected with adenoviruses. Based on high-throughput sequencing and additional Sanger sequencing, a novel Aviadenovirus, tentatively named marten adenovirus type 1 (MAdV-1), was detected in pine marten tissues. The detection of an Aviadenovirus in mammalian tissue has not been reported previously. Two mastadenoviruses, tentatively designated marten adenovirus type 2 (MAdV-2) and lutrine adenovirus type 1 (LAdV-1), were also detected in tissues of pine martens and Eurasian otters, respectively. Apparently healthy free-ranging animals may be infected with uncharacterized adenoviruses with possible implications for translocation of wildlife. PMID:28749327
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Persistence of the primary vitreous in association with the morning glory disc anomaly.
Brown, G C; Gonder, J; Levin, A
1984-01-01
Two patients with the morning glory disc anomaly are reported. In one, fibrovascular stalk passed forward into the vitreous cavity, while in the second a persistent hyaloid artery extended anteriorly from a tuft of fibrous tissue to the posterior lens capsule. These cases suggest that in some eyes the morning glory disc anomaly occurs as a variant of persistent hyperplastic primary vitreous (PHPV).
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Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats
Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin
2014-01-01
Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict potential toxicological effects of silica nanoparticles on target organs. PMID:25565843
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Garver, K.A.; Conway, C.M.; Elliott, D.G.; Kurath, G.
2005-01-01
A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was used in a systematic study to analyze vaccine tissue distribution, persistence, expression patterns, and histopathologic effects. Vaccine plasmid pIHNw-G, containing the gene for the viral glycoprotein, was detected immediately after intramuscular injection in all tissues analyzed, including blood, but at later time points was found primarily in muscle tissue, where it persisted to 90 days. Glycoprotein expression was detected in muscle, kidney, and thymus tissues, with levels peaking at 14 days and becoming undetectable by 28 days. Histologic examination revealed no vaccine-specific pathologic changes at the standard effective dose of 0.1 ??g DNA per fish, but at a high dose of 50 ??g an increased inflammatory response was evident. Transient damage associated with needle injection was localized in muscle tissue, but by 90 days after vaccination no damage was detected in any tissue, indicating the vaccine to be safe and well tolerated. ?? Springer Science+Business Media, Inc. 2005.
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Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji
2013-01-01
Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants. PMID:23818778
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Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji
2013-01-01
Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.
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The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.
Nolan, David J; Rose, Rebecca; Rodriguez, Patricia H; Salemi, Marco; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S
2018-01-01
Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.
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Shiraki, K; Moriwaki, M; Kohno, T; Yanagihara, N; Miki, T
1999-01-01
A technique for incising thick retrolental fibrovascular tissue and extensive cyclitic membrane is reported in a case of anterior persistent hyperplastic primary vitreous. A membranectomy was performed in a 1-month-old post-lensectomy baby via a limbal approach. A sclerotome tip was hooked to cut through an extremely thick fibrovascular tissue by rotating the sclerotome by its grip. Sutherland microscissors (Grieshaber, Switzerland) and a vitrectomy cutter were used for further membranectomy. The baby was followed-up until age 18 months. A total of 3 membranectomy sessions were required because of rapid cyclitic membrane formation, severe centripetal retraction of the membrane on the ciliary processes, and posterior synechia. Thorough membranectomy and cutting the iris edge maintained a clear pupillary area during the 13-month postoperative period. Extremely thick retrolental fibrovascular tissue is a challenging condition that can be dealt with by delicate instrumentation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
De, Santanu, E-mail: santanujuphys91@gmail.com; Kumar, Kranti; Banerjee, A.
We have found that the geometrically frustrated spin chain compound Ca{sub 3}Co{sub 2}O{sub 6} belonging to Ising like universality class with uniaxial anisotropy shows kinetic arrest of first order intermediate phase (IP) to ferrimagnetic (FIM) transition. In this system, dc magnetization measurements followed by different protocols suggest the coexistence of high temperature IP with equilibrium FIM phase in low temperature. Formation of metastable state due to hindered first order transition has also been probed through cooling and heating in unequal field (CHUF) protocol. Kinetically arrested high temperature IP appears to persist down to almost the spin freezing temperature in thismore » system.« less
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Intracellular survival and vascular cell-to-cell transmission of Porphyromonas gingivalis
Li, Ling; Michel, Raynald; Cohen, Joshua; DeCarlo, Arthur; Kozarov, Emil
2008-01-01
Background Porphyromonas gingivalis is associated with periodontal disease and invades different cell types including epithelial, endothelial and smooth muscle cells. In addition to P. gingivalis DNA, we have previously identified live invasive bacteria in atheromatous tissue. However, the mechanism of persistence of this organism in vascular tissues remains unclear. Therefore, the objective of this study was to analyze the ability of intracellular P. gingivalis to persist for extended periods of time, transmit to and possibly replicate in different cell types. Results Using antibiotic protection assays, immunofluorescent and laser confocal microscopy, we found that after a prolonged intracellular phase, while P. gingivalis can still be detected by immunostaining, the intracellular organisms lose their ability to be recovered in vitro. Surprisingly however, intracellular P. gingivalis could be recovered in vitro upon co incubation with fresh vascular host cells. We then demonstrated that the organism was able to exit the initially infected host cells, then enter and multiply in new host cells. Further, we found that cell-to-cell contact increased the transmission rate but was not required for transmission. Finally, we found that the invasion of new host cells allowed P. gingivalis to increase its numbers. Conclusion Our results suggest that the persistence of vascular tissue-embedded P. gingivalis is due to its ability to transmit among different cell types. This is the first communication demonstrating the intercellular transmission as a likely mechanism converting latent intracellular bacteria from state of dormancy to a viable state allowing for persistence of an inflammatory pathogen in vascular tissue. PMID:18254977
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USDA-ARS?s Scientific Manuscript database
Understanding fecal indicator bacteria persistence in aquatic environments is important when making management decisions to improve instream water quality. Routinely, bacteria fate and transport models that rely on published kinetic decay constants are used to inform such decision making. The object...
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USDA-ARS?s Scientific Manuscript database
Immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in distinct microanatomic compartments of the bovine nasopharynx were investigated using quantitative RT-PCR and whole transcriptome microarray. Analysis of tissue samples obtained during ...
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Paparu, Pamela; Dubois, Thomas; Gold, Clifford S; Niere, Björn; Adipala, Ekwamu; Coyne, Daniel
2008-04-01
Two major biotic constraints to highland cooking banana (Musa spp., genome group AAA-EA) production in Uganda are the banana weevil Cosmopolites sordidus and the burrowing nematode Radopholus similis. Endophytic Fusarium oxysporum strains inoculated into tissue culture banana plantlets have shown control of the banana weevil and the nematode. We conducted screenhouse and field experiments to investigate persistence in the roots and rhizome of two endophytic Fusarium oxysporum strains, V2w2 and III4w1, inoculated into tissue-culture banana plantlets of highland cooking banana cultivars Kibuzi and Nabusa. Re-isolation of F. oxysporum showed that endophyte colonization decreased faster from the rhizomes than from the roots of inoculated plants, both in the screenhouse and in the field. Whereas rhizome colonization by F. oxysporum decreased in the screenhouse (4-16 weeks after inoculation), root colonization did not. However, in the field (17-33 weeks after inoculation), a decrease was observed in both rhizome and root colonization. The results show a better persistence in the roots than rhizomes of endophytic F. oxysporum strains V2w2 and III4w1.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Larsson, P.; Okla, L.; Collvin, L.
Levels of persistent pollutants, including PCBs, [Sigma]DDT, and [gamma]-hexachlorocyclohexane, were examined in a pike population inhabiting a eutrophic lake in southern Scandinavia. For females, levels of persistent pollutants decreased linearly with age, weight, or length. This decline was ascribed to the seasonal elimination of the lipophilic pollutants in roe, which contained up to 10 times higher fat levels compared to muscle and over 10 times the amounts of pollutants. Male pike contained higher levels of pollutants than females, probably due to the lower elimination via gonadal products, as germinal tissue constitutes only 2% of the male total body weight andmore » has a lower fat content than ovaries. Female germinal tissue can account for as much as 15% of the body weight. No major fat deposits other than those in germinal tissue were found in pike, which also had a low muscle fat content, suggesting that the importance of roe elimination in removing pollutants may be greater in pike than in salmonids. Uptake of persistent pollutants can vary greatly within a species, owing to differences in sex, age, and so forth, as well as between species, owing to differences in fat deposition strategies.« less
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NASA Astrophysics Data System (ADS)
Rinehart, Matthew T.; LaCroix, Jeffrey; Henderson, Marcus; Katz, David; Wax, Adam
2011-03-01
The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.
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Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.
Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst
2012-10-01
Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.
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Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle
2017-06-01
The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.
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Park, Soomin; Baek, Seung-Hun; Cho, Sang-Nae; Jang, Young-Saeng; Kim, Ahreum; Choi, In-Hong
2017-01-01
There is a substantial need for biomarkers to distinguish latent stage from active Mycobacterium tuberculosis infections, for predicting disease progression. To induce the reactivation of tuberculosis, we present a new experimental animal model modified based on the previous model established by our group. In the new model, the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. To identify the immunological status of the persistent and chronic stages, we analyzed immunological genes in lung tissues from mice infected with M. tuberculosis . Gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs; CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and (3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and CCL12) were noticeably increased in the chronic stage compared with the persistent stage by cDNA microarray ( p < 0.01, except CCL12) or RT-PCR ( p < 0.01). Therefore, these six significantly increased cytokines in lung tissue from the mouse tuberculosis model might be candidates for biomarkers to distinguish the two disease stages. This information can be combined with already reported potential biomarkers to construct a network of more efficient tuberculosis markers.
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Spiandore, Marie; Souilah-Edib, Mélanie; Piram, Anne; Lacoste, Alexandre; Josse, Denis; Doumenq, Pierre
2018-01-01
Chemical warfare agents have been used to incapacitate, injure or kill people, in a context of war or terrorist attack. It has previously been shown that hair could trap the sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. In order to investigate simulants persistency in hair after intense vapour exposure, their desorption kinetics were studied by using two complementary methods: hair residual content measurement and desorbed vapour monitoring. Results showed that both simulants were detected in air and could be recovered from hair 2 h after the end of exposure. Longer experiments with methyl salicylate showed that it could still be recovered from hair after 24 h. Our data were fitted with several kinetic models and best correlation was obtained with a bimodal first-order equation, suggesting a 2-step desorption kinetics model: initial fast regime followed by a slower desorption. 2-chloroethyl ethyl sulphide was also detected in the immediate environment after hair exposure for 2 h, and hair simulant content decreased by more than 80%. Our results showed that hair ability to release formerly trapped chemical toxics could lead to health hazard. Their persistency however confirmed the potentiality of hair analysis as a tool for chemical exposure assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Rapid growth in chemical and agrochemical industries during the past century have resulted in the release of large numbers of persistent organic chemicals (POCs) into the environment. Since POCs are prevalent in air, water, soil and tissue of organisms throughout the world and r...
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Jiang, Jingying; Boese, Matthias; Turner, Paul; Wang, Ruikang K
2008-01-01
By use of a Fourier transform infrared (FTIR) spectroscopic imaging technique, we examine the dynamic optical clearing processes occurring in hyperosmotically biocompatible agents penetrating into skin tissue in vitro. The sequential collection of images in a time series provides an opportunity to assess penetration kinetics of dimethyl sulphoxide (DMSO) and glycerol beneath the surface of skin tissue over time. From 2-D IR spectroscopic images and 3-D false color diagrams, we show that glycerol takes at least 30 min to finally penetrate the layer of epidermis, while DMSO can be detected in epidermis after only 4 min of being topically applied over stratum corneum sides of porcine skin. The results demonstrate the potential of a FTIR spectroscopic imaging technique as an analytical tool for the study of dynamic optical clearing effects when the bio-tissue is impregnated by hyperosmotically biocompatible agents such as glycerol and DMSO.
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Plasmid-dependent attachment of Agrobacterium tumefaciens to plant tissue culture cells.
Matthysse, A G; Wyman, P M; Holmes, K V
1978-11-01
Kinetic, microscopic, and biochemical studies show that virulent Ti (tumor inducing)-plasmid-containing strains of Agrobacterium attach to normal tobacco and carrot tissue culture cells. Kinetic studies showed that virulent strains of A. tumefaciens attach to the plant tissue culture cells in increasing numbers during the first 1 to 2 h of incubation of the bacteria with the plant cells. Five Ti-plasmid-containing virulent Agrobacterium strains showed greater attachment to tobacco cells than did five avirulent strains. Light and scanning electron microscopic observations confirmed that virulent strains showed little attachment. Bacterial attachment was blocked by prior incubation of the plant cells with lipopolysaccharide extracted from A. tumefaciens, but not from A. radiobacter, suggesting that bacterial lipopolysaccharide is one of the components involved in the attachment process. At least one other bacterial product may be required for attachment in tissue culture because the virulent A. tumefaciens NT1, which lacks the Ti plasmid, does not itself attach to tobacco cells, but its lipopolysaccharide does inhibit the attachment of virulent strains.
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Movement disorders secondary to craniocerebral trauma.
Krauss, Joachim K
2015-01-01
Over the past few decades it has been recognized that traumatic brain injury may result in various movement disorders. In survivors of severe head injury, post-traumatic movement disorders were reported in about 20%, and they persisted in about 10% of patients. The most frequent persisting movement disorder in this population is kinetic cerebellar outflow tremor in about 9%, followed by dystonia in about 4%. While tremor is associated most frequently with cerebellar or mesencephalic lesions, patients with dystonia frequently have basal ganglia or thalamic lesions. Moderate or mild traumatic brain injury only rarely causes persistent post-traumatic movement disorders. It appears that the frequency of post-traumatic movement disorders overall has been declining which most likely is secondary to improved treatment of brain injury. In patients with disabling post-traumatic movement disorders which are refractory to medical treatment, stereotactic neurosurgery can provide long-lasting benefit. While in the past the primary option for severe kinetic tremor was thalamotomy and for dystonia thalamotomy or pallidotomy, today deep brain stimulation has become the preferred treatment. Parkinsonism is a rare consequence of single head injury, but repeated head injury such as seen in boxing can result in chronic encephalopathy with parkinsonian features. While there is still controversy whether or not head injury is a risk factor for the development of Parkinson's disease, recent studies indicate that genetic susceptibility might be relevant. © 2015 Elsevier B.V. All rights reserved.
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Hemocytes Are Sites of Enteric Virus Persistence within Oysters ▿
Provost, Keleigh; Dancho, Brooke A.; Ozbay, Gulnihal; Anderson, Robert S.; Richards, Gary P.; Kingsley, David H.
2011-01-01
The goal of this study was to determine how enteric viruses persist within shellfish tissues. Several lines of novel evidence show that phagocytic blood cells (hemocytes) of Eastern oysters (Crassostrea virginica) play an important role in the retention of virus particles. Our results demonstrated an association of virus contamination with hemocytes but not with hemolymph. Live oysters contaminated overnight with hepatitis A virus (HAV) and murine norovirus (MNV) had 56% and 80% of extractable virus associated with hemocytes, respectively. Transfer of HAV-contaminated hemocytes to naïve (virus-free) oysters resulted in naïve oyster meat testing HAV positive for up to 3 weeks. Acid tolerance of HAV, MNV, poliovirus (PV), and feline calicivirus (FCV) correlated with the ability of each virus to persist within oysters. Using reverse transcription-PCR (RT-PCR) to evaluate persistence of these viruses in oysters, we showed that HAV persisted the longest (>21 days) and was most acid resistant, MNV and PV were less tolerant of acidic pH, persisting for up to 12 days and 1 day, respectively, and FCV did not persist (<1 day) within oysters and was not acid tolerant. This suggests that the ability of a virus to tolerate the acidic conditions typical of phagolysosomal vesicles within hemocytes plays a role in determining virus persistence in shellfish. Evaluating oyster and hemocyte homogenates and live contaminated oysters as a prelude to developing improved viral RNA extraction methods, we found that viruses were extracted more expediently from hemocytes than from whole shellfish tissues and gave similar RT-PCR detection sensitivities. PMID:21948840
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Bento, Célia P M; Yang, Xiaomei; Gort, Gerrit; Xue, Sha; van Dam, Ruud; Zomer, Paul; Mol, Hans G J; Ritsema, Coen J; Geissen, Violette
2016-12-01
The dissipation kinetics of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) were studied in loess soil, under biotic and abiotic conditions, as affected by temperature, soil moisture (SM) and light/darkness. Nonsterile and sterile soil samples were spiked with 16mgkg -1 of glyphosate, subjected to three SM contents (20% WHC, 60% WHC, saturation), and incubated for 30days at 5°C and 30°C, under dark and light regimes. Glyphosate and AMPA dissipation kinetics were fit to single-first-order (SFO) or first-order-multicompartment (FOMC) models, per treatment combination. AMPA kinetic model included both the formation and decline phases. Glyphosate dissipation kinetics followed SFO at 5°C, but FOMC at 30°C. AMPA followed SFO dissipation kinetics for all treatments. Glyphosate and AMPA dissipation occurred mostly by microbial activity. Abiotic processes played a negligible role for both compounds. Under biotic conditions, glyphosate dissipation and AMPA formation/dissipation were primarily affected by temperature, but also by SM. Light regimes didn't play a significant role. Glyphosate DT50 varied between 1.5 and 53.5days, while its DT90 varied between 8.0 and 280days, depending on the treatment. AMPA persisted longer in soil than glyphosate, with its DT50 at 30°C ranging between 26.4 and 44.5days, and its DT90 between 87.8 and 148days. The shortest DT50/DT90 values for both compounds occurred at 30°C and under optimal/saturated moisture conditions, while the largest occurred at 5°C and reaching drought stress conditions. Based on these results, we conclude that glyphosate and AMPA dissipate rapidly under warm and rainy climate conditions. However, repeated glyphosate applications in fallows or winter crops in countries where cold and dry winters normally occur could lead to on-site soil pollution, with consequent potential risks to the environment and human health. To our knowledge, this study is the first evaluating the combined effect of temperature, soil moisture and light/dark conditions on AMPA formation/dissipation kinetics and behaviour. Copyright © 2016 Elsevier B.V. All rights reserved.
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Noar, Joe; Woods, Eva; Hodgson, Tim
2015-03-01
Whilst transient effects of orthodontic appliances on the oral mucosa are well recognized, chronic lesions, persisting post therapy are unusual. We describe a persistent lingual mucosal defect related to a transpalatal arch (TPA) in a healthy 19-year-old female. The asymptomatic lesion is presently being monitored, however, surgical revision in the future may be requested by the patient if the area fails to remodel. Clinical Relevance: Soft tissue trauma to the tongue by anchorage reinforcing appliances may result in long-term effects that could require surgical management.
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Goldoni, Matteo; Caglieri, Andrea; Poli, Diana; Vettori, Maria Vittoria; Corradi, Massimo; Apostoli, Pietro; Mutti, Antonio
2006-01-01
Chromium speciation has attracted attention because of the different toxicity of Cr(III), which is considered relatively non-toxic, and Cr(VI), which can cross cell membranes mainly as a chromate anion and has been classified as a class I human carcinogen. The aims of the present study were to measure soluble Cr(VI) levels in environmental samples, to develop a simple method of quantifying Cr(VI) in exhaled breath condensate (EBC), and to follow the kinetics of EBC Cr(VI) in chrome plating workers. Personal air samples were collected from 10 chrome platers; EBC was collected from the same workers immediately after the work shift on Tuesday and before the work shift on the following Wednesday. Environmental and EBC Cr(VI) levels were determined by means of colorimetry and electrothermal absorption atomic spectrometry, respectively. The method of detecting Cr(VI) in environmental air was based on the extraction of the Cr(VI)-diphenylcarbazide (Cr(VI)–DPC) complex in 1-butanol, whereas EBC Cr(VI) was determined using a solvent extraction of Cr(VI) as an ion pair with tetrabutylammonium ion, and subsequent direct determination of the complex (Cr(VI)–DPC) in EBC. Kinetic data showed that airborne Cr(VI) was reduced by 50% in airway lining fluid sampled at the end of exposure and that there was a further 50% reduction after about 15 h. The persistence of Cr(VI) in EBC supports the use of EBC in assessing target tissue levels of Cr(VI). PMID:17047732
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Zins, Stephen R; Amare, Mihret F; Tadaki, Douglas K; Elster, Eric A; Davis, Thomas A
2010-12-01
Impaired wound healing is a persistent clinical problem which has been treated with mixed results. Studies aimed at elucidating the mechanism of impaired wound healing have focused on small cohorts of genes which leave an incomplete picture of the wound healing process. We aimed to investigate impaired wound healing via a comprehensive panel of angiogenic/inflammation-related genes and wound closure kinetics with and without the application of extracorporeal shock wave therapy (ESWT), which has been demonstrated to improve wound healing. Full-thickness skin from the dorsal surface of "normal" (BALB/c) and "impaired" (db (+)/db (+)) mice was excised, and wound margin tissue was harvested 2, 7, and 10 days post injury. A separate, but identical wound model was established over 40 days in order to measure wound closure kinetics. Over time, the normal non-ESWT treated wounds exhibited varying patterns of elevated expression of 25-30 genes, whereas wounds with impaired healing displayed prolonged elevated expression of only a few genes (CXCL2, CXCL5, CSF3, MMP9, TGF-α). In response to ESWT, gene expression was augmented in both types of wounds, especially in the expression of PECAM-1; however, ESWT had no effect on wound closure in either model. In addition, multiple doses of ESWT exacerbated the delayed wound healing, and actually caused the wounds to initially increase in size. These data provide a more complete picture of impaired wound healing, and a way to evaluate various promising treatments.
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Herbicide residues in grapes and wine.
Ying, G G; Williams, B
1999-05-01
The persistence of several common herbicides from grapes to wine has been studied. Shiraz, Tarrango and Doradillo grapes were separately sprayed with either norflurazon, oxyfluorfen, oxadiazon or trifluralin-persistent herbicides commonly used for weed control in vineyards. The dissipation of the herbicides from the grapes was followed for 28 days following treatment. Results showed that norflurazon was the most persist herbicide although there were detectable residues of all the herbicides on both red and white grapes at the end of the study period. The penetration of herbicides into the flesh of the grapes was found to be significantly greater for white grapes than for red grapes. Small-lot winemaking experiments showed that norflurazon persisted at levels close to the initial concentration through vinification and into the finished wine. The other herbicides degraded, essentially via first-order kinetics, within the period of "first fermentation" and had largely disappeared after 28 days. The use of charcoal together with filter pads, or with diatomaceous earth was shown to be very effective in removing herbicide residues from the wine. A 5% charcoal filter removed more than 96% of the norflurazon persisting in the treated wine.
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von Holst, Hans; Li, Xiaogai
2013-07-01
Although the consequences of traumatic brain injury (TBI) and its treatment have been improved, there is still a substantial lack of understanding the mechanisms. Numerical simulation of the impact can throw further lights on site and mechanism of action. A finite element model of the human head and brain tissue was used to simulate TBI. The consequences of gradually increased kinetic energy transfer was analyzed by evaluating the impact intracranial pressure (ICP), strain level, and their potential influences on binding forces in folded protein structures. The gradually increased kinetic energy was found to have the potential to break apart bonds of Van der Waals in all impacts and hydrogen bonds at simulated impacts from 6 m/s and higher, thereby superseding the energy in folded protein structures. Further, impacts below 6 m/s showed none or very slight increase in impact ICP and strain levels, whereas impacts of 6 m/s or higher showed a gradual increase of the impact ICP and strain levels reaching over 1000 KPa and over 30%, respectively. The present simulation study shows that the free kinetic energy transfer, impact ICP, and strain levels all have the potential to initiate cytotoxic brain tissue edema by unfolding protein structures. The definition of mild, moderate, and severe TBI should thus be looked upon as the same condition and separated only by a gradual severity of impact.
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Leaching kinetics of As, Mo, and Se from acidic coal fly ash samples
DOE Office of Scientific and Technical Information (OSTI.GOV)
Neupane, Ghanashyam; Donahoe, Rona J.; Bhattacharyya, Siddhartha
Annually, coal-fired electric power plants produce large volumes potentially hazardous coal combustion products (CCPs) including fly ash. Since majority of the coal fly ash and other CCPs deposited in dry land fills or wet lagoons, they pose risk of contamination to local environment and hydrogeology. In this study, we present results of leaching kinetics for As, Mo, and Se from three acidic fly ash samples. This study shows that the leachate concentrations of As, Mo, and Se increase over time. Three kinetics equations, pseudo-second order, Elovich, and power-function, are able to adequately describe the experimental leaching kinetics data. Experimental leachingmore » data and modeling results indicate that the rate limiting leaching of As, Mo, and Se is largely controlled by the dissolution of the fly ash particles. Furthermore, it is important to adopt effective containment/treatment schemes to avoid potential and persistent dispersion of trace elements from ash disposal facilities to surrounding environment for a long time.« less
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Leaching kinetics of As, Mo, and Se from acidic coal fly ash samples
Neupane, Ghanashyam; Donahoe, Rona J.; Bhattacharyya, Siddhartha; ...
2017-07-03
Annually, coal-fired electric power plants produce large volumes potentially hazardous coal combustion products (CCPs) including fly ash. Since majority of the coal fly ash and other CCPs deposited in dry land fills or wet lagoons, they pose risk of contamination to local environment and hydrogeology. In this study, we present results of leaching kinetics for As, Mo, and Se from three acidic fly ash samples. This study shows that the leachate concentrations of As, Mo, and Se increase over time. Three kinetics equations, pseudo-second order, Elovich, and power-function, are able to adequately describe the experimental leaching kinetics data. Experimental leachingmore » data and modeling results indicate that the rate limiting leaching of As, Mo, and Se is largely controlled by the dissolution of the fly ash particles. Furthermore, it is important to adopt effective containment/treatment schemes to avoid potential and persistent dispersion of trace elements from ash disposal facilities to surrounding environment for a long time.« less
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Modified kinetics of enzymes interacting with nanoparticles
NASA Astrophysics Data System (ADS)
Díaz, Sebastián. A.; Breger, Joyce C.; Malanoski, Anthony; Claussen, Jonathan C.; Walper, Scott A.; Ancona, Mario G.; Brown, Carl W.; Stewart, Michael H.; Oh, Eunkeu; Susumu, Kimihiro; Medintz, Igor L.
2015-08-01
Enzymes are important players in multiple applications, be it bioremediation, biosynthesis, or as reporters. The business of catalysis and inhibition of enzymes is a multibillion dollar industry and understanding the kinetics of commercial enzymes can have a large impact on how these systems are optimized. Recent advances in nanotechnology have opened up the field of nanoparticle (NP) and enzyme conjugates and two principal architectures for NP conjugate systems have been developed. In the first example the enzyme is bound to the NP in a persistent manner, here we find that key factors such as directed enzyme conjugation allow for enhanced kinetics. Through controlled comparative experiments we begin to tease out specific mechanisms that may account for the enhancement. The second system is based on dynamic interactions of the enzymes with the NP. The enzyme substrate is bound to the NP and the enzyme is free in solution. Here again we find that there are many variables , such as substrate positioning and NP selection, that modify the kinetics.
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Maude, Shannon L.; Porter, David L.; Frey, Noelle; Wood, Patricia; Han, Xia; Waldron, Edward; Chakraborty, Abhijit; Awasthi, Rakesh; Levine, Bruce L.; Melenhorst, J. Joseph; Grupp, Stephan A.; June, Carl H.; Lacey, Simon F.
2017-01-01
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL). CTL019 was measured in peripheral blood and bone marrow, using quantitative polymerase chain reaction and flow cytometry. CTL019 levels in peripheral blood typically peaked at 10 to 14 days postinfusion and then declined slowly over time. Patients with complete response (CR)/CR with incomplete count recovery had higher levels of CTL019 in peripheral blood, with greater maximal concentration and area under the curve values compared with nonresponding patients (P < .0001 for each). CTL019 transgene levels were measurable up to 780 days in peripheral blood. CTL019 trafficking and persistence were observed in bone marrow and cerebrospinal fluid. CTL019 expansion correlated with severity of cytokine release syndrome (CRS) and preinfusion tumor burden in pediatric ALL. The results described here are the first detailed formal presentation of cellular kinetics across 2 diseases and highlight the importance of the application of in vivo cellular kinetic analyses to characterize clinical efficacy and CRS severity associated with CTL019 therapy. PMID:28935694
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Yu, Gang; Li, Shu-Hui; Cui, Meng-Xun; Yan, Ling-Di; Yong, Zheng; Zhou, Pei-Lan; Su, Rui-Bin; Gong, Ze-Hui
2014-03-01
It is considered that a long-acting therapy would be advantageous in the treatment of addiction. In a search for novel buprenorphine analogues, thienorphine was demonstrated to be an extremely long-acting orally active partial opioid agonist. This study explored the mechanisms underlying the long-lasting effects of thienorphine. The binding kinetics of [(3) H]thienorphine were measured in membrane preparations expressing cloned rat opioid receptors. Flow cytometric analysis was used to determine the effect of thienorphine on the surface opioid receptor number. The long-lasting effects of thienorphine were also confirmed at the tissue level and in vivo. At 37°C, [(3) H]thienorphine showed rapid association with μ- and κ-opioid receptors, while its dissociation was sluggish and biphasic (K-1 = 0.21 min(-1) , K-2 = 0.0078 min(-1) for the μ-receptor; K-1 = 0.17 min(-1) , K-2 = 0.0042 min(-1) for the κ-receptor). Treatment with thienorphine for 24, 48, and 72 h downregulated surface μ-receptor in a dose- and time-dependent manner. The inhibitory effect of thienorphine on guinea pig ileum persisted for more than 120 min after prolonged washing. In vivo, thienorphine exhibited significant antagonism of morphine-induced antinociception for more than 7 days. These results indicate that multiple factors, including persistent receptor occupation and enhanced receptor downregulation, may contribute to the long-lasting effects of thienorphine that would be beneficial for its application in addiction treatment. © 2013 John Wiley & Sons Ltd.
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Pfaller, Kristian; Wagner, Johanna
2016-01-01
Extracellular ice nucleation usually occurs at mild subzero temperatures in most plants. For persistent supercooling of certain plant parts ice barriers are necessary to prevent the entry of ice from already frozen tissues. The reproductive shoot of Calluna vulgaris is able to supercool down to below -22°C throughout all developmental stages (shoot elongation, flowering, fruiting) despite an established xylem conductivity. After localization of the persistent ice barrier between the reproductive and vegetative shoot at the base of the pedicel by infrared differential thermal analysis, the currently unknown structural features of the ice barrier tissue were anatomically analyzed on cross and longitudinal sections. The ice barrier tissue was recognized as a 250 μm long constriction zone at the base of the pedicel that lacked pith tissue and intercellular spaces. Most cell walls in this region were thickened and contained hydrophobic substances (lignin, suberin, and cutin). A few cell walls had what appeared to be thicker cellulose inclusions. In the ice barrier tissue, the area of the xylem was as much as 5.7 times smaller than in vegetative shoots and consisted of tracheids only. The mean number of conducting units in the xylem per cross section was reduced to 3.5% of that in vegetative shoots. Diameter of conducting units and tracheid length were 70% and 60% (respectively) of that in vegetative shoots. From vegetative shoots water transport into the ice barrier must pass pit membranes that are likely impermeable to ice. Pit apertures were about 1.9 μm x 0.7 μm, which was significantly smaller than in the vegetative shoot. The peculiar anatomical features of the xylem at the base of the pedicel suggest that the diameter of pores in pit membranes could be the critical constriction for ice propagation into the persistently supercooled reproductive shoots of C. vulgaris. PMID:27632365
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Kuprian, Edith; Tuong, Tan D; Pfaller, Kristian; Wagner, Johanna; Livingston, David P; Neuner, Gilbert
2016-01-01
Extracellular ice nucleation usually occurs at mild subzero temperatures in most plants. For persistent supercooling of certain plant parts ice barriers are necessary to prevent the entry of ice from already frozen tissues. The reproductive shoot of Calluna vulgaris is able to supercool down to below -22°C throughout all developmental stages (shoot elongation, flowering, fruiting) despite an established xylem conductivity. After localization of the persistent ice barrier between the reproductive and vegetative shoot at the base of the pedicel by infrared differential thermal analysis, the currently unknown structural features of the ice barrier tissue were anatomically analyzed on cross and longitudinal sections. The ice barrier tissue was recognized as a 250 μm long constriction zone at the base of the pedicel that lacked pith tissue and intercellular spaces. Most cell walls in this region were thickened and contained hydrophobic substances (lignin, suberin, and cutin). A few cell walls had what appeared to be thicker cellulose inclusions. In the ice barrier tissue, the area of the xylem was as much as 5.7 times smaller than in vegetative shoots and consisted of tracheids only. The mean number of conducting units in the xylem per cross section was reduced to 3.5% of that in vegetative shoots. Diameter of conducting units and tracheid length were 70% and 60% (respectively) of that in vegetative shoots. From vegetative shoots water transport into the ice barrier must pass pit membranes that are likely impermeable to ice. Pit apertures were about 1.9 μm x 0.7 μm, which was significantly smaller than in the vegetative shoot. The peculiar anatomical features of the xylem at the base of the pedicel suggest that the diameter of pores in pit membranes could be the critical constriction for ice propagation into the persistently supercooled reproductive shoots of C. vulgaris.
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Experimental Model for the Study of Periodontal Wound Healing
1991-05-01
the soft tissue over the submerged root may occur. Models that communicate with the oral cavity (i.e., experimentally produced and naturally...membranes have been successfully utilized to demonstrate regeneration of periodontal tissues . Membranes made of collagen (Pitaru etal., 1987, 1988 a & b...1988. Progenitor cell kinetics during guided tissue regeneration in experimental periodontal wounds. J Periodont Res 23:107. Isidor, F., Karring, T
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Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats.
Pujalté, Igor; Dieme, Denis; Haddad, Sami; Serventi, Alessandra Maria; Bouchard, Michèle
2017-01-04
This study focused on the generation of aerosols of titanium dioxide (TiO 2 ) nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley rats were exposed by inhalation to 15mg/m 3 of anatase TiO 2 NPs (∼20nm) during 6h. Rats were sacrificed at different time points over 14days following the onset of inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta. Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were found in lungs; peak values were reached only at 48h followed by a progressive decrease over 14days, suggesting a persistence of NPs at the site-of-entry. Levels reached in blood, lymph nodes and other internal organs (including liver, kidney, spleen) were circa one order of magnitude lower than in lungs, but the profiles were indicative of a certain translocation to the systemic circulation. Large amounts were recovered in feces compared to urine, suggesting that inhaled NPs were eliminated mainly by mucociliary clearance and ingested. TiO 2 NPs also appeared to be partly transferred to olfactory bulbs and brain. MDA levels indicative of oxidative damage were significantly increased in lungs and blood at 24h but this was not clearly reflected at later times. Translocation and clearance rates of inhaled NPs under different realistic exposure conditions should be further documented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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AUV and Aircraft Measurements of an Internal Hydraulic Jump at the Mouth of the Columbia River
NASA Astrophysics Data System (ADS)
McNeil, C. L.
2016-02-01
In 2013, an extensive 3-km long persistent hydraulic jump in the Mouth of the Columbia River (MCR) was captured in a joint pilot study involving coordinated autonomous and remote sensing observations. Airborne thermal infrared (IR) cameras provided observations of surface brightness temperature, while an along-track interferometric synthetic aperture radar (ATI-SAR) measured surface velocity and roughness. Subsurface hydrographic surveys were conducted with a REMUS autonomous underwater vehicle (AUV). These observations showed a flow- oblique stationary front that persisted through most of an ebb-tide. A pronounced dip and divergence (mixing) of the isohaline surfaces downstream of the surface front suggested that the newly-discovered feature is an internal hydraulic jump. Hydraulic jumps reduce kinetic energy of a laminar flow, partially converting it to turbulent kinetic energy that, in turn, increases the potential energy of the system via mixing. Our goal is to quantify this mixing associated with the MCR jump using our existing data, and more generally assess the jump's impact on the physics and biology of the lower estuary, plume, and coastal ocean.
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Rapid wall relaxation in elongating tissues.
Matyssek, R; Maruyama, S; Boyer, J S
1988-04-01
Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision.
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Rapid Wall Relaxation in Elongating Tissues 1
Matyssek, Rainer; Maruyama, Sachio; Boyer, John S.
1988-01-01
Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision. PMID:16666048
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Makeev, Alexei G; Kurkina, Elena S; Kevrekidis, Ioannis G
2012-06-01
Kinetic Monte Carlo simulations are used to study the stochastic two-species Lotka-Volterra model on a square lattice. For certain values of the model parameters, the system constitutes an excitable medium: travelling pulses and rotating spiral waves can be excited. Stable solitary pulses travel with constant (modulo stochastic fluctuations) shape and speed along a periodic lattice. The spiral waves observed persist sometimes for hundreds of rotations, but they are ultimately unstable and break-up (because of fluctuations and interactions between neighboring fronts) giving rise to complex dynamic behavior in which numerous small spiral waves rotate and interact with each other. It is interesting that travelling pulses and spiral waves can be exhibited by the model even for completely immobile species, due to the non-local reaction kinetics.
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USDA-ARS?s Scientific Manuscript database
Extracellular ice nucleation usually occurs at mild subzero temperatures in most plants. For persistent supercooling of certain plant parts ice barriers are necessary that prevent the entry of ice from otherwise already frozen tissues. The reproductive shoot of the evergreen woody dwarf shrub Callun...
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Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.
Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan
2017-10-01
Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.
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Mapp, Tiffany; Mama, Saifuddin; Echols, Karolynn T.
2012-01-01
Introduction: There have been many reports in the literature on vaginal mesh erosion as a complication of pelvic floor reconstructive surgery. Several reports describe successful surgical excision of the exposed mesh as a resolution. However, in rare cases of mesh erosion, poor surgical outcomes and multiple resection failures have been reported. We describe an innovative surgical approach to persistent vaginal mesh erosion using CO2 laser vaporization under colposcopic and laparoscopic guidance. Case Description: A 58-y-old postmenopausal woman first presented with a 3-y history of vaginal discharge and spotting after undergoing a Mentor ObTape transobturator sling (Mentor Corp, Santa Barbara, CA), for the treatment of stress urinary incontinence. Despite surgical removal of the mesh and multiple attempts at cauterization of persistent granulation tissue, her symptoms persisted. Discussion: Using a CO2 laser under colposcopic and laparoscopic guidance, we were able to safely expose and remove the remaining portion of retained mesh. To our knowledge, this is the first report describing CO2 laser vaporization as a surgical approach for the successful treatment of recurrent mesh erosion. PMID:23318081
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Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
Morales-Nebreda, Luisa; Cuda, Carla M.; Walter, James M.; Chen, Ching-I; Anekalla, Kishore R.; Joshi, Nikita; Williams, Kinola J.N.; Abdala-Valencia, Hiam; Yacoub, Tyrone J.; Chi, Monica; Gates, Khalilah; Homan, Philip J.; Soberanes, Saul; Dominguez, Salina; Saber, Rana; Hinchcliff, Monique; Marshall, Stacy A.; Bharat, Ankit; Berdnikovs, Sergejs; Bhorade, Sangeeta M.; Balch, William E.; Chandel, Navdeep S.; Jain, Manu; Ridge, Karen M.; Bagheri, Neda; Shilatifard, Ali
2017-01-01
Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion. PMID:28694385
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Persistent measles virus infection of the intestine: confirmation by immunogold electron microscopy.
Lewin, J; Dhillon, A P; Sim, R; Mazure, G; Pounder, R E; Wakefield, A J
1995-01-01
This study sought to investigate persistent measles virus infection of the intestine: a novel protocol for immunogold electron microscopy was developed using a polyclonal anti-measles nucleoprotein antibody on reprocessed, formalin fixed paraffin wax embedded tissue sections. Antibody binding was detected using both immunoperoxidase and light microscopy on tissue sections, and 10 nm gold conjugated secondary antibody and electron microscopy on ultrathin sections. The techniques were validated using both measles infected vero cells and human tissues with established measles infection: these included brain affected by subacute sclerosing panencephalitis and acute measles appendicitis. The technique was applied subsequently to six untreated cases of granulomatous Crohn's disease, and two cases of ileocaecal tuberculosis, a granulomatous control. Mumps primary antibody--applied to both mumps infected vero cells, and measles infected vero cells and tissues studied by immunoperoxidase, and measles antibody on mumps infected cells studied by immunoperoxidase and immunogold--were used as specificity controls: the primary antibodies identified their respective target antigen and there was no antibody cross reactivity. Measles virus nucleocapsids labelled with gold conjugated antibody in both infected cells and tissues, including foci of granulomatous inflammation in five of six cases of Crohn's disease: in the fifth case, the granuloma could not be identified in ultrathin section. In one of the tuberculosis cases, a low level of signal was noted while the second case was negative. Labelling adopted a characteristic pattern in all infected tissues, strengthening the specificity of these findings. This study provides the first direct confirmation of persistent measles virus infection of the intestine. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7737565
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Tissue-specific and time-dependent clonal expansion of ENU-induced mutant cells in gpt delta mice.
Nakayama, Takafumi; Sawai, Tomoko; Masuda, Ikuko; Kaneko, Shinya; Yamauchi, Kazumi; Blyth, Benjamin J; Shimada, Yoshiya; Tachibana, Akira; Kakinuma, Shizuko
2017-10-01
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment. The gpt mutations were passengers of the mutant cell of origin and its daughter cells and thus could be used as neutral markers of clones that arose and persisted in the tissues. Female B6C3F1 mice exposed for 1 month to 200 ppm ENU in the drinking water developed early thymic lymphomas and late liver and lung tumors. To assay gpt mutations, we sampled the thymus, liver, lung, and small intestine of female gpt delta mice at 3 days, 4 weeks, and 8 weeks after the end of ENU exposure. Our results reveal that, in all four tissues, the ENU-induced gpt mutations persisted for weeks after the end of mutagen exposure. Clonal expansion of mutant cells was observed in the thymus and small intestine, with the thymus showing larger clone sizes. These results indicate that the clearance of mutant cells and the potential for clonal expansion during normal tissue growth depends on tissue type and that these factors may affect the sensitivity of different tissues to carcinogenesis. Environ. Mol. Mutagen. 58:592-606, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Degradation and persistence of cotton pesticides in sandy loam soils from Punjab, Pakistan.
Tariq, Muhammad Ilyas; Afzal, Shahzad; Hussain, Ishtiaq
2006-02-01
The present study evaluated the influence of temperature, moisture, and microbial activity on the degradation and persistence of commonly used cotton pesticides, i.e., carbosulfan, carbofuran, lambda-cyhalothrin, endosulfan, and monocrotophos, with the help of laboratory incubation and lysimeter studies on sandy loam soil (Typic Ustocurepts) in Pakistan. Drainage from the lysimeters was sampled on days 49, 52, 59, 73, 100, 113, and 119 against the pesticide application on days 37, 63, 82, 108, and 137 after the sowing of cotton. Carbofuran, monocrotophos, and nitrate were detected in the drainage samples, with an average value, respectively, of 2.34, 2.6 microg/L, and 15.6 mg/L for no-tillage and 2.16, 2.3 microg/L, and 13.4 mg/L for tillage. In the laboratory, pesticide disappearance kinetics were measured with sterile and nonsterile soils from 0 to 10 cm in depth at 15, 25, and 35 degrees C and 50% and 90% field water capacities. Monocrotophos and carbosulfan dissipation followed first-order kinetics while others followed second-order kinetics. The results of incubation studies showed that temperature and moisture contents significantly reduced the t(1/2) (half-life) values of pesticides in sterile and nonsterile soil, but the effect of microbial activity was nearly significant that might be due to less organic carbon (0.3%). The presence of carbofuran and monocrotophos in the soil profile (0-10, 10-30, 30-60, 60-90, 90-150 cm) and the higher concentrations of endosulfan and lambda-cyhalothrin in the top layer (0-10 cm) showed the persistence of the pesticides. The detection of endosulfan and lambda-cyhalothrin in the 10-30 cm soil layer might be due to preferential flow. The data generated from this study could be helpful for risk assessment studies of pesticides and for validating pesticide transport models for sandy loam soils in cotton-growing areas of Pakistan.
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Role of Kinetic Modeling in Biomedical Imaging
Huang, Sung-Cheng
2009-01-01
Biomedical imaging can reveal clear 3-dimensional body morphology non-invasively with high spatial resolution. Its efficacy, in both clinical and pre-clinical settings, is enhanced with its capability to provide in vivo functional/biological information in tissue. The role of kinetic modeling in providing biological/functional information in biomedical imaging is described. General characteristics and limitations in extracting biological information are addressed and practical approaches to solve the problems are discussed and illustrated with examples. Some future challenges and opportunities for kinetic modeling to expand the capability of biomedical imaging are also presented. PMID:20640185
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Kinetics of natural oxidant demand by permanganate in aquifer solids.
Urynowicz, Michael A; Balu, Balamurali; Udayasankar, Umamaheshwari
2008-02-19
During in situ chemical oxidation with permanganate, natural organic matter and other reduced species in the subsurface compete with the target compounds for the available oxidant and can exert a significant natural oxidant demand. This competition between target and nontarget compounds can have a significant impact on the permeation, dispersal, and persistence of permanganate in the subsurface. The kinetics of natural oxidant demand by permanganate was investigated using a composite sample made up of aquifer material collected from three different sites. The study found that although the depletion of organic carbon increased with increased permanganate dosage and increased reaction period, the mass ratio of MnO(4)(-):OC (wt/wt) was relatively constant over time (11.4+/-0.9). The reaction order and rate with respect to permanganate were found to decrease with time suggesting a continuum of reactions with the slower reactions becoming more controlling with time. However, the data also suggests that this continuum of reactions can be simplified into short- and long-term kinetic expressions representing fast and slow reactions. An independent first-order kinetic model with separate fast and slow reaction rate constants was used to successfully describe the complete kinetic expression of natural oxidant demand. The kinetic parameters used in the model are easily determined and can be used to better understand the complex kinetics of natural oxidant demand.
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Song, Xiaokai; Zhang, Zeyang; Liu, Chang; Xu, Lixin; Yan, Ruofeng; Li, Xiangrui
2016-10-15
In a previous study, the construction of the Eimeria tenella DNA vaccine pVAX1.0-TA4-IL-2 which provides effective protection against coccidiosis was described and the immunization procedure was optimized. However, the persistence, integration, histopathology and environmental release of the DNA vaccine remain unknown. In this study, the persistence, integration and histopathology of the DNA vaccine pVAX1.0-TA4-IL-2 was evaluated in chickens in the following immunization studies: (1) single-dose immunization in one-day-old chickens; (2) repeat-dose immunization in chickens; and (3) single-high-dose immunization of three batches of plasmid in chickens. The persistence, integration, histopathology of the DNA vaccine was also evaluated in mice. At 1, 1.5, 2-4 months post immunization, blood, duodenum, heart, liver, spleen, kidneys and the immunized muscle tissue were collected from ten animals of each group. Persistence and integration were evaluated using PCR with a confirmed sensitivity of 30 plasmid copies. Hematoxylin and eosin stained sections were examined for the presence of inflammation or abnormalities that may result from vaccination. Water and fecal samples were also collected from the chicken enclosures to evaluate the potential for environmental release of the DNA vaccine. Testing various tissues by PCR confirmed that plasmid DNA persisted 1.5 months in blood, heart, liver and spleen, 2 months in kidneys and muscle of injected site. Furthermore, the vaccine did not integrate with the host genome. The histopathological examinations did not show obvious inflammation or pathological damage in any tissue of the immunized chickens. Similar results were observed in mice. Moreover, the DNA vaccine was not released into the surrounding environment. These results indicate that the DNA vaccine pVAX1.0-TA4-IL-2 has potential as safe vaccine against coccidiosis. Copyright © 2016 Elsevier B.V. All rights reserved.
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Synchronous Oscillations in Microtubule Polymerization
NASA Astrophysics Data System (ADS)
Carlier, M. F.; Melki, R.; Pantaloni, D.; Hill, T. L.; Chen, Y.
1987-08-01
Under conditions where microtubule nucleation and growth are fast (i.e., high magnesium ion and tubulin concentrations and absence of glycerol), microtubule assembly in vitro exhibits an oscillatory regime preceding the establishment of steady state. The amplitude of the oscillations can represent >50% of the maximum turbidity change and oscillations persist for up to 20 periods of 80 s each. Oscillations are accompanied by extensive length redistribution of microtubules. Preliminary work suggests that the oscillatory kinetics can be simulated using a model in which many microtubules undergo synchronous transitions between growing and rapidly depolymerizing phases, complicated by the kinetically limiting rate of nucleotide exchange on free tubulin.
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Contaminants in fish tissue from US lakes and reservoirs: A national probabilistic study
An unequal probability design was used to develop national estimates for 268 persistent, bioaccumulative, and toxic chemicals in fish tissue from lakes and reservoirs of the conterminous United States (excluding the Laurentian Great Lakes and Great Salt Lake). Predator (fillet) ...
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Eradication of HIV from Tissue Reservoirs: Challenges for the Cure.
Rose, Rebecca; Nolan, David J; Maidji, Ekaterina; Stoddart, Cheryl A; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S
2018-01-01
The persistence of HIV infection, even after lengthy and successful combined antiretroviral therapy (cART), has precluded an effective cure. The anatomical locations and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. In this study, we review research supporting the importance of anatomical tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages. We present accumulated research that clearly demonstrates the limitations of using blood-derived cells as a proxy for tissue reservoirs and sanctuaries throughout the body. We cite recent studies that have successfully used deep-sequencing strategies to uncover the complexity of HIV infection and the ability of the virus to evolve despite undetectable plasma viral loads. Finally, we suggest new strategies and highlight the importance of tissue banks for future research.
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Sakala, Isaac G; Chaudhri, Geeta; Scalzo, Anthony A; Eldi, Preethi; Newsome, Timothy P; Buller, Robert M; Karupiah, Gunasegaran
2015-12-01
Orthopoxviruses (OPV), including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV), the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. We used the mouse pathogen ectromelia virus (ECTV), the agent of mousepox and a close relative of VARV to investigate virus persistence in inbred mice. We provide evidence that ECTV causes a persistent infection in some susceptible strains of mice in which low levels of virus genomes were detected in various tissues late in infection. The bone marrow (BM) and blood appeared to be key sites of persistence. Contemporaneous with virus persistence, antiviral CD8 T cell responses were demonstrable over the entire 25-week study period, with a change in the immunodominance hierarchy evident during the first 3 weeks. Some virus-encoded host response modifiers were found to modulate virus persistence whereas host genes encoded by the NKC and MHC class I reduced the potential for persistence. When susceptible strains of mice that had apparently recovered from infection were subjected to sustained immunosuppression with cyclophosphamide (CTX), animals succumbed to mousepox with high titers of infectious virus in various organs. CTX treated index mice transmitted virus to, and caused disease in, co-housed naïve mice. The most surprising but significant finding was that immunosuppression of disease-resistant C57BL/6 mice several weeks after recovery from primary infection generated high titers of virus in multiple tissues. Resistant mice showed no evidence of a persistent infection. This is the strongest evidence that ECTV can persist in inbred mice, regardless of their resistance status.
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Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Juleff, Nicholas
2016-01-01
ABSTRACT Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem. PMID:26962214
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Persistence of external signs in Pacific herring Clupea pallasii Valenciennes with ichthyophoniasis
Hart, Lucas M.; Conway, Carla M.; Elliott, Diane G.; Hershberger, Paul K.
2016-01-01
The progression of external signs of Ichthyophonus infection in Pacific herring Clupea pallasii Valenciennes was highly variable and asynchronous after intraperitoneal injection with pure parasite preparations; however, external signs generally persisted through the end of the study (429 days post-exposure). Observed signs included papules, erosions and ulcers. The prevalence of external signs plateaued 35 days post-exposure and persisted in 73–79% of exposed individuals through the end of the first experiment (147 days post-exposure). Among a second group of infected herring, external signs completely resolved in only 10% of the fish after 429 days. The onset of mortality preceded the appearance of external signs. Histological examination of infected skin and skeletal muscle tissues indicated an apparent affinity of the parasite for host red muscle. Host responses consisted primarily of granulomatous inflammation, fibrosis and necrosis in the skeletal muscle and other tissues. The persistence and asynchrony of external signs and host response indicated that they were neither a precursor to host mortality nor did they provide reliable metrics for hindcasting on the date of exposure. However, the long-term persistence of clinical signs in Pacific herring may be useful in ascertaining the population-level impacts of ichthyophoniasis in regularly observed populations.
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Kuppusamy, P; Chzhan, M; Vij, K; Shteynbuk, M; Lefer, D J; Giannella, E; Zweier, J L
1994-01-01
It has been hypothesized that free radical metabolism and oxygenation in living organs and tissues such as the heart may vary over the spatially defined tissue structure. In an effort to study these spatially defined differences, we have developed electron paramagnetic resonance imaging instrumentation enabling the performance of three-dimensional spectral-spatial images of free radicals infused into the heart and large vessels. Using this instrumentation, high-quality three-dimensional spectral-spatial images of isolated perfused rat hearts and rabbit aortas are obtained. In the isolated aorta, it is shown that spatially and spectrally accurate images of the vessel lumen and wall could be obtained in this living vascular tissue. In the isolated rat heart, imaging experiments were performed to determine the kinetics of radical clearance at different spatial locations within the heart during myocardial ischemia. The kinetic data show the existence of regional and transmural differences in myocardial free radical clearance. It is further demonstrated that EPR imaging can be used to noninvasively measure spatially localized oxygen concentrations in the heart. Thus, the technique of spectral-spatial EPR imaging is shown to be a powerful tool in providing spatial information regarding the free radical distribution, metabolism, and tissue oxygenation in living biological organs and tissues. Images PMID:8159757
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Peterson, Christopher W.; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Holmes, Michael C.; Estes, Jacob D.
2018-01-01
Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents. PMID:29672640
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Hodzic, Emir
2015-01-01
The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes. PMID:26295288
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Hodzic, Emir
2015-07-08
The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present: in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes.
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Parametric mapping of [18F]fluoromisonidazole positron emission tomography using basis functions.
Hong, Young T; Beech, John S; Smith, Rob; Baron, Jean-Claude; Fryer, Tim D
2011-02-01
In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K(1), k(2), k(3), K(i)) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [(18)F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. K(i) determined from BAFPIC has lower variability than that from the Patlak-Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k(3) maps is aided by low variability in normoxic tissue, which matches that in K(i) maps. BAFPIC produces K(i) values that correlate well with those from PGA (r(2)=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance.
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Tao, Xinrong; Garron, Tania; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Peng, Bi-Hung; Wakamiya, Maki; Chan, Teh-Sheng; Lu, Lu; Du, Lanying; Jiang, Shibo; Couch, Robert B; Tseng, Chien-Te K
2016-01-01
Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings
NASA Technical Reports Server (NTRS)
Epel, B. L.; Bandurski, R. S.
1990-01-01
Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.
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Zhu, Li; Hwang, Peter; Witkowska, H. Ewa; Liu, Haichuan; Li, Wu
2014-01-01
Tooth enamel is the hardest tissue in vertebrate animals. Consisting of millions of carbonated hydroxyapatite crystals, this highly mineralized tissue develops from a protein matrix in which amelogenin is the predominant component. The enamel matrix proteins are eventually and completely degraded and removed by proteinases to form mineral-enriched tooth enamel. Identification of the apatite-binding motifs in amelogenin is critical for understanding the amelogenin–crystal interactions and amelogenin–proteinases interactions during tooth enamel biomineralization. A stepwise strategy is introduced to kinetically and quantitatively identify the crystal-binding motifs in amelogenin, including a peptide screening assay, a competitive adsorption assay, and a kinetic-binding assay using amelogenin and gene-engineered amelogenin mutants. A modified enzyme-linked immunosorbent assay on crystal surfaces is also applied to compare binding amounts of amelogenin and its mutants on different planes of apatite crystals. We describe the detailed protocols for these assays and provide the considerations for these experiments in this chapter. PMID:24188774
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Smędra-Kaźmirska, Anna; Barzdo, Maciej; Kędzierski, Maciej; Antoszczyk, Łukasz; Szram, Stefan; Berent, Jarosław
2013-09-01
Pursuant to the Polish Weapons and Ammunitions Law (Legal Gazette No 53/1999 item 549 with subsequent amendments), air guns with kinetic energy of the fired projectiles below 17 J are not regarded as weapons. The aim of the study was to assess the potential effect of shots caused by projectiles of various mass and structure fired from air guns with kinetic energy below 17 J on human soft tissues. As a model of soft tissue, we used 20% gelatin blocks. After shooting, we measured the depth of gelatin block penetration by pellets fired from various distances and compared these results with autopsy findings. The results demonstrated that examined pneumatic guns may cause serious injuries, including damage to the pleura, pericardium, liver, spleen, kidneys, femoral artery, and thoracic and abdominal aorta. Experiment shown that gelatin blocks do not reflect fully the properties of the human body. © 2013 American Academy of Forensic Sciences.
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U.S. EPA conducted a national statistical survey of fish tissue contamination at 540 river sites (representing 82 954 river km) in 2008–2009, and analyzed samples for 50 persistent organic pollutants (POPs), including 21 PCB congeners, 8 PBDE congeners, and 21 organoc...
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Kurlaev, P P; Chernova, O L; Kirgizova, S B
2000-01-01
The suppressive action of oxytocin, heliumneon radiation and ultrahigh-frequency electromagnetic waves (UHF-therapy) on the persistence properties of S. aureus has been experimentally established. The effectiveness of the therapeutic actions under study in the treatment of patients with the prognosticated unfavorable course of purulent inflammatory diseases of soft tissues has been shown.
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USDA-ARS?s Scientific Manuscript database
Aim. Bovine viral diarrhea viruses (BVDV) are economically important pathogens of cattle. Most new acute infections of BVDV are acquired from an animal persistently infected (PI) with BVDV. Surveillance programs typically rely on blood or skin biopsies for detection of PI cattle. PI animals have ...
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Kinetic Modeling of PET Data Without Blood Sampling
NASA Astrophysics Data System (ADS)
Bentourkia, M.
2005-06-01
In positron emission tomography (PET) imaging, application of kinetic modeling always requires an input curve (IC) together with the PET data. The IC can be obtained by means of external blood sampling or, in the case of cardiac studies, by means of a region-of-interest (ROI) drawn on the blood pool. It is, however, very unsuitable to withdraw and to analyze blood samples, and in small animals, these operations become difficult, while ICs determined from ROIs are generally contaminated by emissions from neighboring sites, or they are underestimated because of partial volume effect. In this paper, we report a new method to extract kinetic parameters from dynamic PET studies without a priori knowledge of the IC. The method is applied in human brain data measured with fluorodeoxyglucose (FDG) human-brain and in cardiac-rat perfusion studies with /sup 13/N-ammonia and /sup 11/C-acetate. The tissue blood volume (TBV), usually fitted together with the rate constants, is extracted simultaneously with the tissue time activity curves for cardiac studies, while for brain gray matter, TBV is known to be about 4% to 7%. The shape of IC is obtained by means of factor analysis from an ROI drawn around a cardiac tissue or a brain artery. The results show a good correlation (p<0.05) between the cerebral metabolic rate of glucose, myocardial blood flow, and oxygen consumption obtained with the new method in comparison to the usual method. In conclusion, it is possible to apply kinetic modeling without any blood sampling, which significantly simplifies PET acquisition and data analysis.
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NASA Astrophysics Data System (ADS)
Pellerin, Morgane; Castaing, Victor; Gourier, Didier; Chanéac, Corinne; Viana, Bruno
2018-02-01
Persistent luminescence materials present many applications including security lighting and bio-imaging. Many progresses have been made in the elaboration of persistent luminescent nanoparticles suitable for the first NIR partial transparency window (650 - 950 nm). Moving to the second and third near-infrared partial transparency windows (1000 nm - 1800 nm) allows further reducing of scattering, absorption and tissue autofluorescence effects. In this work, we present the synthesis of Co2+ and Ni2+ doped zinc-gallate nanoparticles with broad emission covering the NIR-II range. Site occupancy, energy levels, optical features and persistent phenomena are presented.
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Absorption and distribution kinetics of the 13C-labeled tomato carotenoid phytoene in healthy adults
USDA-ARS?s Scientific Manuscript database
Phytoene is a tomato carotenoid which may contribute to the apparent health benefits of tomato consumption. While phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lyc...
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Plasmid-dependent attachment of Agrobacterium tumefaciens to plant tissue culture cells.
Matthysse, A G; Wyman, P M; Holmes, K V
1978-01-01
Kinetic, microscopic, and biochemical studies show that virulent Ti (tumor inducing)-plasmid-containing strains of Agrobacterium attach to normal tobacco and carrot tissue culture cells. Kinetic studies showed that virulent strains of A. tumefaciens attach to the plant tissue culture cells in increasing numbers during the first 1 to 2 h of incubation of the bacteria with the plant cells. Five Ti-plasmid-containing virulent Agrobacterium strains showed greater attachment to tobacco cells than did five avirulent strains. Light and scanning electron microscopic observations confirmed that virulent strains showed little attachment. Bacterial attachment was blocked by prior incubation of the plant cells with lipopolysaccharide extracted from A. tumefaciens, but not from A. radiobacter, suggesting that bacterial lipopolysaccharide is one of the components involved in the attachment process. At least one other bacterial product may be required for attachment in tissue culture because the virulent A. tumefaciens NT1, which lacks the Ti plasmid, does not itself attach to tobacco cells, but its lipopolysaccharide does inhibit the attachment of virulent strains. Images PMID:730370
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Energy transfer and kinetics in mechanochemistry.
Chen, Zhiliang; Lu, Shengyong; Mao, Qiongjing; Buekens, Alfons; Wang, Yuting; Yan, Jianhua
2017-11-01
Mechanochemistry (MC) exerts extraordinary degradation and decomposition effects on many chlorinated, brominated, and even fluorinated persistent organic pollutants (POPs). However, its application is still limited by inadequate study of its reaction kinetic aspects. In the present work, the ball motion and energy transfer in planetary ball mill are investigated in some detail. Almost all milling parameters are summarised in a single factor-total effective impact energy. Furthermore, the MC kinetic between calcium oxide/Al and hexachlorobenzene is well established and modelled. The results indicate that total effective impact energy and reagent ratio are the two factors sufficient for describing the MC degradation degree of POPs. The reaction rate constant only depends on the chemical properties of reactants, so it could be used as an important index to appraise the quality of MC additives. This model successfully predicts the reaction rate for different operating conditions, indicating that it could be suitably applied for conducting MC reactions in other reactors.
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Numerical models of laser fusion of intestinal tissues.
Pearce, John A
2009-01-01
Numerical models of continuous wave Tm:YAG thermal fusion in rat intestinal tissues were compared to experiment. Optical and thermal FDM models that included tissue damage based on Arrhenius kinetics were used to predict birefringence loss in collagen as the standard of comparison. The models also predicted collagen shrinkage, jellification and water loss. The inclusion of variable optical and thermal properties is essential to achieve favorable agreement between predicted and measured damage boundaries.
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Survey design for lakes and reservoirs in the United States to assess contaminants in fish tissue
The National Lake Fish Tissue Study (NLFTS) was the first survey of fish contamination in lakes and reservoirs in the 48 conterminous states based on probability survey design. This study included the largest set (268) of persistent, bioaccumulative, and toxic (PBT) chemicals ev...
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Fish early life stages are highly sensitive to exposure to persistent bioaccumulative toxicants (PBTs). The factors that contribute to this are unknown, but may include the distribution of PBTs to sensitive tissues during critical stages of development. Multiphoton laser scannin...
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Vegetation effects on soil organic matter chemistry of aggregate fractions in a Hawaiian forest
USDA-ARS?s Scientific Manuscript database
We examined chemical changes from live plant tissue to soil organic matter (SOM) to determine the persistence of individual plant compounds into soil aggregate fractions. We characterized the tissue chemistry of a slow- (Dicranopteris linearis) and fast-decomposing species (Cheirodendron trigynum) a...
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Generation of radicals in hard biological tissues under the action of laser radiation
NASA Astrophysics Data System (ADS)
Sviridov, Alexander P.; Bagratashvili, Victor N.; Sobol, Emil N.; Omelchenko, Alexander I.; Lunina, Elena V.; Zhitnev, Yurii N.; Markaryan, Galina L.; Lunin, Valerii V.
2002-07-01
The formation of radicals upon UV and IR laser irradiation of some biological tissues and their components was studied by the EPR technique. The radical decay kinetics in body tissue specimens after their irradiation with UV light were described by various models. By the spin trapping technique, it was shown that radicals were not produced during IR laser irradiation of cartilaginous tissue. A change in optical absorption spectra and the dynamics of optical density of cartilaginous tissue, fish scale, and a collagen film under exposure to laser radiation in an air, oxygen, and nitrogen atmosphere was studied.
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Development of a platform for co-registered ultrasound and MR contrast imaging in vivo
NASA Astrophysics Data System (ADS)
Chandrana, Chaitanya; Bevan, Peter; Hudson, John; Pang, Ian; Burns, Peter; Plewes, Donald; Chopra, Rajiv
2011-02-01
Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.
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Sörensen, Jens; Owenius, Rikard; Lax, Michelle; Johansson, Silvia
2013-02-01
[(18)F]Fluciclovine (anti-[(18)F]FACBC) is a synthetic amino acid developed for PET assessment of the anabolic component of tumour metabolism in clinical routine. This phase 1 trial evaluated the safety, tracer stability and uptake kinetics of [(18)F]fluciclovine in patients. Six patients with biopsy-proven prostate cancer were investigated with 3-T MRI and PET/CT. All underwent dynamic [(18)F]fluciclovine PET/CT of the pelvic area for up to 120 min after injection of 418 ± 10 MBq of tracer with simultaneous blood sampling of radioactivity. The kinetics of uptake in tumours and normal tissues were evaluated using standardized uptake values (SUVs) and compartmental modelling. Tumour deposits as defined by MRI were clearly visualized by PET. Urine excretion was minimal and normal tissue background was low. Uptake of [(18)F]fluciclovine in tumour from the blood was rapid and the tumour-to-normal tissue contrast was highest between 1 and 15 min after injection with a 65 % reduction in mean tumour uptake at 90 min after injection. A one-compartment model fitted the tracer kinetics well. Early SUVs correlated well with both the influx rate constant (K (1)) and the volume of distribution of the tracer (V (T)). There were no signs of tracer metabolite formation. The product was well tolerated in all patients without significant adverse events. [(18)F]Fluciclovine shows high uptake in prostate cancer deposits and appears safe for use in humans. The production is robust and the formulation stable in vivo. An early imaging window seems to provide the best visual results. SUV measurements capture most of the kinetic information that can be obtained from more advanced models, potentially simplifying quantification in future studies.
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Lotfian, M; Kharazi, M R; Mirbagheri, A; Dadashi, F; Nourian, R; Mirbagheri, M M
2017-07-01
We aimed to investigate the effects of the lower body weight support treadmill (AlterG) training on kinetics and kinematics of the lower extremities in children with cerebral palsy (CP). We provided a 45-minute training program, 3 times a week for 8 weeks. AlterG can support the subject's weight up to 70% so that the subject will be able to walk more comfortably to reach a more correct walking pattern. The kinematics and kinetics were evaluated using an isokinetic dynamometer. The locomotion parameters were assessed in the gait laboratory. Subjects performance was evaluated at four time points: baseline (prior to training), 1 and 2 months after the beginning of training, and one month after the end of the training (as a follow-up evaluation). The results showed that the major gait, kinematic, and kinetic parameters improved after the AlterG training and were persistent. These findings suggest that the AlterG training can be considered as a therapeutic tool for improving the lower limb performance and locomotion in children with CP.
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Kinetic and Potential Sputtering of Lunar Regolith: Contribution of Solar-Wind Heavy Ions
NASA Technical Reports Server (NTRS)
Meyer, F. W.; Harris, P. R.; Meyer, H. M., III; Hijiazi, H.; Barghouty, A. F.
2013-01-01
Sputtering of lunar regolith by protons as well as solar-wind heavy ions is considered. From preliminary measurements of H+, Ar+1, Ar+6 and Ar+9 ion sputtering of JSC-1A AGGL lunar regolith simulant at solar wind velocities, and TRIM simulations of kinetic sputtering yields, the relative contributions of kinetic and potential sputtering contributions are estimated. An 80-fold enhancement of oxygen sputtering by Ar+ over same-velocity H+, and an additional x2 increase for Ar+9 over same-velocity Ar+ was measured. This enhancement persisted to the maximum fluences investigated is approximately 1016/cm (exp2). Modeling studies including the enhanced oxygen ejection by potential sputtering due to the minority heavy ion multicharged ion solar wind component, and the kinetic sputtering contribution of all solar wind constituents, as determined from TRIM sputtering simulations, indicate an overall 35% reduction of near-surface oxygen abundance. XPS analyses of simulant samples exposed to singly and multicharged Ar ions show the characteristic signature of reduced (metallic) Fe, consistent with the preferential ejection of oxygen atoms that can occur in potential sputtering of some metal oxides.
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Nice, Timothy J.; Strong, David W.; McCune, Broc T.; Pohl, Calvin S.
2013-01-01
Human norovirus (HuNoV) is the major cause of acute nonbacterial gastroenteritis worldwide but has no clear animal reservoir. HuNoV can persist after the resolution of symptoms, and this persistence may be essential for viral maintenance within the population. Many strains of the related murine norovirus (MNV) also persist, providing a tractable animal model for studying norovirus (NoV) persistence. We have used recombinant cDNA clones of representative persistent (CR6) and nonpersistent (CW3) strains to identify a domain within the nonstructural gene NS1/2 that is necessary and sufficient for persistence. Furthermore, we found that a single change of aspartic acid to glutamic acid in CW3 NS1/2 was sufficient for persistence. This same conservative change also caused increased growth of CW3 in the proximal colon, which we found to be a major tissue reservoir of MNV persistence, suggesting that NS1/2 determines viral tropism that is necessary for persistence. These findings represent the first identified function for NoV NS1/2 during infection and establish a novel model system for the study of enteric viral persistence. PMID:23077309
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[A case of invasion of the hyaloid artery into the lens].
Machida, H; Watanabe, I
1992-11-01
A 6-year-old boy with hyaloid artery invasion into the crystalline lens is reported. Both lenses had localized opacities and some brown membranous tissue attached to the posterior lens capsule. He had bilateral persistent hyaloid arteries, and in the right eye this vessel penetrated the lens capsule and invaded the lens. The lens opacity had not increased for 6 years. In persistent hyperplastic primary vitreous we can often see the invasion of fibrovascular tissue into the lens, and this process usually leads to destruction and absorption of the lens. This is an unusual case because the lens showed no significant changes for long period of time in spite of vascular invasion into the lens.
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Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.
2012-01-01
Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.
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Xu, Jian; Murata, Daisuke; Ueda, Jumpei; Viana, Bruno; Tanabe, Setsuhisa
2018-05-07
Persistent luminescence (PersL) imaging without real-time external excitation has been regarded as the next generation of autofluorescence-free optical imaging technology. However, to achieve improved imaging resolution and deep tissue penetration, developing new near-infrared (NIR) persistent phosphors with intense and long duration PersL over 1000 nm is still a challenging but urgent task in this field. Herein, making use of the persistent energy transfer process from Cr 3+ to Er 3+ , we report a novel garnet persistent phosphor of Y 3 Al 2 Ga 3 O 12 codoped with Er 3+ and Cr 3+ (YAG G:Er-Cr), which shows intense Cr 3+ PersL (∼690 nm) in the deep red region matching well with the first biological window (NIR-I, 650-950 nm) and Er 3+ PersL (∼1532 nm) in the NIR region matching well with the third biological window (NIR-III, 1500-1800 nm). The optical imaging through raw-pork tissues (thickness of 1 cm) suggests that the emission band of Er 3+ can achieve higher spatial resolution and more accurate signal location than that of Cr 3+ due to the reduced light scattering at longer wavelengths. Furthermore, by utilizing two independent electron traps with two different trap depths in YAG G:Er-Cr, the Cr 3+ /Er 3+ PersL can even be recharged in situ by photostimulation with 660 nm LED thanks to the redistribution of trapped electrons from the deep trap to the shallow one. Our results serve as a guide in developing promising NIR (>1000 nm) persistent phosphors for long-term optical imaging.
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Długosz, Maciej; Żmudzki, Paweł; Kwiecień, Anna; Szczubiałka, Krzysztof; Krzek, Jan; Nowakowska, Maria
2015-11-15
Photocatalytic degradation of an antibiotic, sulfamethoxazole (SMX), in aqueous solution using a novel floating TiO2-expanded perlite photocatalyst (EP-TiO2-773) and radiation from the near UV spectral range was studied. The process is important considering that SMX is known to be a widespread and highly persistent pollutant of water resources. SMX degradation was described using a pseudo-first-order kinetic equation according to the Langmuir-Hinshelwood model. The products of the SMX photocatalytic degradation were identified. The effect of pH on the kinetics and mechanism of SMX photocatalytic degradation was explained. Copyright © 2015 Elsevier B.V. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
Human enteric viruses are one of the main causative agents of shellfish associated outbreaks. In this study, the kinetics of viral bioaccumulation in live oysters and the heat stability of the most predominant enteric viruses were determined in both tissue culture and in oyster tissues. A human nor...
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Zhou, Qiong; Zheng, Zhijie; Xia, Bijun; Tang, Lan; Lv, Chang; Liu, Wei; Liu, Zhongqiu; Hu, Ming
2010-01-01
Purposes Glucuronidation via UDP-glucuronosyltransferases (or UGTs) is a major metabolic pathway. The purposes of this study are to determine the UGT-isoform specific metabolic fingerprint (or GSMF) of wogonin and oroxylin A, and to use isoform-specific metabolism rates and kinetics to determine and describe their glucuronidation behaviors in tissue microsomes. Methods In vitro glucuronidation rates and profiles were measured using expressed UGTs and human intestinal and liver microsomes. Results GSMF experiments indicated that both flavonoids were metabolized mainly by UGT1As, with major contributions from UGT1A3 and UGT1A7-1A10. Isoform-specific metabolism showed that kinetic profiles obtained using expressed UGT1A3 and UGT1A7-1A10 could fit to known kinetic models. Glucuronidation of both flavonoids in human intestinal and liver microsomes followed simple Michaelis-Menten kinetics. A comparison of the kinetic parameters and profiles suggests that UGT1A9 is likely the main isoform responsible for liver metabolism. In contrast, a combination of UGT1As with a major contribution from UGT1A10 contributed to their intestinal metabolism. Correlation studies clearly showed that UGT isoform-specific metabolism could describe their metabolism rates and profiles in human liver and intestinal microsomes. Conclusion GSMF and isoform-specific metabolism profiles can determine and describe glucuronidation rates and profiles in human tissue microsomes. PMID:20411407
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Jeong, Yoo-Seong; Yim, Chang-Soon; Ryu, Heon-Min; Noh, Chi-Kyoung; Song, Yoo-Kyung; Chung, Suk-Jae
2017-06-01
The objective of the current study was to determine the minimum permeability coefficient, P, needed for perfusion-limited distribution in PBPK. Two expanded kinetic models, containing both permeability and perfusion terms for the rate of tissue distribution, were considered: The resulting equations could be simplified to perfusion-limited distribution depending on tissue permeability. Integration plot analyses were carried out with theophylline in 11 typical tissues to determine their apparent distributional clearances and the model-dependent permeabilities of the tissues. Effective surface areas were calculated for 11 tissues from the tissue permeabilities of theophylline and its PAMPA P. Tissue permeabilities of other drugs were then estimated from their PAMPA P and the effective surface area of the tissues. The differences between the observed and predicted concentrations, as expressed by the sum of squared log differences with the present models were at least comparable to or less than the values obtained using the traditional perfusion-limited distribution model for 24 compounds with diverse PAMPA P values. These observations suggest that the use of a combination of the proposed models, PAMPA P and the effective surface area can be used to reasonably predict the pharmacokinetics of 22 out of 24 model compounds, and is potentially applicable to calculating the kinetics for other drugs. Assuming that the fractional distribution parameter of 80% of the perfusion rate is a reasonable threshold for perfusion-limited distribution in PBPK, our theoretical prediction indicates that the pharmacokinetics of drugs having an apparent PAMPA P of 1×10 -6 cm/s or more will follow the traditional perfusion-limited distribution in PBPK for major tissues in the body. Copyright © 2017 Elsevier B.V. All rights reserved.
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Image-based modeling of tumor shrinkage in head and neck radiation therapy1
Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei
2010-01-01
Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569
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Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics
Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.
2013-01-01
The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100
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DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J
1988-01-01
Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.
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Uniqueness of thermodynamic projector and kinetic basis of molecular individualism
NASA Astrophysics Data System (ADS)
Gorban, Alexander N.; Karlin, Iliya V.
2004-05-01
Three results are presented: First, we solve the problem of persistence of dissipation for reduction of kinetic models. Kinetic equations with thermodynamic Lyapunov functions are studied. Uniqueness of the thermodynamic projector is proven: There exists only one projector which transforms any vector field equipped with the given Lyapunov function into a vector field with the same Lyapunov function for a given anzatz manifold which is not tangent to the Lyapunov function levels. Second, we use the thermodynamic projector for developing the short memory approximation and coarse-graining for general nonlinear dynamic systems. We prove that in this approximation the entropy production increases. ( The theorem about entropy overproduction.) In example, we apply the thermodynamic projector to derive the equations of reduced kinetics for the Fokker-Planck equation. A new class of closures is developed, the kinetic multipeak polyhedra. Distributions of this type are expected in kinetic models with multidimensional instability as universally as the Gaussian distribution appears for stable systems. The number of possible relatively stable states of a nonequilibrium system grows as 2 m, and the number of macroscopic parameters is in order mn, where n is the dimension of configuration space, and m is the number of independent unstable directions in this space. The elaborated class of closures and equations pretends to describe the effects of “molecular individualism”. This is the third result.
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Lifetime and dissolution kinetics of zinc oxide nanoparticles in aqueous media
NASA Astrophysics Data System (ADS)
Wang, Ning; Tong, Tiezheng; Xie, Minwei; Gaillard, Jean-François
2016-08-01
We have assessed the persistence and lifetime of ZnO nanoparticles (ZnO-NPs) by performing dissolution experiments in three different aqueous media. These experiments were performed at ZnO-NP concentration levels close to the solubility of zincite (˜8 μM or 650 μg l-1 of ZnO)—a concentration that is orders of magnitude higher than current estimated relevant environmental concentrations. The kinetics were followed by voltammetry, while maintaining the pH at about 7.5 using a CO2/N2 gas mixture to remove di-oxygen interference. Our results show that, under these conditions, ZnO-NPs readily dissolve with a lifetime expectancy that does not exceed 90 min. Water chemistry, especially the presence of dissolved organic matter (DOM), plays an important role in ZnO-NP dissolution. Dissolution rates significantly increase in the presence of strong chelating agents, EDTA and L-cysteine, while the addition of polymeric DOM, such as sodium alginate, has the opposite effect. Our results suggest that ZnO-NPs are unlikely to persist in natural aqueous media and that the toxicity should be primarily related to the released Zn2+ ions rather than effects commonly associated to the presence of nanoparticles.
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Heterogeneous oxidation of folpet and dimethomorph by OH radicals: A kinetic and mechanistic study
NASA Astrophysics Data System (ADS)
Al Rashidi, M.; Chakir, A.; Roth, E.
2014-01-01
This study investigates the heterogeneous OH oxidation of folpet and dimethomorph, two fungicides identified in the atmosphere of the Champagne-Ardenne region. Kinetic experiments were conducted in the relative mode, using terbuthylazine as a reference compound. The experimental method employed makes use of a simulation chamber coupled to a GC/MS analytical system. Meanwhile, the identification of (4-chlorophenyl)(3,4-dimethoxyphenyl)methanone (CPMPM), a degradation product of the OH oxidation of dimethomorph, is achieved using SPME/GC/MS. Moreover, a degradation mechanism of dimethomorph is proposed, and the heterogeneous OH reactivity of CPMPM is evaluated. The obtained OH reaction rate constants (cm3 molecule-1 s-1) are: kZ-dimethomorph = (2.0 ± 1.2) 10-14, kE-dimethomorph = (1.7 ± 1.2) 10-14, kFolpet = (1.6 ± 0.9) 10-13 and kCPMPM = (1.9 ± 1.0) 10-12. The implicated tropospheric life-times are up to 2 months, which shows that the investigated pesticides are relatively persistent towards oxidation removal processes. CPMPM, the identified product of OH oxidation of dimethomorph, is less persistent with a life time of only 6 days relative to heterogeneous oxidation by OH radicals.
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Threshold for extinction and survival in stochastic tumor immune system
NASA Astrophysics Data System (ADS)
Li, Dongxi; Cheng, Fangjuan
2017-10-01
This paper mainly investigates the stochastic character of tumor growth and extinction in the presence of immune response of a host organism. Firstly, the mathematical model describing the interaction and competition between the tumor cells and immune system is established based on the Michaelis-Menten enzyme kinetics. Then, the threshold conditions for extinction, weak persistence and stochastic persistence of tumor cells are derived by the rigorous theoretical proofs. Finally, stochastic simulation are taken to substantiate and illustrate the conclusion we have derived. The modeling results will be beneficial to understand to concept of immunoediting, and develop the cancer immunotherapy. Besides, our simple theoretical model can help to obtain new insight into the complexity of tumor growth.
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USDA-ARS?s Scientific Manuscript database
Data are presented on the fish tissue concentrations of persistent organic compounds and alkylphenol and alkylphenol ethoxylates (APEs) in large-mouth bass collected from a waste water dominated stream in downtown Chicago. The fish residue concentrations of APEs are compared to concentrations of th...
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Absher, M. P.; Trombley, L.; Hemenway, D. R.; Mickey, R. M.; Leslie, K. O.
1989-01-01
Cristobalite is a crystalline silicon dioxide that elicits pulmonary inflammation and fibrosis in humans and experimental animals. Exposure of rats to aerosols of respirable cristobalite for 8 days led to a rapid influx of neutrophils and macrophages into alveolar and tissue compartments of the lung followed by a more gradual accumulation of T lymphocytes. This inflammatory response persisted throughout 52 weeks after the end of the exposure. For some variables studied there appeared to be a cyclical nature to the response. Statistical analysis of alveolar cell populations and lung tissue weight, protein, and hydroxyproline showed significant time-dependent fluctuations. Histologic analysis revealed a progressive deposition of collagen and type II cell hyperplasia centered on airways, however, there appeared to be some correlation between fluctuations in alveolar cell populations and overall tissue pathology. The observed cellular and biochemical fluctuations and the persistence of the inflammatory response may be due to the presence of silica in the lung, which serves as a source of repetitive stimulation of lung cells. Images Figure 4 Figure 5 PMID:2547319
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A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.
Fennell, T R; Brown, C D
2001-06-15
Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.
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Gallina, G; Lucatello, L; Drigo, I; Cocchi, M; Scandurra, S; Agnoletti, F; Montesissa, C
2010-06-01
Tilmicosin (TIM, Pulmotil) was administered to eight rabbits by oral gavage at a dose of 12.5 mg/kg body weight for 2, 5, and 7 days, and its plasma kinetics and intrapulmonary disposition were investigated. TIM concentrations in plasma samples collected after days 1 and 6 of treatment were measured by high-performance liquid chromatography with ultraviolet detection. The pharmacokinetic parameters, obtained by non-compartmental analysis of TIM plasma concentrations, did not show any significant variations between days 1 and 6. From the second day of treatment, TIM concentrations attained in lung tissue and pulmonary alveolar macrophages (PAM) exceeded those in plasma by 7- and 400-fold, respectively, and high levels were maintained in lung tissues during the entire treatment duration. After the first day of withdrawal, a fast decline in TIM levels in both plasma and lung tissue was observed, but in PAM, much higher concentrations were maintained after 3 days of TIM withdrawal.
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Staszkiewicz, Jaroslaw; Frazier, Trivia P.; Rowan, Brian G.; Bunnell, Bruce A.; Chiu, Ernest S.; Gimble, Jeffrey M.
2010-01-01
Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of stem-like cells that are adherent, clonogenic, and have the ability to self-renew. Previously, we have demonstrated that they can be induced to differentiate into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the current study was to characterize the growth kinetics of the cells and to determine their ability to form colonies of fibroblasts, adipocytes, osteocytes, and chondrocytes. In addition, the immunophenotypes of freshly isolated and culture-expanded cells were evaluated. From 1 g of tissue, we were able to isolate an average of 7.8 × 106 cells exhibiting a cell cycle length of ∼2–3 days. Colony-forming unit (CFU) assays indicated high proliferation potential, and confirmed previously observed multipotentiality of the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were negative for hematopoietic markers (CD4, CD45), proving that they did not derive from circulating hematopoietic cells. The FACS analyses also showed high expression of stem cell antigen-1 (Sca-1) with only a minor population of cells expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker. Additionally, flow cytometry data revealed that the expression patterns of hematopoietic, stromal, and stem cell markers were maintained in the passaged EMSCs, consistent with the persistence of an undifferentiated state. This study indicates that EMSCs provide an alternative model for in vitro analyses of adult mesenchymal stem cells (MSCs). Further studies will be necessary to determine their utility for tissue engineering and regenerative medical applications. PMID:19400629
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Forster, O V; Tsarev, O A; Shvarts, Iu G
2006-01-01
To determine interrelationship between lower limb varicosity, the clinical grade of non-differentiated dysplasia of the connective tissue and atrial fibrillation in patients with coronary artery disease (CAD). Altogether 156 coronary patients were examined. Persistent atrial fibrillation was present in 58 and chronic in 38 patients. The reference group comprised 60 patients without evident rhythm disorders in persons suffering from CAD. Markers of connective tissue dysplasia (
) were revealed on the part of the skeleton, joints skin and visceral organs. Lower limb varicosity was recorded as well. The number of the stigmas in the study groups was different. So, in the patient group without rhythm disorders, the mean number of the stigmas was equal to 3, which is a variant of normal. In the groups with persistent and constant AF, this indicator was equal to 4.7 and 5.2 respectively (p<0.05). The number of patients with evident signs of CID (the number of stigmas 5) was greater in the groups with AP than among patients with normal rhythm. Varicosity was recorded in 41% of both group patients. It is to be noted that in the group with normal rhythm, lower limb varicosity was encountered in 22.1% of cases whereas in the group with AF, in 58.4% of cases with persistent AF and in 41% of cases with constant AF. The mean number of stigmas in the group without varicosity accounted for 3.6 and in patients with varicosity - for 5 (P<0.05). When coronary artery disease is coupled with atrial fibrilation there is a direct close correlation between the signs of connective tissue dysplasia and lower limb varicosity. In patients with persistent AF lower limb varicosity occurs more frequently than in CAD patients with normal rhythm. -
Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Charleston, Bryan; Juleff, Nicholas
2016-05-15
Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Tichauer, Kenneth M.; Wang, Yu; Pogue, Brian W.; Liu, Jonathan T. C.
2015-01-01
The development of methods to accurately quantify cell-surface receptors in living tissues would have a seminal impact in oncology. For example, accurate measures of receptor density in vivo could enhance early detection or surgical resection of tumors via protein-based contrast, allowing removal of cancer with high phenotype specificity. Alternatively, accurate receptor expression estimation could be used as a biomarker to guide patient-specific clinical oncology targeting of the same molecular pathway. Unfortunately, conventional molecular contrast-based imaging approaches are not well adapted to accurately estimating the nanomolar-level cell-surface receptor concentrations in tumors, as most images are dominated by nonspecific sources of contrast such as high vascular permeability and lymphatic inhibition. This article reviews approaches for overcoming these limitations based upon tracer kinetic modeling and the use of emerging protocols to estimate binding potential and the related receptor concentration. Methods such as using single time point imaging or a reference-tissue approach tend to have low accuracy in tumors, whereas paired-agent methods or advanced kinetic analyses are more promising to eliminate the dominance of interstitial space in the signals. Nuclear medicine and optical molecular imaging are the primary modalities used, as they have the nanomolar level sensitivity needed to quantify cell-surface receptor concentrations present in tissue, although each likely has a different clinical niche. PMID:26134619
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Li, Kai; Zhang, Peng; Ge, Linke; Ren, Honglei; Yu, Chunyan; Chen, Xiaoyang; Zhao, Yuanfeng
2014-09-01
Thiamphenicol and florfenicol are two phenicol antibiotics widely used in aquaculture and are ubiquitous as micropollutants in surface waters. The present study investigated their photodegradation kinetics, hydroxyl-radical (OH) oxidation reactivities and products. Firstly, the photolytic kinetics of the phenicols in pure water was studied as a function of initial concentrations (C0) under UV-vis irradiation (λ>200nm). It was found that the kinetics was influenced by C0. A linear plot of the pseudo-first-order rate constant vs C0 was observed with a negative slope. Secondly, the reaction between the phenicol antibiotics and OH was examined with a competition kinetic method under simulated solar irradiation (λ>290nm), which quantified their bimolecular reaction rate constants of (2.13±0.02)×10(9)M(-1)s(-1) and (1.82±0.10)×10(9)M(-1)s(-1) for thiamphenicol and florfenicol, respectively. Then the corresponding OH oxidated half-lives in sunlit surface waters were calculated to be 90.5-106.1h. Some main intermediates were formed from the reaction, which suggested that the two phenicols underwent hydroxylation, oxygenation and dehydrogenation when OH existed. These results are of importance to assess the phenicol persistence in wastewater treatment and sunlit surface waters. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Smirnova, Natalia P; Webb, Brett T; McGill, Jodi L; Schaut, Robert G; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Sacco, Randy E; Hansen, Thomas R
2014-04-01
Development of transplacental infection depends on the ability of the virus to cross the placenta and replicate within the fetus while counteracting maternal and fetal immune responses. Unfortunately, little is known about this complex process. Non-cytopathic (ncp) strains of bovine viral diarrhea virus (BVDV), a pestivirus in the Flaviviridae family, cause persistent infection in early gestational fetuses (<150 days; persistently infected, PI), but are cleared by immunocompetent animals and late gestational fetuses (>150 days; transiently infected, TI). Evasion of innate immune response and development of immunotolerance to ncp BVDV have been suggested as possible mechanisms for the establishment of the persistent infection. Previously we have observed a robust temporal induction of interferon (IFN) type I (innate immune response) and upregulation of IFN stimulated genes (ISGs) in BVDV TI fetuses. Modest chronic upregulation of ISGs in PI fetuses and calves reflects a stimulated innate immune response during persistent BVDV infection. We hypothesized that establishing persistent fetal BVDV infection is also accompanied by the induction of IFN-gamma (IFN-γ). The aims of the present study were to determine IFN-γ concentration in blood and amniotic fluid from control, TI and PI fetuses during BVDV infection and analyze induction of the IFN-γ downstream pathways in fetal lymphoid tissues. Two experiments with in vivo BVDV infections were completed. In Experiment 1, pregnant heifers were infected with ncp BVDV type 2 on day 75 or 175 of gestation or kept naïve to generate PI, TI and control fetuses, respectively. Fetuses were collected by Cesarean section on day 190. In Experiment 2, fetuses were collected on days 82, 89, 97, 192 and 245 following infection of pregnant heifers on day 75 of gestation. The results were consistent with the hypothesis that ncp BVDV infection induces IFN-γ secretion during acute infection in both TI and PI fetuses and that lymphoid tissues such as spleen, liver and thymus, serve both as possible sources of IFN-γ and target organs for its effects. Notably, induction of IFN-γ coincides with a decrease in BVDV RNA concentrations in PI fetal blood and tissues. This is the first report indicating the possible presence of an adaptive immune response in persistent BVDV infections, which may be contributing to the observed reduction of viremia in PI fetuses. Copyright © 2014 Elsevier B.V. All rights reserved.
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Summerhill, Susan; Stroud, Timothy; Nagendra, Roshini; Perros-Huguet, Christelle; Trevethick, Michael
2008-01-01
The aim was to establish a robust, 96-well, cell-based assay to assess the potency and persistence of action of agonists acting at human recombinant beta(2) adrenoceptors expressed in CHO (Chinese Hamster Ovary) cells and to compare this with published duration of action data in guinea pig isolated trachea and human bronchus. Cells were treated with either: (i) beta-adrenoceptor agonist for 30 min, washed and cyclicAMP (cAMP) measured 30 min later-termed 'washed' cells or, (ii) treated with solvent for 30 min, washed, and then treated with beta-adrenoceptor agonist for 30 min and cAMP measured-termed 'unwashed' cells. The 'washed' EC(50) was divided by the 'unwashed' EC(50) to determine a rightward shift concentration ratio, which was indicative of the persistence of action at the receptor. At the beta(2) adrenoceptor salmeterol, carmoterol and indacaterol were resistant to washing with a concentration ratio of <5, indicating a long persistence of action, whereas formoterol, isoprenaline and salbutamol were washed out with a ratio of 32, >294 and >800 respectively, suggesting a shorter persistence of action. At beta(1) and beta(3) adrenoceptors all compounds washed out. The persistent effects of salmeterol at beta(2) following washing could be reversed by the selective beta(2) antagonist ICI 118551, suggesting continued receptor activation. The data presented agree well with published data assessing duration of action of beta(2) agonists in human isolated bronchus and guinea pig isolated trachea. Key features are: (a) it is a 96-well format which can be used to assess many compounds in a single experiment, (b) both potency and persistence of agonist action are assessed in the same assay, (c) any effects of concentration on the persistence of action can be highlighted, and (d) it allows triage of compounds prior to tissue bath studies thus reducing the use of animal tissue.
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The effect of heart motion on parameter bias in dynamic cardiac SPECT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ross, S.G.; Gullberg, G.T.; Huesman, R.H.
1996-12-31
Dynamic cardiac SPECT can be used to estimate kinetic rate parameters which describe the wash-in and wash-out of tracer activity between the blood and the myocardial tissue. These kinetic parameters can in turn be correlated to myocardial perfusion. There are, however, many physical aspects associated with dynamic SPECT which can introduce errors into the estimates. This paper describes a study which investigates the effect of heart motion on kinetic parameter estimates. Dynamic SPECT simulations are performed using a beating version of the MCAT phantom. The results demonstrate that cardiac motion has a significant effect on the blood, tissue, and backgroundmore » content of regions of interest. This in turn affects estimates of wash-in, while it has very little effect on estimates of wash-out. The effect of cardiac motion on parameter estimates appears not to be as great as effects introduced by photon noise and geometric collimator response. It is also shown that cardiac motion results in little extravascular contamination of the left ventricle blood region of interest.« less
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Mercury bioaccumulation and decontamination kinetics in the edible cockle Cerastoderma edule.
Cardoso, P G; Grilo, T F; Pereira, E; Duarte, A C; Pardal, M A
2013-02-01
Mercury bioaccumulation and decontamination kinetics in the edible cockle Cerastoderma edule were studied through a mesocosms experiment after a medium-term exposure to the metal. The results revealed that the bivalve presented distinct bioaccumulation kinetics according to the different tissues. While the gills showed a linear accumulation pattern, the digestive gland and the entire organism presented a saturation model, with higher accumulation during the first 7d of exposure and lower during the rest of the time. In addition, the bioaccumulation rate was not proportional to the Hg concentration, since the organisms under lower contamination presented higher bioconcentration factors than the ones under higher contamination. Gills were the tissues with higher mercury accumulation capability. Concerning the decontamination phase, C. edule lost approximately 80% of the mercury after 24h exposure in clean seawater. Nevertheless, never reached the original condition, showing in the final (20 d detox), Hg levels (>0.5 ppm) higher than those allowed by the legislation regulating human food consumption. This represents a matter of concern for Human health. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Urgast, Dagmar S; Hill, Sarah; Kwun, In-Sook; Beattie, John H; Goenaga-Infante, Heidi; Feldmann, Jörg
2012-10-01
Zinc stable isotope tracers (⁶⁷Zn and ⁷⁰Zn) were injected into rats at two different time points to investigate the feasibility of using tracers to study zinc kinetics at the microscale within distinct tissue features. Laser ablation coupled to multi-collector ICP-MS was used to analyse average isotope ratios in liver thin sections and to generate bio-images showing zinc isotope ratio distribution in brain thin sections. Average isotope ratios of all samples from treated animals were found to be statistically different (P < 0.05) from samples from untreated control animals. Furthermore, differing isotope ratios in physiological features of the brain, namely hippocampus, amygdala, cortex and hypothalamus, were identified. This indicates that these regions differ in their zinc metabolism kinetics. While cortex and hypothalamus contain more tracer two days after injection than 14 days after injection, the opposite is true for hippocampus and amygdala. This study showed that stable isotope tracer experiments can be combined with laser ablation MC-ICP-MS to measure trace element kinetics in tissues at a microscale level.
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2014-01-01
facilitates analysis of fibrin generation and its modulation by clotting factors : implications for hemostasis-enhancing therapies† Alexander Y...investigate the ability of fibrinogen and a recently proposed prothrombin complex concentrate composition, PCC-AT (a combination of the clotting factors II...kinetics. Moreover, the model qualitatively predicted the impact of tissue factor and tPA/tenecteplase level variations on the fibrin output. In the
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Baghdadi, Yaser M K; Morrey, Bernard F; O'Driscoll, Shawn W; Steinmann, Scott P; Sanchez-Sotelo, Joaquin
2014-07-01
Primary reconstruction of the lateral collateral ligament complex (LCLC) using graft tissue restores elbow stability in many, but not all, elbows with acute or chronic posterolateral rotatory instability (PLRI). Revision reconstruction using a tendon allograft is occasionally considered for persistent PLRI, but the outcome of revision ligament reconstruction in this setting is largely unknown. We determined whether revision allograft ligament reconstruction can (1) restore the stability and (2) result in improved elbow scores for patients with persistent PLRI of the elbow after a previous failed primary reconstructive attempt and in the context of the diverse pathology being addressed. Between 2001 and 2011, 160 surgical elbow procedures were performed at our institution for the LCLC reconstruction using allograft tissue. Only patients undergoing revision allograft reconstruction of the LCLC for persistent PLRI with a previous failed primary reconstructive attempt using graft tissue and at least I year of followup were included in the study. Eleven patients (11 elbows) fulfilled our inclusion criteria and formed our study cohort. The cohort consisted of six female patients and five male patients. The mean age at the time of revision surgery was 36 years (range, 14-59 years). The revision allograft reconstruction was carried out after a mean of 3 years (range, 2.5 months to 9 years) from a failed attempted reconstruction of the LCLC. Osseous deficiency to some extent was identified in the preoperative radiographs of eight elbows. Mean followup was 5 years (range, 1-12 years). Revision allograft reconstruction of the LCLC restored elbow stability in eight of the 11 elbows; two of the three elbows with persistent instability were operated on a third time (at 6 and 7 months after allograft revision reconstruction). For elbows with no persistent instability, the mean Mayo Elbow Performance Score at most recent followup was 83 points (range, 60-100 points), and six elbows were rated with a good or excellent result. All patients with persistent instability had some degree of preoperative bone loss. Revision allograft reconstruction of the LCLC is an option for treating recurrent PLRI, although this is a complex and resistant problem, and nearly ½ of the patients in this cohort either had persistent instability and/or had a fair or poor elbow score. Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
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Kinetic chain abnormalities in the athletic shoulder.
Sciascia, Aaron; Thigpen, Charles; Namdari, Surena; Baldwin, Keith
2012-03-01
Overhead activities require the shoulder to be exposed to and sustain repetitive loads. The segmental activation of the body's links, known as the kinetic chain, allows this to occur effectively. Proper muscle activation is achieved through generation of energy from the central segment or core, which then transfers the energy to the terminal links of the shoulder, elbow, and hand. The kinetic chain is best characterized by 3 components: optimized anatomy, reproducible efficient motor patterns, and the sequential generation of forces. However, tissue injury and anatomic deficits such as weakness and/or tightness in the leg, pelvic core, or scapular musculature can lead to overuse shoulder injuries. These injuries can be prevented and maladaptations can be detected with a thorough understanding of biomechanics of the kinetic chain as it relates to overhead activity.
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NASA Technical Reports Server (NTRS)
Foster, B. R.
1974-01-01
Cellular response and cell population kinetics were studied during lymphopoiesis in the thymus of the mouse under continuous gamma irradiation using autoradiographic techniques and specific labeling with tritiated thymidine. On the basis of tissue weights, it is concluded that the response of both the thymus and spleen to continuous low dose-rate irradiation is multiphasic. That is, alternating periods of steady state growth, followed by collapse, which in turn is followed by another period of homeostasis. Since there are two populations of lymphocytes - short lived and long-lived, it may be that different phases of steady state growth are mediated by different lymphocytes. The spleen is affected to a greater extent with shorter periods of steady-state growth than exhibited by the thymus.
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Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study
NASA Technical Reports Server (NTRS)
Foster, B. R.
1975-01-01
A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.
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Warnock, Geoffrey; Sommerauer, Michael; Mu, Linjing; Pla Gonzalez, Gloria; Geistlich, Susanne; Treyer, Valerie; Schibli, Roger; Buck, Alfred; Krämer, Stefanie D; Ametamey, Simon M
2018-06-01
Non-invasive imaging of metabotropic glutamate receptor 5 (mGlu 5 ) in the brain using PET is of interest in e.g., anxiety, depression, and Parkinson's disease. Widespread application of the most widely used mGlu 5 tracer, [ 11 C]ABP688, is limited by the short physical half-life of carbon-11. [ 18 F]PSS232 is a fluorinated analog with promising preclinical properties and high selectivity and specificity for mGlu 5 . In this first-in-man study, we evaluated the brain uptake pattern and kinetics of [ 18 F]PSS232 in healthy volunteers. [ 18 F]PSS232 PET was performed with ten healthy male volunteers aged 20-40 years. Seven of the subjects received a bolus injection and the remainder a bolus/infusion protocol. Cerebral blood flow was determined in seven subjects using [ 15 O]water PET. Arterial blood activity was measured using an online blood counter. Tracer kinetics were evaluated by compartment modeling and parametric maps were generated for both tracers. At 90 min post-injection, 59.2 ± 11.1% of total radioactivity in plasma corresponded to intact tracer. The regional first pass extraction fraction of [ 18 F]PSS232 ranged from 0.41 ± 0.06 to 0.55 ± 0.03 and brain distribution pattern matched that of [ 11 C]ABP688. Uptake kinetics followed a simple two-tissue compartment model. The volume of distribution of total tracer (V T , ml/cm 3 ) ranged from 1.18 ± 0.20 for white matter to 2.91 ± 0.51 for putamen. The respective mean distribution volume ratios (DVR) with cerebellum as the reference tissue were 0.88 ± 0.06 and 2.12 ± 0.10, respectively. The tissue/cerebellum ratios of a bolus/infusion protocol (30/70 dose ratio) were close to the DVR values. Brain uptake of [ 18 F]PSS232 matched the distribution of mGlu 5 and followed a two-tissue compartment model. The well-defined kinetics and the possibility to use reference tissue models, obviating the need for arterial blood sampling, make [ 18 F]PSS232 a promising fluorine-18 labeled radioligand for measuring mGlu 5 density in humans.
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Velocity persistence of Brownian particles generated in a glow discharge
NASA Astrophysics Data System (ADS)
Hurd, Alan J.; Ho, Pauline
1989-06-01
Quasielastic light scattering from Brownian particles in the rarefied environment of a glow discharge exhibits Gaussianlike intensity correlation functions owing to the long mean free paths of the particles. The shape of the correlation function depends on the particles' average thermal velocity and friction coefficient, which can be related to aggregate mass and structure, and indicates a crossover from kinetic to hydrodynamic behavior.
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Effects of Different PER Translational Kinetics on the Dynamics of a Core Circadian Clock Model
Nieto, Paula S.; Revelli, Jorge A.; Garbarino-Pico, Eduardo; Condat, Carlos A.; Guido, Mario E.; Tamarit, Francisco A.
2015-01-01
Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis. PMID:25607544
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Effects of different per translational kinetics on the dynamics of a core circadian clock model.
Nieto, Paula S; Revelli, Jorge A; Garbarino-Pico, Eduardo; Condat, Carlos A; Guido, Mario E; Tamarit, Francisco A
2015-01-01
Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.
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Fan, Zhen; Calsolaro, Valeria; Atkinson, Rebecca A; Femminella, Grazia D; Waldman, Adam; Buckley, Christopher; Trigg, William; Brooks, David J; Hinz, Rainer; Edison, Paul
2016-11-01
Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18 F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (V T ) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with V T in the kinetic model, which could be used for voxelwise analysis. We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18 F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low V T , the methodology presented here forms the basis for quantification for future PET studies using 18 F-GE180 in different pathologies. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Degradation of foot-and-mouth disease virus during composting of infected pig carcasses
Guan, J.; Chan, M.; Grenier, C.; Brooks, B.W.; Spencer, J.L.; Kranendonk, C.; Copps, J.; Clavijo, A.
2010-01-01
The objective of this study was to investigate the inactivation and degradation of foot-and-mouth disease (FMD) virus during composting of infected pig carcasses as measured by virus isolation in tissue culture and by real-time reverse transcriptase polymerase chain reaction (RRT-PCR). Three FMD-infected pig carcasses were composted in a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. Compost temperatures had reached 50°C and 70°C by days 10 and 19, respectively. Under these conditions, FMD virus was inactivated in specimens in compost by day 10 and the viral RNA was degraded in skin and internal organ tissues by day 21. In comparison, at ambient temperatures close to 20°C, FMD virus survived to day 10 in the skin tissue specimen from the pig that had the highest initial level of viral RNA in its tissues and the viral RNA persisted to day 21. Similarly, beta-actin mRNA, tested as a PCR control, persisted to day 21 in specimens held at ambient temperatures, but it was degraded in the remnants of tissues recovered from compost on day 21. Results from this study provide evidence that composting could be used for safe disposal of pig carcasses infected with FMD virus. PMID:20357957
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Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R
2000-01-01
Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.
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Bone Symposium Held in Portland Oregon, on 17-20 July 1991
1992-03-01
removed. Persistent drainage and/or sinus tract(s) are common. Multiple species of bacteria are usually isolated from biopsies of infected granulations...patients even years of intermittent drainage . The possibility of attenuating the infection is reduced when the integrity of the soft tissue surrounding...successful transfers had persistent drainage . Only 12 * patients walked without assistive devices in followup.51 The advantage of the Ilizarov technique is
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Frustration of resonant preheating by exotic kinetic terms
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rahmati, Shohreh; Seahra, Sanjeev S., E-mail: srahmati@unb.ca, E-mail: sseahra@unb.ca
2014-10-01
We study the effects of exotic kinetic terms on parametric resonance during the preheating epoch of the early universe. Specifically, we consider modifications to the action of ordinary matter fields motivated by generalized uncertainty principles, polymer quantization, as well as Dirac-Born-Infeld and k-essence models. To leading order in an ''exotic physics'' scale, the equations of motion derived from each of these models have the same algebraic form involving a nonlinear self-interaction in the matter sector. Neglecting spatial dependence, we show that the nonlinearity effectively shuts down the parametric resonance after a finite time period. We find numeric evidence that themore » frustration of parametric resonance persists to spatially inhomogenous matter in (1+1)-dimensions.« less
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Jensen, Vivi F H; Mølck, Anne-Marie; Berthelsen, Line O; Alifrangis, Lene; Andersen, Lene; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid B
2017-07-01
New insulin analogues with a longer duration of action and a 'peakless' pharmacokinetic profile have been developed to improve efficacy, safety and convenience for patients with diabetes. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In this study, we investigated the effects of persistent IIH and their reversibility in euglycaemic rats. Histopathological changes in insulin-infused animals included partly reversible axonal and reversible myofibre degeneration in peripheral nerve and skeletal muscle tissue, respectively, as well as reversible pancreatic islet atrophy and partly reversible increase in unilocular adipocytes in brown adipose tissue. Additionally, results suggested increased gluconeogenesis. The observed hyperphagia, the pancreatic, peripheral nerve and skeletal muscle changes were considered related to the hypoglycaemia. Cessation of insulin infusion resulted in transient hyperglycaemia, decreased food consumption and body-weight loss before returning to control levels. The implications for the interpretation of non-clinical studies with long-acting insulin analogues are discussed. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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Santón, Almudena; García-Cosio, Mónica; Bellosillo, Beatriz; Rodríguez, Patricia; Cristóbal, Eva; Serrano, Sergio; Besses, Carlos; Abraira, Victor; Salar, Antonio; Montalbán, Carlos
2008-08-01
The purpose of this work was to study retrospectively the molecular response and outcome of 19 gastric mucosa associated lymphoid tissue (MALT) lymphoma patients achieving histological remission after chemotherapy or surgery. Immunoglobulin heavy chain variable (IgV(H)) gene rearrangements were studied by PCR in biopsies obtained at diagnosis and follow-up. Presence of t(11;18)(q21;q21) was studied by FISH or RT-PCR. Sequencing analysis of three t(11;18)(q21;q21) positive and two negative lymphomas with persistent monoclonal IgV(H) rearrangements was also performed. Long-term IgV(H) monoclonality was demonstrated in 11/19 patients (58%); in five of them monoclonal rearrangements were present in all samples throughout the follow-up. Persistent IgV(H) monoclonality was detected a median of 49 months after the achievement of histological response and did not condition histological relapse in most cases. All three t(11;18)(q21;q21) positive patients had maintained IgV(H) monoclonality and sequencing analyses revealed the same mutated IgV(H) alleles in the diagnostic and the follow-up samples. Over half of the patients with gastric MALT lymphoma with histological response after chemotherapy and/or surgery have long-term persistent monoclonality. The presence of t(11;18)(q21;q21) seems to condition long-term persistence of the initial lymphoma clone.trade mark.
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Asson-Batres, Mary Ann; Smith, W. Bradford; Clark, Gale
2009-01-01
Vitamin A (VA), all-trans-retinol (at-ROL), and its derivative, all-trans-retinoic acid (at-RA), are required for neuron development. The effects of these retinoids are dependent upon the nutritional status of the rat and tissue-specific dynamics of retinoid access and utilization. The purpose of this study was to determine the status of at-ROL and at-RA in the peripheral olfactory organ of postnatal rats fed a normal diet and rats fed a VA-deficient (VAD) diet. Extracted retinoids were analyzed by HPLC. Resolved sample peaks were identified by comparing their elution times and spectra with those of authentic standards. Mean at-RA and at-ROL concentrations of 23 pmol/g olfactory tissue and 0.13 nmol/g, respectively, were recovered from olfactory tissue. The ratio of at-RA:at-ROL in olfactory was ∼2 times that in testis and 200 times that in liver. at-ROL was depleted from the liver and olfactory organ of rats fed a VAD diet from birth to 70 d of age. Surprisingly, at-RA was still present in olfactory tissue from these rats. At 90 d of age, the VAD rats were frankly deficient and at-RA was no longer detectable in olfactory tissue. The comparatively high ratio of at-RA:at-ROL in the peripheral olfactory organ and the persistence of at-RA in at-ROL-depleted tissues strongly suggests that maintenance of local stores of at-RA is functionally relevant in this tissue. PMID:19403718
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Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs.
Moyron-Quiroz, Juan E; Rangel-Moreno, Javier; Hartson, Louise; Kusser, Kim; Tighe, Michael P; Klonowski, Kimberly D; Lefrançois, Leo; Cauley, Linda S; Harmsen, Allen G; Lund, Frances E; Randall, Troy D
2006-10-01
Secondary lymphoid organs (SLOs) promote primary immune responses by recruiting naive lymphocytes and activated APCs. However, their role in the persistence or responsiveness of memory lymphocytes is unclear. We tested whether memory cells were maintained and could respond to challenge in the absence of SLOs. We found that influenza-specific CD8 cells in the lung acquired a memory phenotype, underwent homeostatic proliferation, recirculated through nonlymphoid tissues, and responded to and cleared a challenge infection in the complete absence of SLOs. Similarly, influenza-specific virus-neutralizing antibody was generated and maintained in the absence of SLOs. Inducible bronchus-associated lymphoid tissue (iBALT) was also formed in the lungs of previously infected mice and may provide a niche for the maintenance of memory cells at the local level. These data show that SLOs are dispensable for the maintenance of immunologic memory and directly demonstrate the utility of local tissues, such as iBALT, in secondary immune responses.
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Interfacial mixing in high energy-density matter with a multiphysics kinetic model
NASA Astrophysics Data System (ADS)
Haack, Jeff; Hauck, Cory; Murillo, Michael
2017-10-01
We have extended a recently-developed multispecies, multitemperature BGK model to include multiphysics capability that allows modeling of a wider range of plasma conditions. In particular, we have extended the model to describe one spatial dimension, and included a multispecies atomic ionization model, accurate collision physics across coupling regimes, self-consistent electric fields, and degeneracy in the electronic screening. We apply the new model to a warm dense matter scenario in which the ablator-fuel interface of an inertial confinement fusion target is heated, similar to a recent molecular dynamics study, but for larger length and time scales and for much higher temperatures. From our numerical results we are able to explore a variety of phenomena, including hydrogen jetting, kinetic effects (non-Maxwellian and anisotropic distributions), plasma physics (size, persistence and role of electric fields) and transport (relative sizes of Fickean diffision, electrodiffusion and barodiffusion). As compared with the recent molecular dynamics work the kinetic model greatly extends the accessible physical domains we are able to model.
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Multi-scale kinetics of a field-directed colloidal phase transition.
Swan, James W; Vasquez, Paula A; Whitson, Peggy A; Fincke, E Michael; Wakata, Koichi; Magnus, Sandra H; De Winne, Frank; Barratt, Michael R; Agui, Juan H; Green, Robert D; Hall, Nancy R; Bohman, Donna Y; Bunnell, Charles T; Gast, Alice P; Furst, Eric M
2012-10-02
Polarizable colloids are expected to form crystalline equilibrium phases when exposed to a steady, uniform field. However, when colloids become localized this field-induced phase transition arrests and the suspension persists indefinitely as a kinetically trapped, percolated structure. We anneal such gels formed from magneto-rheological fluids by toggling the field strength at varied frequencies. This processing allows the arrested structure to relax periodically to equilibrium--colloid-rich, cylindrical columns. Two distinct growth regimes are observed: one in which particle domains ripen through diffusive relaxation of the gel, and the other where the system-spanning structure collapses and columnar domains coalesce apparently through field-driven interactions. There is a stark boundary as a function of magnetic field strength and toggle frequency distinguishing the two regimes. These results demonstrate how kinetic barriers to a colloidal phase transition are subverted through measured, periodic variation of driving forces. Such directed assembly may be harnessed to create unique materials from dispersions of colloids.
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Fibril growth kinetics link buffer conditions and topology of 3D collagen I networks.
Kalbitzer, Liv; Pompe, Tilo
2018-02-01
Three-dimensional fibrillar networks reconstituted from collagen I are widely used as biomimetic scaffolds for in vitro and in vivo cell studies. Various physicochemical parameters of buffer conditions for in vitro fibril formation are well known, including pH-value, ion concentrations and temperature. However, there is a lack of a detailed understanding of reconstituting well-defined 3D network topologies, which is required to mimic specific properties of the native extracellular matrix. We screened a wide range of relevant physicochemical buffer conditions and characterized the topology of the reconstituted 3D networks in terms of mean pore size and fibril diameter. A congruent analysis of fibril formation kinetics by turbidimetry revealed the adjustment of the lateral growth phase of fibrils by buffer conditions to be key in the determination of pore size and fibril diameter of the networks. Although the kinetics of nucleation and linear growth phase were affected by buffer conditions as well, network topology was independent of those two growth phases. Overall, the results of our study provide necessary insights into how to engineer 3D collagen matrices with an independent control over topology parameters, in order to mimic in vivo tissues in in vitro experiments and tissue engineering applications. The study reports a comprehensive analysis of physicochemical conditions of buffer solutions to reconstitute defined 3D collagen I matrices. By a combined analysis of network topology, i.e., pore size and fibril diameter, and the kinetics of fibril formation we can reveal the dependence of 3D network topology on buffer conditions, such as pH-value, phosphate concentration and sodium chloride content. With those results we are now able to provide engineering strategies to independently tune the topology parameters of widely used 3D collagen scaffolds based on the buffer conditions. By that, we enable the straightforward mimicking of extracellular matrices of in vivo tissues for in vitro cell culture experiments and tissue engineering applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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Cell Population Kinetics of Collagen Scaffolds in Ex Vivo Oral Wound Repair
Agis, Hermann; Collins, Amy; Taut, Andrei D.; Jin, Qiming; Kruger, Laura; Görlach, Christoph; Giannobile, William V.
2014-01-01
Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds. PMID:25397671
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Eschbaumer, Michael; Stenfeldt, Carolina; Smoliga, George R.; ...
2016-09-19
In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A 24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carrierswere further compared to 2 naive animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and amore » minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers.Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly over represented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E 2 production and the induction of regulatoryT cells were over expressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Furthermore, based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatoryT cells.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Eschbaumer, Michael; Stenfeldt, Carolina; Smoliga, George R.
In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A 24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carrierswere further compared to 2 naive animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and amore » minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers.Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly over represented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E 2 production and the induction of regulatoryT cells were over expressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Furthermore, based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatoryT cells.« less
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Schenk, Thomas; Enders, Martin; Pollak, Stefan; Hahn, Ralph; Huzly, Daniela
2009-01-01
Human parvovirus B19 has been linked to a variety of cardiac diseases, as well as to erythema infectiosum, acute arthropathy, and fetal hydrops. A causal association between viral infection and cardiac disease was frequently postulated following the detection of B19 DNA by PCR in endomyocardial biopsy specimens. Since the lifelong persistence of B19 DNA in bone marrow, skin, synovia, tonsils, and liver was previously reported, the aim of our study was to investigate the possibility of asymptomatic B19 DNA persistence in heart tissue. Myocardial autopsy and postmortem blood samples were prospectively collected from 69 bodies sent to the Department of Forensic Medicine, Freiburg University Medical Center, for inquests. All study subjects were screened for B19-specific antibodies using a commercial enzyme immunoassay. Tissue samples were analyzed by real-time PCR for the presence of viral DNA. Since the presence of B19 genotype 2, known to have been circulating before 1960, would prove long-lasting persistence, the presence of the B19 genotype was retrospectively determined in seven of the study subjects by melting temperature analysis and sequencing of the PCR product. B19 DNA was found in myocardial samples from 46 of 48 seropositive and in none of 21 seronegative individuals. B19 genotype 1 was found in three patients born between 1950 and 1969. Genotype 2 was found in four patients born between 1927 and 1957. Our findings suggest lifelong persistence of B19 DNA in heart tissue. Thus, the detection of B19 DNA in myocardial biopsy specimens alone is not sufficient to postulate a relationship between B19 infection and cardiac disease. PMID:19005147
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Anderson, Donald S.; Patchin, Esther S.; Silva, Rona M.; Uyeminami, Dale L.; Sharmah, Arjun; Guo, Ting; Das, Gautom K.; Brown, Jared M.; Shannahan, Jonathan; Gordon, Terry; Chen, Lung Chi; Pinkerton, Kent E.; Van Winkle, Laura S.
2015-01-01
The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m3, respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days). PMID:25577195
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Recruiting at the Edge: Kinetic Energy Inhibits Anchovy Populations in the Western Mediterranean
Ruiz, Javier; Macías, Diego; Rincón, Margarita M.; Pascual, Ananda; Catalán, Ignacio A.; Navarro, Gabriel
2013-01-01
The Strait of Gibraltar replenishes the Mediterranean with Atlantic waters through an intense eastward current known as the Atlantic Jet (AJ). The AJ fertilizes the southwestern Mediterranean and is considered to be the ultimate factor responsible for the comparatively high fish production of this region. Here, we perform an analysis of the available historical catches and catch per unit effort (CPUE), together with a long series of surface currents, kinetic energy and chlorophyll concentration. We show that the high kinetic energy of the AJ increases primary production but also negatively impacts the recruitment of anchovy. We contend that anchovy recruitment in the region is inhibited by the advection and dispersion of larvae and post-larvae during periods of strong advection by the AJ. The inhibitory impact of kinetic energy on anchovy landings is not a transient but rather a persistent state of the system. An exceptional combination of events creates an outbreak of this species in the Alboran Sea. These events depend on the Mediterranean-Atlantic exchange of water masses and, therefore, are highly sensitive to climate changes that are projected, though not always negatively, for fish landings. PMID:23451027
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Stamenković, Stefan; Pavićević, Aleksandra; Mojović, Miloš; Popović-Bijelić, Ana; Selaković, Vesna; Andjus, Pavle; Bačić, Goran
2017-07-01
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1 G93A ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP). Additionally, the redox status of the two brain regions previously implicated in disease pathology, brainstem and hippocampus, was investigated by spectrophotometric biochemical assays. The EPR results indicated that among the three spin probes, 3CP is the most suitable for reporting the intracellular redox status changes, as Tempol was reduced in vivo within minutes (t 1/2 =2.0±0.5min), thus preventing reliable kinetic modeling, whereas 3CxP reduction kinetics gave divergent conclusions, most probably due to its membrane impermeability. It was observed that the reduction kinetics of 3CP in vivo, in the head of preALS and ALS SOD1 G93A rats was altered compared to the controls. Pharmacokinetic modeling of 3CP reduction in vivo, revealed elevated tissue distribution and tissue reduction rate constants indicating an altered brain tissue redox status, and possibly BBB disruption in these animals. The preALS and ALS brain tissue homogenates also showed increased nitrilation, superoxide production, lipid peroxidation and manganese superoxide dismutase activity, and a decreased copper-zinc superoxide dismutase activity. The present study highlights in vivo EPR spectroscopy as a reliable tool for the investigation of changes in BBB permeability and for the unprecedented in vivo monitoring of the brain tissue redox status, as early markers of ALS. Copyright © 2017 Elsevier Inc. All rights reserved.
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A kinetic study of bitter taste receptor sensing using immobilized porcine taste bud tissues.
Wei, Lihui; Qiao, Lixin; Pang, Guangchang; Xie, Junbo
2017-06-15
At present, developing an efficient assay method for truly reflecting the real feelings of gustatory tissues is of great importance. In this study, a novel biosensor was fabricated to investigate the kinetic characteristics of the receptors in taste bud tissues sensing bitter substances for the first time. Porcine taste bud tissues were used as the sensing elements, and the sandwich-type sensing membrane was fixed onto a glassy carbon electrode for assembling the biosensor. With the developed sensor, the response currents induced by sucrose octaacetate, denatonium benzoate, and quercetin stimulating corresponding receptors were determined. The results demonstrated that the interaction between the analyst with their receptors were fitting to hyperbola (R 2 =0.9776, 0.9980 and 0.9601), and the activation constants were 8.748×10 -15 mol/L, 1.429×10 -12 mol/L, 6.613×10 -14 mol/L, respectively. The average number of receptors per cell was calculated as 1.75, 28.58, and 13.23, while the signal amplification factors were 1.08×10 4 , 2.89×10 3 and 9.76×10 4 . These suggest that the sensor can be used to quantitatively describe the interaction characteristics of cells or tissue receptors with their ligands, the role of cellular signaling cascade, the number of receptors, and the signal transmission pathways. Copyright © 2017 Elsevier B.V. All rights reserved.
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Photothermally induced delayed tissue death.
Gordon, Jeffrey M; Shaco-Levy, Ruthy; Feuermann, Daniel; Huleihil, Mahmoud; Mizrahi, Solly
2006-01-01
We report pronounced delayed tissue death in photothermal surgery performed on the livers of live healthy rats with highly concentrated sunlight (ultrabright noncoherent light). Exposure times and power levels were selected to produce immediate necroses of the order of hundreds of cubic millimeters. Pathology reveals that lesion volumes increase by up to a factor of 5 within approximately 24 h after surgery, and then stabilize. Islands of viable cells can persist within damaged tissue, in the immediate vicinity of blood vessels, but also necrose within about 48 h.
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Najera-Hernandez, Salustio; Sanchez-Alonso, Maria Patricia; Anastacio-Marcelino, Estela; Negrete-Abascal, Erasmo
2018-01-01
ABSTRACT The draft genome sequence of Escherichia coli strain SN137 is reported here. The genome comprises 172 contigs, corresponding to 4.9 Mb with 50% G+C content, and contains several genes related to pathogenicity that explain its survival in human hematic tissue. PMID:29348341
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Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.
Pallikkuth, Suresh; Mohan, Mahesh
2015-12-01
This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Bergsbaken, Tessa; Bevan, Michael J; Fink, Pamela J
2017-04-04
Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8 + T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103 - CD69 + Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT) cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103 - CD69 + Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2 + IL-12-producing cells reduced the size of the CD103 - Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.
Perry, Donna L; Huzella, Louis M; Bernbaum, John G; Holbrook, Michael R; Jahrling, Peter B; Hagen, Katie R; Schnell, Matthias J; Johnson, Reed F
2018-03-01
Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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Das, Amal Chandra; Debnath, Anjan; Mukherjee, Debatosh
2003-10-01
A field experiment has been conducted with two herbicides viz. oxadiazon [5-terbutyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-one] and oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenyl)-4-(trifluoromethyl) benzene] at rates of 0.4 and 0.12 kg a.i. ha(-1), respectively, to investigate their effect on the growth and activities of phosphate solubilizing microorganisms in relation to availability of phosphorus as well as persistence of the herbicides in the rhizosphere soil of wetland rice (Oryza sativa L. variety IR-36). Application of herbicides stimulated the population and activities of phosphate solubilizing microorganisms and also the availability of phosphorus in the rhizosphere soil. Oxyfluorfen provided greater microbial stimulation than oxadiazon. Dissipation of oxyfluorfen and oxadiazon followed first order reaction kinetics with half-life (T(1/2)) of 8.8 and 12 days, respectively. Sixty days after application 0.5% and 3% of the applied oxadiazon and oxyfluorfen residues persisted, respectively, in the rhizosphere soil of rice.
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NASA Astrophysics Data System (ADS)
Asal, Eren Karsu; Polymeris, George S.; Gultekin, Serdar; Kitis, George
2018-06-01
Thermoluminescence (TL) techniques are very useful in the research of the persistent Luminescence (PL) phosphors research. It gives information about the existence of energy levels within the forbidden band, its activation energy, kinetic order, lifetime etc. The TL glow curve of Sr4Al14O25 :Eu2+,Dy3+ persistent phosphor, consists of two well separated glow peaks. The TL techniques used to evaluate activation energy were the initial rise, prompt isothermal decay (PID) of TL of each peak at elevated temperatures and the glow - curve fitting. The behavior of the PID curves of the two peak is very different. According to the results of the PID procedure and the subsequent data analysis it is suggested that the mechanism behind the low temperature peak is a delocalized transition. On the other hand the mechanism behind the high temperature peak is localized transition involving a tunneling recombination between electron trap and luminescence center.
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Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine
2015-01-01
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways. PMID:26402858
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Sipliviy, V A; Yevtushenko, D V; Naumova, O V; Andreyeshchev, S A; Yevtushenko, A V
2016-02-01
Abstract The results of surgical treatment of 184 patients for obturation jaundice, caused by choledocholithiasis, were analyzed. Morphological changes of the liver were studied in 20 patients. There were three groups of patients delineated, depending on the obturation jaundice duration: up to 7 days, from 8 to 14 days, more than 15 days, and also a group of patients after the bile outflow restoration. The obturation jaundice occurrence in choledocholithiasis is accompanied by significant morphological changes in the liver, severity of which is enhancing while the obturation jaundice persistence increasing. While persistence of obturation jaundice through 8 days and more the connective tissue volume is enhancing, a relative volume of hepatocytes is reducing and a stromal-parenchymatous index is increasing. The bile outflow restoration secures significant reduction of intensity of alterative and inflammatory changes in hepatic parenchyma, as well as activation of reparative processes in the tissue. In cholangitis, caused by P. aeruginosa and E. coli, according to morphological investigations data, in the liver a diffuse purulent cholangitis on background of chronic changes in accordance to duration of the obturation jaundice persists.
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Takai, Kazuya; Suzuki, Toshio; Kawazu, Kazuyoshi
2004-01-01
In an earlier paper the authors reported the creation of a novel emamectin benzoate 40 g litre(-1) liquid formulation (Shot Wan Liquid Formulation). The injection of this formulation exerted a preventative effect against the pine wilt disease caused by the pine wood nematode, Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle, and this effect lasted for at least 3 years. The present study was carried out to show experimentally that the marked effect of this formulation was due to the presence and persistence in pine tissues of sufficient amounts of emamectin benzoate to inhibit nematode propagation. A cleanup procedure prior to quantitative analysis of emamectin benzoate by fluorescence HPLC was devised. The presence of the compound in concentrations sufficient to inhibit nematode propagation in the shoots of current growth and its persistence for 3 years explained the marked preventative effect. Non-distribution of emamectin benzoate in some parts of the lower trunk suggested that the formulation should be injected at several points for large trees in order to distribute the compound uniformly to lower branches.
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Ling, Binhua; Mohan, Mahesh; Lackner, Andrew A; Green, Linda C; Marx, Preston A; Doyle, Lara A; Veazey, Ronald S
2010-12-15
Although patients with human immunodeficiency virus type 1 infection who are receiving antiretroviral therapy and those with long-term, nonprogressive infection (LTNPs) usually have undetectable viremia, virus persists in tissue reservoirs throughout infection. However, the distribution and magnitude of viral persistence and replication in tissues has not been adequately examined. Here, we used the simian immunodeficiency virus (SIV) macaque model to quantify and compare viral RNA and DNA in the small (jejunum) and large (colon) intestine of LTNPs. In LTNPs with chronic infection, the colon had consistently higher viral levels than did the jejunum. The colon also had higher percentages of viral target cells (memory CD4(+) CCR5(+) T cells) and proliferating memory CD4(+) T cells than did the jejunum, whereas markers of cell activation were comparable in both compartments. These data indicate that the large intestine is a major viral reservoir in LTNPs, which may be the result of persistent, latently infected cells and higher turnover of naive and central memory CD4(+) T cells in this major immunologic compartment.
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Host Cell Invasion by Trypanosoma cruzi: A Unique Strategy that Promotes Persistence
Fernandes, Maria Cecilia; Andrews, Norma W.
2012-01-01
The intracellular protozoan parasite Trypanosoma cruzi is the causative agent of Chagas' disease, a serious disorder that affects millions of people in Latin America. Despite the development of life-long immunity following infections, the immune system fails to completely clear the parasites, which persist for decades within host tissues. Cardiomyopathy is one of the most serious clinical manifestations of the disease, and a major cause of sudden death in endemic areas. Despite decades of study, there is still debate about the apparent preferential tropism of the parasites for cardiac muscle, and its role in the pathology of the disease. In this review we discuss these issues in the light of recent observations, which indicate that T. cruzi invades host cells by subverting a highly conserved cellular pathway for the repair of plasma membrane lesions. Plasma membrane injury and repair is particularly prevalent in muscle cells, suggesting that the mechanism used by the parasites for cell invasion may be a primary determinant of tissue tropism, intracellular persistence, and Chagas' disease pathology. PMID:22339763
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Contraction kinetics of ventricular muscle from hibernating and nonhibernating mammals.
NASA Technical Reports Server (NTRS)
South, F. E.; Jacobs, H. K.
1973-01-01
Temperature-dependent studies of excitability and tension-production kinetics were made on isolated trabecular strips from hibernating hamsters (HH), nonhibernating hamsters (CH), and from rats (R). The strips were electrically driven and isometric tension along with its first time derivative (dP/dt) were recorded. Excitabilities of both hamster tissues were greater than that of rat tissue from 5 to 38 C with HH greater than CH. Peak tension production followed the order of HH greater than CH greater than R at all temperatures below 24 C. Rat preparations showed an optimum peak tension production at about 31 C while HH and CH showed optima between 17 and 24 C. Times to maximal rates of tension rise showed significant variation. In this respect, the order of sensitivity to decreasing temperature was HH greater than CH greater than R.
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NASA Technical Reports Server (NTRS)
Carra, Claudio; Wang, Minli; Huff, Janice L.; Hada, Megumi; ONeill, Peter; Cucinotta, Francis A.
2010-01-01
Signal transduction controls cellular and tissue responses to radiation. Transforming growth factor beta (TGFbeta) is an important regulator of cell growth and differentiation and tissue homeostasis, and is often dis-regulated in tumor formation. Mathematical models of signal transduction pathways can be used to elucidate how signal transduction varies with radiation quality, and dose and dose-rate. Furthermore, modeling of tissue specific responses can be considered through mechanistic based modeling. We developed a mathematical model of the negative feedback regulation by Smad7 in TGFbeta-Smad signaling and are exploring possible connections to the WNT/beta -catenin, and ATM/ATF2 signaling pathways. A pathway model of TGFbeta-Smad signaling that includes Smad7 kinetics based on data in the scientific literature is described. Kinetic terms included are TGFbeta/Smad transcriptional regulation of Smad7 through the Smad3-Smad4 complex, Smad7-Smurf1 translocation from nucleus to cytoplasm, and Smad7 negative feedback regulation of the TGFO receptor through direct binding to the TGFO receptor complex. The negative feedback controls operating in this pathway suggests non-linear responses in signal transduction, which are described mathematically. We then explored possibilities for cross-talk mediated by Smad7 between DNA damage responses mediated by ATM, and with the WNT pathway and consider the design of experiments to test model driven hypothesis. Numerical comparisons of the mathematical model to experiments and representative predictions are described.
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Improved correction for the tissue fraction effect in lung PET/CT imaging
NASA Astrophysics Data System (ADS)
Holman, Beverley F.; Cuplov, Vesna; Millner, Lynn; Hutton, Brian F.; Maher, Toby M.; Groves, Ashley M.; Thielemans, Kris
2015-09-01
Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences reconstructed image values and that it is vital to correct for this ‘tissue fraction effect’ (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K1 and Ki along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34-80% in the best case and 29-96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted.
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Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework
NASA Technical Reports Server (NTRS)
Hu, Shaowen; Cucinotta, Francis A.
2013-01-01
The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.
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Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bagby, G.J.; Corll, C.B.; Martinez, R.R.
1987-07-01
Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionallymore » hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.« less
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Side-binding proteins modulate actin filament dynamics
Crevenna, Alvaro H; Arciniega, Marcelino; Dupont, Aurélie; Mizuno, Naoko; Kowalska, Kaja; Lange, Oliver F; Wedlich-Söldner, Roland; Lamb, Don C
2015-01-01
Actin filament dynamics govern many key physiological processes from cell motility to tissue morphogenesis. A central feature of actin dynamics is the capacity of filaments to polymerize and depolymerize at their ends in response to cellular conditions. It is currently thought that filament kinetics can be described by a single rate constant for each end. In this study, using direct visualization of single actin filament elongation, we show that actin polymerization kinetics at both filament ends are strongly influenced by the binding of proteins to the lateral filament surface. We also show that the pointed-end has a non-elongating state that dominates the observed filament kinetic asymmetry. Estimates of flexibility as well as effects on fragmentation and growth suggest that the observed kinetic diversity arises from structural alteration. Tuning elongation kinetics by exploiting the malleability of the filament structure may be a ubiquitous mechanism to generate a rich variety of cellular actin dynamics. DOI: http://dx.doi.org/10.7554/eLife.04599.001 PMID:25706231
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Zhang, Long; Vogel, Yan Boris; Noble, Benjamin B; Gonçales, Vinicius R; Darwish, Nadim; Brun, Anton Le; Gooding, J Justin; Wallace, Gordon G; Coote, Michelle L; Ciampi, Simone
2016-08-03
This work demonstrates the effect of electrostatic interactions on the electroactivity of a persistent organic free radical. This was achieved by chemisorption of molecules of 4-azido-2,2,6,6-tetramethyl-1-piperdinyloxy (4-azido-TEMPO) onto monolayer-modified Si(100) electrodes using a two-step chemical procedure to preserve the open-shell state and hence the electroactivity of the nitroxide radical. Kinetic and thermodynamic parameters for the surface electrochemical reaction are investigated experimentally and analyzed with the aid of electrochemical digital simulations and quantum-chemical calculations of a theoretical model of the tethered TEMPO system. Interactions between the electrolyte anions and the TEMPO grafted on highly doped, i.e., metallic, electrodes can be tuned to predictably manipulate the oxidizing power of surface nitroxide/oxoammonium redox couple, hence showing the practical importance of the electrostatics on the electrolyte side of the radical monolayer. Conversely, for monolayers prepared on the poorly doped electrodes, the electrostatic interactions between the tethered TEMPO units and the semiconductor-side, i.e., space-charge, become dominant and result in drastic kinetic changes to the electroactivity of the radical monolayer as well as electrochemical nonidealities that can be explained as an increase in the self-interaction "a" parameter that leads to the Frumkin isotherm.
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Sciarra, Alessandro; Maggi, Martina; Fasulo, Andrea; Salciccia, Stefano; Gentile, Vincenzo; Cattarino, Susanna; Gentilucci, Alessandro
2017-08-01
The aim of this study was to analyze the significance of an increase in total prostate-specific antigen (PSA) serum levels despite dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We focused our attention on the rate of the first PSA increase and on the influence of prostatic inflammation. From 2011 to 2016, 365 men with a previous negative prostate biopsy and persistent elevated PSA levels received dutasteride treatment. The population was followed for a range of 12-48 months. One hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir value during the follow-up were included in Group A and underwent a new prostate biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in 66% of cases. The percentage of PSA reduction after 6 months of treatment was not a significant indicator of the risk for PC. The distribution of inflammatory infiltrates significantly (p<00.01) varied from positive to negative prostate biopsies. The relative risk for PC at biopsy significantly increased according to PSA level during dutasteride. Treatment with dutasteride can help to analyze PSA kinetic. A persistent prostatic inflammation is a factor able to reduce the performance of PSA kinetic during dutasteride treatment.
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Qian, Zuoming; Covarrubias, Andrés; Grindal, Alexander W; Akens, Margarete K; Lilge, Lothar; Marjoribanks, Robin S
2016-06-01
High-repetition-rate burst-mode ultrafast-laser ablation and disruption of biological tissues depends on interaction of each pulse with the sample, but under those particular conditions which persist from previous pulses. This work characterizes and compares the dynamics of absorption and scattering of a 133-MHz repetition-rate, burst-mode ultrafast-pulse laser, in agar hydrogel targets and distilled water. The differences in energy partition are quantified, pulse-by-pulse, using a time-resolving integrating-sphere-based device. These measurements reveal that high-repetition-rate burst-mode ultrafast-laser ablation is a highly dynamical process affected by the persistence of ionization, dissipation of plasma plume, neutral material flow, tissue tensile strength, and the hydrodynamic oscillation of cavitation bubbles.
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Rapid activation of the interferon system in vivo.
Dianzani, F; Gullino, P; Baron, S
1978-01-01
Experiments were carried out to study the kinetics of local interferon production in the subcutaneous tissues of rats stimulated with Newcastle disease virus. Specifically, the interferon produced and released in the extracellular fluids was collected at various intervals of time in micropore chambers implanted into the subcutaneous tissue of rats. Interferon was detected at moderate titers 1 h after induction, and it was present at high titer at 2 h. The interferon levels remained remarkably high in the samples collected after 3, 5, and 24 h, and in some rats it was still detectable after 48 and 72 h. Since control experiments showed that it requires 2 to 3 h for interferon to penetrate the chambers, it may be concluded that high concentrations of interferon are present in the extracellular fluid within 1 h of induction. The evaluation of the kinetics of production and of the concentrations attained in the extracellular fluid suggests that in a solid tissue a cell infected by a potent interferon inducer may produce interferon early enough and in sufficient quantity to protect neighboring cells before the production of progeny virions. PMID:669799
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Hadi, M.F.; Sander, E.A.; Ruberti, J.W.; Barocas, V. H.
2011-01-01
Recent work has demonstrated that enzymatic degradation of collagen fibers exhibits strain-dependent kinetics. Conceptualizing how the strain dependence affects remodeling of collagenous tissues is vital to our understanding of collagen management in native and bioengineered tissues. As a first step towards this goal, the current study puts forward a multiscale model for enzymatic degradation and remodeling of collagen networks for two sample geometries we routinely use in experiments as model tissues. The multiscale model, driven by microstructural data from an enzymatic decay experiment, includes an exponential strain-dependent kinetic relation for degradation and constant growth. For a dogbone sample under uniaxial load, the model predicted that the distribution of fiber diameters would spread over the course of degradation because of variation in individual fiber load. In a cross-shaped sample, the central region, which experiences smaller, more isotropic loads, showed more decay and less spread in fiber diameter compared to the arms. There was also a slight shift in average orientation in different regions of the cruciform. PMID:22180691
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Ton Nu, Phuong Anh; Rappelli, Paola; Dessì, Daniele; Nguyen, Vu Quoc Huy; Fiori, Pier Luigi
2015-12-01
Persistence of antibodies against pathogens after antimicrobial treatment is a marker of therapy failure or evolution to a chronic infection. The kinetics of antibody production decrease following antigen elimination is highly variable, and predicting the duration of soluble immunity in infectious diseases is often impossible. This hampers the development and use of immunoassays for diagnostic and seroepidemiological purposes. In the case of Trichomonas vaginalis infection, the kinetics of antibody levels decrease following therapy has never been studied. We thus investigated the clearance of circulating anti-T. vaginalis IgGs after pharmacological treatment in patients affected by trichomoniasis. 18 female patients affected by acute trichomoniasis were enrolled in this study. After metronidazole therapy administration, subjects were followed up monthly up to 5 months, and serum levels of anti-T. vaginalis IgGs were measured by ELISA. We showed that a successful therapy is characterised by a relatively fast decline of specific antibodies, until turning into negative by ELISA in 1-3 months. In a few patients we observed that the persistence of anti-T. vaginalis antibodies was associated with an evolution to chronic infection, which may be due to treatment failure or to reinfection by untreated sexual partners. Our results describe the direct correlation between the decline of a specific humoral anti-T. vaginalis response and an effective antimicrobial therapy. These findings may facilitate the follow-up approach to circumvent limitations in developing new diagnostic tools and techniques routinely used in microbiology laboratories to assess the presence of T. vaginalis in clinical samples. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Synthetic (p)ppGpp Analogue Is an Inhibitor of Stringent Response in Mycobacteria
Syal, Kirtimaan; Flentie, Kelly; Bhardwaj, Neerupma; Maiti, Krishnagopal; Jayaraman, Narayanaswamy; Stallings, Christina L.
2017-01-01
ABSTRACT Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by RelMsm in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis, where inhibition in each case was observed. In vivo, (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis. The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry. PMID:28396544
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Synthetic (p)ppGpp Analogue Is an Inhibitor of Stringent Response in Mycobacteria.
Syal, Kirtimaan; Flentie, Kelly; Bhardwaj, Neerupma; Maiti, Krishnagopal; Jayaraman, Narayanaswamy; Stallings, Christina L; Chatterji, Dipankar
2017-06-01
Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by Rel Msm in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis , where inhibition in each case was observed. In vivo , (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry. Copyright © 2017 American Society for Microbiology.
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Nagaraja, Sridevi; Reifman, Jaques; Mitrophanov, Alexander Y.
2015-01-01
Timely resolution of inflammation is critical for the restoration of homeostasis in injured or infected tissue. Chronic inflammation is often characterized by a persistent increase in the concentrations of inflammatory cells and molecular mediators, whose distinct amount and timing characteristics offer an opportunity to identify effective therapeutic regulatory targets. Here, we used our recently developed computational model of local inflammation to identify potential targets for molecular interventions and to investigate the effects of individual and combined inhibition of such targets. This was accomplished via the development and application of computational strategies involving the simulation and analysis of thousands of inflammatory scenarios. We found that modulation of macrophage influx and efflux is an effective potential strategy to regulate the amount of inflammatory cells and molecular mediators in both normal and chronic inflammatory scenarios. We identified three molecular mediators − tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and the chemokine CXCL8 − as potential molecular targets whose individual or combined inhibition may robustly regulate both the amount and timing properties of the kinetic trajectories for neutrophils and macrophages in chronic inflammation. Modulation of macrophage flux, as well as of the abundance of TNF-α, TGF-β, and CXCL8, may improve the resolution of chronic inflammation. PMID:26633296
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Differences in fate, behavior and uptake of conventional- and nano-pesticides
NASA Astrophysics Data System (ADS)
Anuar, M. Firdaus Mohd; E Hodson, Mark; Boxall, Alistair BA
2017-04-01
Nanopesticides, in which conventional pesticides are designed into nanoparticles, are now available and are marketed as having improved longevity and efficacy in the environment. Nanoparticles are known to have different properties to dissolved chemicals and as such it is possible that the fate and behaviour of nanopesticides differs from conventional pesticides. We present work on the synthetic pyrethroid bifenthrin to explore the implications of nanoencapsulation for the sorption, persistence and uptake of the active ingredient in soil-earthworm systems. Studies were done using the active ingredient, a traditional formulation and two nanoformulations. In adsorption experiments conducted using five soils with a range of properties (pH 4.7 - 7.7; % organic carbon 1.2 - 5.2; texture silt loam to loamy sand), adsorption was well described by linear isotherms. Adsorption of analytical grade bifenthrin (Kd = 1800 - 7200 mL / g) was greater than that of a commercial formulation (Kd = 190 - 470 mL / g) which in turn was greater than that of nanoformulations (Kd = 52 - 150 mL / g). For all bifenthrin types adsorption increased with increasing soil organic matter content. Degradation rates of the analytical grade bifenthrin and commercial formulation were similar and faster than those of nanoformulations. Degradation rates were faster in non-sterile compared to sterile conditions. These results suggest that nano-encapsulation could lead to increased mobility and persistence of bifenthrin in the environment and therefore potentially increased exposure and bioavailability. To investigate the effects of nanoencapsulation on uptake we carried out a series of uptake and excretion experiments using the earthworms Eisenia fetida and Lumbricus terrestris. Over the exposure period the concentration of bifenthrin in the soil decreased and increased in the earthworms. Rates of accumulation and excretion were greater for the nanobifenthrin than the non-nanoformulation and active ingredient. Dissection and analysis of earthworm tissues indicated that the accumulated bifenthrin from the nano exposure was concentrated in the earthworm gut whereas the accumulated bifenthrin in the conventional exposure was concentrated in the earthworm tissues. We used kinetic modelling to determine bioconcentration factors. The higher accumulation and excretion rates result in predicted lower bioconcentration factors for the nanobofenthrin compared to the conventional and analytical grade forms. Our experiments demonstrate the differing behaviours of a conventional and nano-formluated pesticide therefore suggesting that current environmental risk assessment methodologies for conventional pesticides may not be appropriate for nanoformulations.
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Coxiella burnetii shedding by dairy cows.
Guatteo, Raphaël; Beaudeau, François; Joly, Alain; Seegers, Henri
2007-01-01
While shedding routes of Coxiella burnetii are identified, the characteristics of Coxiella shedding are still widely unknown, especially in dairy cattle. However, this information is crucial to assess the natural course of Coxiella burnetii infection within a herd and then to elaborate strategies to limit the risks of transmission between animals and to humans. The present study aimed at (i) describing the characteristics of Coxiella burnetii shedding by dairy cows (in milk, vaginal mucus, faeces) in five infected dairy herds, and at (ii) investigating the possible relationships between shedding patterns and serological responses. A total of 145 cows were included in a follow-up consisting of seven concomitant samplings of milk, vaginal mucus, faeces and blood (Day 0, D7, D14, D21, D28, D63, D90). Detection and quantification of Coxiella burnetii titres were performed in milk, vaginal mucus and faeces samples using real-time PCR assay, while antibodies against Coxiella were detected using an ELISA technique. For a given shedding route, and a given periodicity (weekly or monthly), cows were gathered into different shedding kinetic patterns according to the sequence of PCR responses. Distribution of estimated titres in Coxiella burnetii was described according to shedding kinetic patterns. Coxiella burnetii shedding was found scarcely and sporadically in faeces. Vaginal mucus shedding concerned almost 50% of the cows studied and was found intermittently or sporadically, depending on the periodicity considered. Almost 40% of cows were detected as milk shedders, with two predominant shedding patterns: persistent and sporadic, regardless of the sampling periodicity. Significantly higher estimated titres in Coxiella burnetii were observed in cows with persistent shedding patterns suggesting the existence of heavy shedder cows. These latter cows were mostly, persistently highly-seropositive, suggesting that repeated serological testings could be a reliable tool to screen heavy shedders, before using PCR assays.
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Hemoglobin Kinetics and Long-term Prognosis in Heart Failure.
Díez-López, Carles; Lupón, Josep; de Antonio, Marta; Zamora, Elisabet; Domingo, Mar; Santesmases, Javier; Troya, Maria-Isabel; Boldó, Maria; Bayes-Genis, Antoni
2016-09-01
The influence of hemoglobin kinetics on outcomes in heart failure has been incompletely established. Hemoglobin was determined at the first visit and at 6 months. Anemia was defined according to World Health Organization criteria (hemoglobin < 13g/dL for men and hemoglobin < 12g/dL for women). Patients were classified relative to their hemoglobin values as nonanemic (both measurements normal), transiently anemic (anemic at the first visit but not at 6 months), newly anemic (nonanemic initially but anemic at 6 months), or permanently anemic (anemic in both measurements). A total of 1173 consecutive patients (71.9% men, mean age 66.8±12.2 years) were included in the study. In all, 476 patients (40.6%) were considered nonanemic, 170 (14.5%) had transient anemia, 147 (12.5%) developed new-onset anemia, and 380 (32.4%) were persistently anemic. During a follow-up of 3.7±2.8 years after the 6-month visit, 494 patients died. On comprehensive multivariable analyses, anemia (P < .001) and the type of anemia (P < .001) remained as independent predictors of all-cause mortality. Compared with patients without anemia, patients with persistent anemia (hazard ratio [HR] = 1.62; 95% confidence interval [95%CI], 1.30-2.03; P < .001) and new-onset anemia (HR = 1.39; 95%CI, 1.04-1.87, P = .03) had higher mortality, and even transient anemia showed a similar trend, although without reaching statistical significance (HR = 1.31; 95%CI, 0.97-1.77, P = .075). Anemia, especially persistent and of new-onset, and to a lesser degree, transient anemia, is deleterious in heart failure. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
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Comparison of Kinetic Models for Dual-Tracer Receptor Concentration Imaging in Tumors
Hamzei, Nazanin; Samkoe, Kimberley S; Elliott, Jonathan T; Holt, Robert W; Gunn, Jason R; Hasan, Tayyaba; Pogue, Brian W; Tichauer, Kenneth M
2014-01-01
Molecular differences between cancerous and healthy tissue have become key targets for novel therapeutics specific to tumor receptors. However, cancer cell receptor expression can vary within and amongst different tumors, making strategies that can quantify receptor concentration in vivo critical for the progression of targeted therapies. Recently a dual-tracer imaging approach capable of providing quantitative measures of receptor concentration in vivo was developed. It relies on the simultaneous injection and imaging of receptor-targeted tracer and an untargeted tracer (to account for non-specific uptake of the targeted tracer). Early implementations of this approach have been structured on existing “reference tissue” imaging methods that have not been optimized for or validated in dual-tracer imaging. Using simulations and mouse tumor model experimental data, the salient findings in this study were that all widely used reference tissue kinetic models can be used for dual-tracer imaging, with the linearized simplified reference tissue model offering a good balance of accuracy and computational efficiency. Moreover, an alternate version of the full two-compartment reference tissue model can be employed accurately by assuming that the K1s of the targeted and untargeted tracers are similar to avoid assuming an instantaneous equilibrium between bound and free states (made by all other models). PMID:25414912
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Shi, Meng; Kretlow, James D.; Spicer, Patrick P.; Tabata, Yasuhiko; Demian, Nagi; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.
2011-01-01
An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous polymethylmethacrylate (PMMA) constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8–38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 µg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct. PMID:21295086
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Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.
2012-01-01
Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.
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Pestrak, Matthew J; Chaney, Sarah B; Eggleston, Heather C; Dellos-Nolan, Sheri; Dixit, Sriteja; Mathew-Steiner, Shomita S; Roy, Sashwati; Parsek, Matthew R; Sen, Chandan K; Wozniak, Daniel J
2018-02-01
Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. aeruginosa infections become incredibly difficult to treat due to the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant of P. aeruginosa, known as a rugose small-colony variant (RSCV), is frequently isolated from chronic infections and is correlated with poor clinical outcome. The development of these mutants during infection suggests a selective advantage for this phenotype, but it remains unclear how this phenotype promotes persistence. While prior studies suggest RSCVs could survive by evading the host immune response, our study reveals infection with the RSCV, PAO1ΔwspF, stimulated an extensive inflammatory response that caused significant damage to the surrounding host tissue. In both a chronic wound model and acute pulmonary model of infection, we observed increased bacterial burden, host tissue damage, and a robust neutrophil response during RSCV infection. Given the essential role of neutrophils in P. aeruginosa-mediated disease, we investigated the impact of the RSCV phenotype on neutrophil function. The RSCV phenotype promoted phagocytic evasion and stimulated neutrophil reactive oxygen species (ROS) production. We also demonstrate that bacterial aggregation and TLR-mediated pro-inflammatory cytokine production contribute to the immune response to RSCVs. Additionally, RSCVs exhibited enhanced tolerance to neutrophil-produced antimicrobials including H2O2 and the antimicrobial peptide LL-37. Collectively, these data indicate RSCVs elicit a robust but ineffective neutrophil response that causes significant host tissue damage. This study provides new insight on RSCV persistence, and indicates this variant may have a critical role in the recurring tissue damage often associated with chronic infections.
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Khoshnevis, Sepideh; Craik, Natalie K.
2015-01-01
Purpose Localized cooling is widely used in treating soft tissue injuries by modulating swelling, pain, and inflammation. One of the primary outcomes of localized cooling is vasoconstriction within the underlying skin. It is thought that in some instances, cryotherapy may be causative of tissue necrosis and neuropathy via cold-induced ischaemia leading to nonfreezing cold injury (NFCI). The purpose of this study is to quantify the magnitude and persistence of vasoconstriction associated with cryotherapy. Methods Data are presented from testing with four different FDA approved cryotherapy devices. Blood perfusion and skin temperature were measured at multiple anatomical sites during baseline, active cooling, and passive rewarming periods. Results Local cutaneous blood perfusion was depressed in response to cooling the skin surface with all devices, including the DonJoy (DJO, p = 2.6 × 10−8), Polar Care 300 (PC300, p = 1.1 × 10−3), Polar Care 500 Lite (PC500L, p = 0.010), and DeRoyal T505 (DR505, p = 0.016). During the rewarming period, parasitic heat gain from the underlying tissues and the environment resulted in increased temperatures of the skin and pad for all devices, but blood perfusion did not change significantly, DJO (n.s.), PC300 (n.s.), PC500L (n.s.), and DR505 (n.s.). Conclusions The results demonstrate that cryotherapy can create a deep state of vasoconstriction in the local area of treatment. In the absence of independent stimulation, the condition of reduced blood flow persists long after cooling is stopped and local temperatures have rewarmed towards the normal range, indicating that the maintenance of vasoconstriction is not directly dependent on the continuing existence of a cold state. The depressed blood flow may dispose tissue to NFCI. PMID:24562697
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Stenfeldt, C; Pacheco, J M; Smoliga, G R; Bishop, E; Pauszek, S J; Hartwig, E J; Rodriguez, L L; Arzt, J
2016-04-01
A systematic study was performed to investigate the potential of pigs to establish and maintain persistent foot-and-mouth disease virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal fluids obtained after resolution of clinical infection with any of five FMDV strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of live virus from tissue samples harvested at 28-100 days post-infection from convalescent pigs recovered from clinical or subclinical FMD. Despite lack of detection of infectious FMDV, there was a high prevalence of FMDV RNA detection in lymph nodes draining lesion sites harvested at 35 days post-infection, with the most frequent detection recorded in popliteal lymph nodes (positive detection in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV capsid antigen was localized within follicles of draining lymph nodes, but without concurrent detection of FMDV non-structural protein. There was a marked decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and no antigen or viral RNA could be detected in samples obtained at 100 dpi. The data presented herein provide the most extensive investigation of FMDV persistence in pigs. The overall conclusion is that domestic pigs are unlikely to be competent long-term carriers of infectious FMDV; however, transient persistence of FMDV protein and RNA in lymphoid tissues is common following clinical or subclinical infection. © Published 2014. This article is a US Government work and is in the public domain in the USA.
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Khoshnevis, Sepideh; Craik, Natalie K; Diller, Kenneth R
2015-09-01
Localized cooling is widely used in treating soft tissue injuries by modulating swelling, pain, and inflammation. One of the primary outcomes of localized cooling is vasoconstriction within the underlying skin. It is thought that in some instances, cryotherapy may be causative of tissue necrosis and neuropathy via cold-induced ischaemia leading to nonfreezing cold injury (NFCI). The purpose of this study is to quantify the magnitude and persistence of vasoconstriction associated with cryotherapy. Data are presented from testing with four different FDA approved cryotherapy devices. Blood perfusion and skin temperature were measured at multiple anatomical sites during baseline, active cooling, and passive rewarming periods. Local cutaneous blood perfusion was depressed in response to cooling the skin surface with all devices, including the DonJoy (DJO, p = 2.6 × 10(-8)), Polar Care 300 (PC300, p = 1.1 × 10(-3)), Polar Care 500 Lite (PC500L, p = 0.010), and DeRoyal T505 (DR505, p = 0.016). During the rewarming period, parasitic heat gain from the underlying tissues and the environment resulted in increased temperatures of the skin and pad for all devices, but blood perfusion did not change significantly, DJO (n.s.), PC300 (n.s.), PC500L (n.s.), and DR505 (n.s.). The results demonstrate that cryotherapy can create a deep state of vasoconstriction in the local area of treatment. In the absence of independent stimulation, the condition of reduced blood flow persists long after cooling is stopped and local temperatures have rewarmed towards the normal range, indicating that the maintenance of vasoconstriction is not directly dependent on the continuing existence of a cold state. The depressed blood flow may dispose tissue to NFCI.
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Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes
Garnett, C. T.; Erdman, D.; Xu, W.; Gooding, Linda R.
2002-01-01
The common species C adenoviruses (serotypes Ad1, Ad2, Ad5, and Ad6) infect more than 80% of the human population early in life. Following primary infection, the virus can establish an asymptomatic persistent infection in which infectious virions are shed in feces for several years. The probable source of persistent virus is mucosa-associated lymphoid tissue, although the molecular details of persistence or latency of adenovirus are currently unknown. In this study, a sensitive real-time PCR assay was developed to quantitate species C adenovirus DNA in human tissues removed for routine tonsillectomy or adenoidectomy. Using this assay, species C DNA was detected in Ficoll-purified lymphocytes from 33 of 42 tissue specimens tested (79%). The levels varied from fewer than 10 to greater than 2 × 106 copies of the adenovirus genome/107 cells, depending on the donor. DNA from serotypes Ad1, Ad2, and Ad5 was detected, while the rarer serotype Ad6 was not. When analyzed as a function of donor age, the highest levels of adenovirus genomes were found among the youngest donors. Antibody-coated magnetic beads were used to purify lymphocytes into subpopulations and determine whether viral DNA could be enriched within any purified subpopulations. Separation of T cells (CD4/8- expressing and/or CD3-expressing cells) enriched viral DNA in each of nine donors tested. In contrast, B-cell purification (CD19-expressing cells) invariably depleted or eliminated viral DNA. Despite the frequent finding of significant quantities of adenovirus DNA in tonsil and adenoid tissues, infectious virus was rarely present, as measured by coculture with permissive cells. These findings suggest that human mucosal T lymphocytes may harbor species C adenoviruses in a quiescent, perhaps latent form. PMID:12368303
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Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy
2017-11-15
Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics.
Scandurra, Francesca M; Gnaiger, Erich
2010-01-01
When oxygen supply to tissues is limiting, mitochondrial respiration and ATP production are compromised. To assess the bioenergetic consequences under normoxia and hypoxia, quantitative evaluation of mitochondrial oxygen kinetics is required. Using high-resolution respirometry, the "apparent K (m)" for oxygen or p (50) of respiration in 32D cells was determined at 0.05 +/- 0.01 kPa (0.4 mmHg, 0.5 microM, 0.25% air saturation). Close agreement with p (50) of isolated mitochondria indicates that intracellular gradients are small in small cells at routine activity. At intracellular p (O2) <2 kPa (15 mmHg, 10% air saturation) in various tissues under normoxia, respiration is limited by >2% with a p (50) of 0.05 kPa. Over-estimation of p (50) at 0.4 kPa (3 mmHg) would imply significant (>17%) oxygen limitation of respiration under intracellular normoxia. Based on a critical review, we conclude that p (50) ranges from 0.01 to 0.10 kPa in mitochondria and small cells in the absence of inhibitors of cytochrome c oxidase, whereas experimental artefacts explain the controversial >200-fold range of p (50) in the literature on mitochondrial oxygen kinetics.
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Renuka, S; Ramanujam, B; Poornesha, B
2016-06-01
The present study was conducted to examine the ability of six promising indigenous isolates of Beauveria bassiana (NBAII-Bb-5a, 7, 14, 19, 23 and 45) as an endophyte in maize stem and leaf tissues. Maize seedlings (var. Nithyashree) were inoculated with conidial suspensions and were examined for endophytic establishment in leaf and stems at different intervals during 15-90 days after treatment. All six isolates showed colonization in stem and leaf tissues with varying abilities of colonization and persistence. The mean percent colonization ranged from 7.41 to 20.37 % in older stem tissues and 3.70 to 21.29 % in young stem tissues and in leaf, it ranged from 6.46 to 27.78 % in older leaf tissues and 11.11 to 26.85 % in young leaf tissues. Among six isolates tested, Bb-23 isolate recorded the maximum mean colonization in older stem (20.37 %), older leaf (27.78 %) and in young stem (21.29 %). Bb-5a isolate showed maximum mean colonization in young leaf tissues (26.85 %). Persistence of inoculated fungal isolates decreased with increase in age of the plant. No physical symptoms of damage were observed in any of the B. bassiana treated plants. No colonization of B. bassiana was observed in the untreated control maize plants. The results obtained in plating and PCR techniques were similar with regard to the confirmation of endophytic establishment of B. bassiana. This study indicated the possibility of using B. bassiana as an endophyte in maize for management of maize stem borer, Chilo partellus.
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Cell proliferation in normal epidermis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weinstein, G.D.; McCullough, J.L.; Ross, P.
1984-06-01
A detailed examination of cell proliferation kinetics in normal human epidermis is presented. Using tritiated thymidine with autoradiographic techniques, proliferative and differentiated cell kinetics are defined and interrelated. The proliferative compartment of normal epidermis has a cell cycle duration (Tc) of 311 h derived from 3 components: the germinative labeling index (LI), the duration of DNA synthesis (ts), and the growth fraction (GF). The germinative LI is 2.7% +/- 1.2 and ts is 14 h, the latter obtained from a composite fraction of labeled mitoses curve obtained from 11 normal subjects. The GF obtained from the literature and from humanmore » skin xenografts to nude mice is estimated to be 60%. Normal-appearing epidermis from patients with psoriasis appears to have a higher proliferation rate. The mean LI is 4.2% +/- 0.9, approximately 50% greater than in normal epidermis. Absolute cell kinetic values for this tissue, however, cannot yet be calculated for lack of other information on ts and GF. A kinetic model for epidermal cell renewal in normal epidermis is described that interrelates the rate of birth/entry, transit, and/or loss of keratinocytes in the 3 epidermal compartments: proliferative, viable differentiated (stratum malpighii), and stratum corneum. Expected kinetic homeostasis in the epidermis is confirmed by the very similar ''turnover'' rates in each of the compartments that are, respectively, 1246, 1417, and 1490 cells/day/mm2 surface area. The mean epidermal turnover time of the entire tissue is 39 days. The Tc of 311 h in normal cells in 8-fold longer than the psoriatic Tc of 36 h and is necessary for understanding the hyperproliferative pathophysiologic process in psoriasis.« less
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Milani-Nejad, Nima; Canan, Benjamin D; Elnakish, Mohammad T; Davis, Jonathan P; Chung, Jae-Hoon; Fedorov, Vadim V; Binkley, Philip F; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L
2015-12-15
Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization (P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients. Copyright © 2015 the American Physiological Society.
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Moses, Katrin; Klein, Johanna C; Männ, Linda; Klingberg, Anika; Gunzer, Matthias; Brandau, Sven
2016-06-01
Expansion of Ly-6G(+) myeloid cells has been reported in most murine cancer models. However, divergent findings exist regarding the role and effect of these cells on host immunity and tumor progression. Antibody-mediated depletion of Ly-6G(+) cells is a common technique to assess the in vivo relevance of these cells. Interpretation of results crucially depends on the efficacy and course of depletion. We established murine head and neck cancer models and analyzed the efficacy of antibody-mediated depletion by flow cytometry, conventional histology, and intravital imaging with a novel Ly-6G-transgenic mouse model. The first phase of depletion was characterized by effective elimination of Ly-6G(+) cells from the peripheral blood. Nevertheless, viable, resistant cells were found to reside in the tumor tissue and spleen. This peripheral depletion phase was associated with high systemic levels of granulocyte colony-stimulating factor and KC and enhanced splenic production of Ly-6G(+) cells. Even under sustained treatment with either αGr-1 or αLy-6G antibodies, peripheral blood depletion ended after approximately 1 wk and was followed by reappearance of immature Ly-6G(+) cells with an immunoregulatory phenotype. Reappearance of these depletion-resistant immature cells was enhanced in tumor-bearing, compared with naïve, control mice. Collectively, our data suggest that depletion of Ly-6G(+) myeloid cells in tumor-bearing mice is counteracted by the persistence of intratumoral cells, enhanced extramedullary granulopoiesis, and accelerated reappearance of immature cells. Hence, extensive monitoring of in vivo kinetics and tissue distribution of Ly-6G(+) cells is required in depletion studies. © Society for Leukocyte Biology.
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Persistent infection with ebola virus under conditions of partial immunity.
Gupta, Manisha; Mahanty, Siddhartha; Greer, Patricia; Towner, Jonathan S; Shieh, Wun-Ju; Zaki, Sherif R; Ahmed, Rafi; Rollin, Pierre E
2004-01-01
Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for >/==" BORDER="0">25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting that under certain conditions of immunodeficiency a host can harbor virus for prolonged periods, potentially acting as a reservoir.
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Tardieu, Didier; Bailly, Jean-Denis; Benlashehr, Imad; Auby, Alienor; Jouglar, Jean-Yves; Guerre, Philippe
2009-12-10
Toxicity and persistence of fumonisin B1 (FB1) in liver, kidney and muscle were investigated in ducks fed 5, 10 and 20mg FB1+FB2/kg feed during force-feeding. Mortality and signs of toxicity were only obtained with 20mg/kg, whereas an increased Sa/So ratio was observed from 5mg/kg on. Persistence of FB1 was only found in liver (16 and 20 microg FB1/kg liver in ducks fed 10 and 20 mg FB1+FB2/kg feed, respectively). Toxicokinetic studies were conducted by the intravenous route (IV, single dose: 10mg FB1/kg body weight) and the oral route (single dose: 100mg FB1/kg body weight), in growing ducks and in ducks during force-feeding. After IV administration, serum concentration-time curves were described by a two-compartment open model. Elimination half-life and mean residence time of FB1 were 26 and 24 min, respectively, clearance was 19.3 ml/min/kg. After oral administration, bioavailability, elimination half-life, mean residence time and clearance varied during force-feeding and growth from 2-2.3%, 71-80 min, 200-188 min, 16.7-17 ml/min/kg, respectively. Taken together these results demonstrate that the risk of persistence of FB1 in ducks after force-feeding is very low, Sa/So being a good biomarker which increases before signs of toxicity and risk of persistence of FB1 in tissue (limit of detection 13 microg/kg).
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[Distributions of H3K27me3 and its modification enzymes in different tissues of mice].
Wang, Yuying; Wang, Xinli; Zhang, Ran; Zhang, Zhiyan; Wang, Yu; Yang, Bo; Wang, Guanjie; Zhang, Xin; Ma, Fuhao; Xu, Hongye; Wu, Xiaohui; Zhang, Feng; Li, Qing
2017-11-01
Objective To investigate the levels of trimethylated histone 3 at lysine residue 27 (H3K27me3) and its modification enzymes Zeste gene enhancer homolog 2 (EZH2), lysine-specific demethylase 6B (Kdm6B/JMJD3) and lysine-specific demethylase 6A (Kdm6A/UTX) in tissues and organs of 7-day and 2-month postnatal mice. Methods Immunohistochemistry was used to detect the expressions of H3K27me3 and its modification enzymes EZH2, JMJD3 and UTX in the brain, salivary glands, back fat, thymus, lung, heart, stomach, intestines, liver, testes, and skin of 7-day and 2-month mice. Real-time quantitative PCR was used to confirm the results. The relationships between H3K27me3 and its modification enzymes were analyzed statistically. Results Immunohistochemistry showed H3K27me3 persistently present in all examined tissues of 7-day and 2-month mice. EZH2 was persistently expressed in the brain, heart, liver, and skin of 7-day and 2-month mice, but only expressed in the salivary glands, adipose tissues, thymus, lung, intestines, and testes of 2-month mice. JMJD3 was expressed in the brain, salivary glands, adipose tissues, lung, heart, stomach, intestines, testes, skin of 7-day mice, but was not expressed in the lung, adipose tissues and stomach of 2-month mice. UTX was expressed in the brain, salivary glands, adipose tissues, lung, heart, testes, skin of 7-day mice, but only expressed in the testes of 2-month mice. Most mRNA of H3K27 modification enzymes were moderately or highly expressed as their immunohistochemical results were positive. Conclusion There was H3K27me3 persistently present in the all examined tissues at different stages. EZH2 was mostly expressed in the brain, salivary glands, adipose tissues, thymus, lung, heart, intestines, liver, testes and skin of 2-month-old mice. JMJD3 and UTX were mostly expressed in the brain, salivary glands, adipose tissues, lung, heart, skin and testes of 7-day-old mice. No significant association was found between the distribution of H3K27me3 and the expression of EZH2. There was also no obvious inverse distribution relationship between H3K27me3 and JMJD3 or UTX. Moreover, there was no negative relationship between the distribution of EZH2, JMJD3 and UTX. These results suggest that EZH2, JMJD3 and UTX may play important roles in many tissues of mice after birth. The levels of H3K27me3 and its modified enzymes may be controlled by multiple factors in vivo to fulfill complex physiological functions.
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Concordant Chemical Reaction Networks
Shinar, Guy; Feinberg, Martin
2015-01-01
We describe a large class of chemical reaction networks, those endowed with a subtle structural property called concordance. We show that the class of concordant networks coincides precisely with the class of networks which, when taken with any weakly monotonic kinetics, invariably give rise to kinetic systems that are injective — a quality that, among other things, precludes the possibility of switch-like transitions between distinct positive steady states. We also provide persistence characteristics of concordant networks, instability implications of discordance, and consequences of stronger variants of concordance. Some of our results are in the spirit of recent ones by Banaji and Craciun, but here we do not require that every species suffer a degradation reaction. This is especially important in studying biochemical networks, for which it is rare to have all species degrade. PMID:22659063
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Nonclassical Kinetics of Clonal yet Heterogeneous Enzymes.
Park, Seong Jun; Song, Sanggeun; Jeong, In-Chun; Koh, Hye Ran; Kim, Ji-Hyun; Sung, Jaeyoung
2017-07-06
Enzyme-to-enzyme variation in the catalytic rate is ubiquitous among single enzymes created from the same genetic information, which persists over the lifetimes of living cells. Despite advances in single-enzyme technologies, the lack of an enzyme reaction model accounting for the heterogeneous activity of single enzymes has hindered a quantitative understanding of the nonclassical stochastic outcome of single enzyme systems. Here we present a new statistical kinetics and exactly solvable models for clonal yet heterogeneous enzymes with possibly nonergodic state dynamics and state-dependent reactivity, which enable a quantitative understanding of modern single-enzyme experimental results for the mean and fluctuation in the number of product molecules created by single enzymes. We also propose a new experimental measure of the heterogeneity and nonergodicity for a system of enzymes.
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Najera-Hernandez, Salustio; Sanchez-Alonso, Maria Patricia; Anastacio-Marcelino, Estela; Negrete-Abascal, Erasmo; Vazquez-Cruz, Candelario
2018-01-18
The draft genome sequence of Escherichia coli strain SN137 is reported here. The genome comprises 172 contigs, corresponding to 4.9 Mb with 50% G+C content, and contains several genes related to pathogenicity that explain its survival in human hematic tissue. Copyright © 2018 Najera-Hernandez et al.
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Mulon, Pierre-Yves; Achard, Damien; Babkine, Marie
2010-01-01
A 17-month-old Holstein heifer was presented for persistent enlargement above the right hind fetlock of 1-month’s duration. Diffuse plantar soft tissue swelling was present on the radiographs and ultrasonography revealed the presence of multiple porcupine quill extremities embedded in the subcutaneous tissue within the flexor tendon sheath wall. Surgical removal was performed. PMID:21037892
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Belfiore, Laurence A; Floren, Michael L; Paulino, Alexandre T; Belfiore, Carol J
2011-09-01
This research contribution addresses the mechanochemistry of intra-tissue mass transfer for nutrients, oxygen, growth factors, and other essential ingredients that anchorage-dependent cells require for successful proliferation on biocompatible surfaces. The unsteady state reaction-diffusion equation (i.e., modified diffusion equation) is solved according to the von Kármán-Pohlhausen integral method of boundary layer analysis when nutrient consumption and tissue regeneration are stimulated by harmonically imposed stress. The mass balance with diffusion and stress-sensitive kinetics represents a rare example where the Damköhler and Deborah numbers appear together in an effort to simulate the development of mass transfer boundary layers in porous viscoelastic biomaterials. The Boltzmann superposition integral is employed to calculate time-dependent strain in terms of the real and imaginary components of dynamic compliance for viscoelastic solids that transmit harmonic excitation to anchorage-dependent cells. Rates of nutrient consumption under stress-free conditions are described by third-order kinetics which include local mass densities of nutrients, oxygen, and attached cells that maintain dynamic equilibrium with active protein sites in the porous matrix. Thinner nutrient mass transfer boundary layers are stabilized at shorter dimensionless diffusion times when the stress-free intra-tissue Damköhler number increases above its initial-condition-sensitive critical value. The critical stress-sensitive intra-tissue Damköhler number, above which it is necessary to consider the effect of harmonic strain on nutrient consumption and tissue regeneration, is proportional to the Deborah number and corresponds to a larger fraction of the stress-free intra-tissue Damköhler number in rigid biomaterials. Copyright © 2011 Elsevier B.V. All rights reserved.
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Patton, Jaqunda N; Palmer, Andre F
2006-01-01
This work represents a culmination of research on oxygen transport to muscle tissue, which takes into account oxygen transport due to convection, diffusion, and the kinetics of simultaneous reactions between oxygen and hemoglobin and myoglobin. The effect of adding hemoglobin-based oxygen carriers (HBOCs) to the plasma layer of blood in a single capillary surrounded by muscle tissue based on the geometry of the Krogh tissue cylinder is examined for a range of HBOC oxygen affinity, HBOC concentration, capillary inlet oxygen tension (pO(2)), and hematocrit. The full capillary length of the hamster retractor muscle was modeled under resting (V(max) = 1.57 x 10(-4) mLO(2) mL(-1) s(-1), cell velocity (v(c)) = 0.015 cm/s) and working (V(max) = 1.57 x 10(-3) mLO(2) mL(-1) s(-1), v(c) = 0.075 cm/s) conditions. Two spacings between the red blood cell (RBC) and the capillary wall were examined, corresponding to a capillary with and without an endothelial surface layer. Simulations led to the following conclusions, which lend physiological insight into oxygen transport to muscle tissue in the presence of HBOCs: (1) The reaction kinetics between oxygen and myoglobin in the tissue region, oxygen and HBOCs in the plasma, and oxygen and RBCs in the capillary lumen should not be neglected. (2) Simulation results yielded new insight into possible mechanisms of oxygen transport in the presence of HBOCs. (3) HBOCs may act as a source or sink for oxygen in the capillary and may compete with RBCs for oxygen. (4) HBOCs return oxygen delivery to muscle tissue to normal for varying degrees of hypoxia (inlet capillary pO(2) < 30 mmHg) and anemia (hematocrit < 46%) for the hamster model.
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Analysis of tissue specific progenitor cell differentiation using FT-IR
NASA Astrophysics Data System (ADS)
Ishii, Katsunori; Kimura, Akinori; Kushibiki, Toshihiro; Awazu, Kunio
2007-07-01
Tissue specific progenitor cells and its differentiations have got a lot of attentions in regenerative medicine. The process of differentiations, the formation of tissues, has become better understood by the study using a lot of cell types progressively. These studies of cells and tissue dynamics at molecular levels are carried out through various approaches like histochemical methods, application of molecular biology and immunology. However, in case of using regenerative sources (cells, tissues and biomaterials etc.) clinically, they are measured and quality-controlled by non-contact and non-destructive methods from the view point of safety. Or the analysis with small quantities of materials could be possible if the quantities of materials are acceptable. A non-contact and non-destructive quality control method has been required. Recently, the use of Fourier Transform Infrared spectroscopy (FT-IR) has been used to monitor biochemical changes in cells, and has gained considerable importance. The changes in the cells and tissues, which are subtle and often not obvious in the histpathological studies, are shown to be well resolved using FT-IR. Moreover, although most techniques designed to detect one or a few changes, FT-IR is possible to identify the changes in the levels of various cellular biochemicals simultaneously under in vivo and in vitro conditions. The objective of this study is to establish the infrared spectroscopy of tissue specific progenitor cell differentiations as a quality control of cell sources for regenerative medicine. In the present study, as a basic study, we examine the adipose differentiation kinetics of preadipose cells (3T3-L1) and the osteoblast differentiation kinetics of mesenchymal stem cells (Kusa-A1) to analyze the infrared absorption spectra.
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Kinetic filtering of [18F]Fluorothymidine in positron emission tomography studies
NASA Astrophysics Data System (ADS)
Gray, Katherine R.; Contractor, Kaiyumars B.; Kenny, Laura M.; Al-Nahhas, Adil; Shousha, Sami; Stebbing, Justin; Wasan, Harpreet S.; Coombes, R. Charles; Aboagye, Eric O.; Turkheimer, Federico E.; Rosso, Lula
2010-02-01
[18F]Fluorothymidine (FLT) is a cell proliferation marker that undergoes predominantly hepatic metabolism and therefore shows a high level of accumulation in the liver, as well as in rapidly proliferating tumours. Furthermore, the tracer's uptake is substantial in other organs including the heart. We present a nonlinear kinetic filtering technique which enhances the visualization of tumours imaged with FLT positron emission tomography (FLT-PET). A classification algorithm to isolate cancerous tissue from healthy organs was developed and validated using 29 scan data from patients with locally advanced or metastatic breast cancer. A large reduction in signal from the liver and heart of 80% was observed following application of the kinetic filter, whilst the majority of signal from both primary tumours and metastases was retained. A scan acquisition time of 60 min has been shown to be sufficient to obtain the necessary kinetic data. The algorithm extends utility of FLT-PET imaging in oncology research.
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Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S
2014-05-01
Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection.
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Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.
2014-01-01
Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection. PMID:25364618
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Mantilla-Calderon, David
2017-01-01
ABSTRACT The presence of emerging biological pollutants in treated wastewater effluents has gained attention due to increased interest in water reuse. To evaluate the effectiveness of the removal of such contaminants by the conventional wastewater treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were assessed in microcosms of anaerobic and aerobic sludge. Results showed that E. coli PI7 decayed at a significantly lower rate under anaerobic conditions. Approximate half-lives were 32.4 ± 1.4 h and 5.9 ± 0.9 h in the anaerobic and aerobic microcosms, respectively. In the aerobic microcosms, after 72 h of operation, E. coli PI7 remained detectable, but no further decay was observed. Instead, 1 in every 10,000 E. coli cells was identified to be recalcitrant to decay and persist indefinitely in the sludge. ARGs associated with the E. coli PI7 strain were detected to have transferred to other native microorganisms in the sludge or were released to the liquid fraction upon host decay. Extracellular DNA quickly degraded in the liquid fraction of the aerobic sludge. In contrast, no DNA decay was detected in the anaerobic sludge water matrix throughout the 24-h sampling period. This study suggests an increased likelihood of environmental dispersion of ARGs associated with anaerobically treated wastewater effluents and highlights the potential importance of persister cells in the dissemination of E. coli in the environment during reuse events of treated wastewater. IMPORTANCE This study examines the decay kinetics of a pathogenic and antibiotic resistant strain of Escherichia coli in microcosms simulating biological treatment units of aerobic and anaerobic sludge. The results of this study point at a significantly prolonged persistence of the E. coli and the associated antibiotic resistance gene in the anaerobic sludge. However, horizontal transfer of the plasmid encoding the antibiotic resistance gene was detected in the aerobic sludge by a cultivation method. A subpopulation of persister E. coli cells was also detected in the aerobic sludge. The findings of this study suggest potential areas of concern arising from pathogenic and antibiotic-resistant E. coli during both anaerobic and aerobic sludge treatment processes. PMID:28411227
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Mantilla-Calderon, David; Hong, Pei-Ying
2017-07-01
The presence of emerging biological pollutants in treated wastewater effluents has gained attention due to increased interest in water reuse. To evaluate the effectiveness of the removal of such contaminants by the conventional wastewater treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were assessed in microcosms of anaerobic and aerobic sludge. Results showed that E. coli PI7 decayed at a significantly lower rate under anaerobic conditions. Approximate half-lives were 32.4 ± 1.4 h and 5.9 ± 0.9 h in the anaerobic and aerobic microcosms, respectively. In the aerobic microcosms, after 72 h of operation, E. coli PI7 remained detectable, but no further decay was observed. Instead, 1 in every 10,000 E. coli cells was identified to be recalcitrant to decay and persist indefinitely in the sludge. ARGs associated with the E. coli PI7 strain were detected to have transferred to other native microorganisms in the sludge or were released to the liquid fraction upon host decay. Extracellular DNA quickly degraded in the liquid fraction of the aerobic sludge. In contrast, no DNA decay was detected in the anaerobic sludge water matrix throughout the 24-h sampling period. This study suggests an increased likelihood of environmental dispersion of ARGs associated with anaerobically treated wastewater effluents and highlights the potential importance of persister cells in the dissemination of E. coli in the environment during reuse events of treated wastewater. IMPORTANCE This study examines the decay kinetics of a pathogenic and antibiotic resistant strain of Escherichia coli in microcosms simulating biological treatment units of aerobic and anaerobic sludge. The results of this study point at a significantly prolonged persistence of the E. coli and the associated antibiotic resistance gene in the anaerobic sludge. However, horizontal transfer of the plasmid encoding the antibiotic resistance gene was detected in the aerobic sludge by a cultivation method. A subpopulation of persister E. coli cells was also detected in the aerobic sludge. The findings of this study suggest potential areas of concern arising from pathogenic and antibiotic-resistant E. coli during both anaerobic and aerobic sludge treatment processes. Copyright © 2017 Mantilla-Calderon and Hong.
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In vivo mapping of tumor oxygen consumption using (19)F MRI relaxometry.
Diepart, Caroline; Magat, Julie; Jordan, Bénédicte F; Gallez, Bernard
2011-06-01
Recently, we have developed a new electron paramagnetic resonance (EPR) protocol in order to estimate tissue oxygen consumption in vivo. Because it is crucial to probe the heterogeneity of response in tumors, the aim of this study was to apply our protocol, together with (19)F MRI relaxometry, to the mapping of the oxygen consumption in tumors. The protocol includes the continuous measurement of tumor po(2) during the following respiratory challenge: (i) basal values during air breathing; (ii) increasing po(2) values during carbogen breathing until saturation of tissue with oxygen; (iii) switching back to air breathing. We have demonstrated previously using EPR oximetry that the kinetics of return to the basal value after oxygen saturation are mainly governed by tissue oxygen consumption. This challenge was applied in hyperthyroid mice (generated by chronic treatment with L-thyroxine) and control mice, as hyperthyroidism is known to dramatically affect the oxygen consumption rate of tumor cells. Our recently developed snapshot inversion recovery MRI fluorocarbon oximetry technique allowed the po(2) return kinetics to be measured with a high temporal resolution. The kinetic constants (i.e. oxygen consumption rates) were higher for tumors from hyperthyroid mice than from control mice, data that are consistent with our previous EPR study. The corresponding histograms of the (19)F MRI data showed that the kinetic constants displayed a shift to the right for the hyperthyroid group, indicating a higher oxygen consumption in these tumors. The color maps showed a large heterogeneity in terms of oxygen consumption rate within a tumor. In conclusion, (19)F MRI relaxometry allows the noninvasive mapping of the oxygen consumption in tumors. The ability to assess the heterogeneity of tumor response is critical in order to identify potential tumor regions that might be resistant to treatment and therefore produce a poor response to therapy. Copyright © 2010 John Wiley & Sons, Ltd.
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Parathion causes secondary poisoning in a laughing gull breeding colony
White, D.H.; King, K.A.; Mitchell, C.A.; Hill, E.F.; Lamont, T.G.
1979-01-01
Use of organophosphate insecticides as replacements for the more persistent organochlorine compounds has increased dramatically in recent years. Organophosphates are desirable for field application because they break down rapidly in the environment and do not persist in animal tissues (Stickel 1974). Nevertheless, certain organophosphates are extremely toxic to wildlife for short periods after application and have caused widespread mortality among exposed animals (Mills 1973, Stickel 1974, 1975, Mendelssohn 1977, and Zinkl et al. 1978).
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Walmsley, Heather L
2011-07-01
'Deliberative democracy' is increasingly popular globally, as a means of securing public engagement with emerging health technologies and democratizing their governance. Architects of deliberative 'mini-publics' have tended, however, to privilege consensus within deliberation and the generation of 'action commitments' within a 'decisional context', despite widespread critique. Less attention has been paid to the phenomenon of persistent disagreement within constructed deliberative fora. This paper addresses this lacuna, performing a narrative analysis of four days of deliberation within one small group of demographically diverse public participants at the BC Biobank Deliberation (Vancouver, Canada, 2007). It reveals the value of listening to persistent deliberative disagreements. First, this paper argues that disagreements enable identification of deliberation and evaluation of its quality. Second, they generate insight into the deliberative process and the discursive means through which consensus can be achieved. Third, persistent deliberative disagreements can be creative of innovative governance solutions. In the case of the BC Biobank Deliberation, disagreements about compensation for biobank donors generated a range of suggestions for mediating between donor rights, corporate interests and societal needs--from tissue sample rentals to donor tax credits--suggestions that are unique to the existing academic and policy literature. Finally, this paper argues that practitioners should present persistent disagreements to public and policy audiences as an 'output' of deliberative democracy events. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Gemensky-Metzler, Anne J; Wilkie, David A
2004-01-01
The objective of this study was to describe the clinical, histologic and immunohistochemical features, the surgical treatment, and outcome of a cataract secondary to persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in a dog. A 4-month-old male Bloodhound dog presented for evaluation of a cataract. A complete ophthalmic examination and ocular ultrasonography were performed. A resorbing cataract with intralenticular hemorrhage, lens induced uveitis, and PHTVL/PHPV were diagnosed. Extracapsular cataract extraction using phacoemulsification was performed. A primary posterior capsulectomy was performed to remove a retrolental plaque with the posterior capsule; the excised plaque was submitted for histopathology and immunohistochemical staining. A 41-Diopter intraocular lens (IOL) was implanted. Functional vision was maintained postoperatively during the 21-month follow-up period. Histologically, the posterior capsule was coiled and exhibited duplication. The retrolental plaque was comprised of dense fibrous connective tissue, blood vessels, free red blood cells, hemosiderin-laden macrophages, a pocket of neural tissue and numerous perivascular mast cells. With immunohistochemical staining, the neural elements were determined to be glial cells compatible with astrocytes. Cataract secondary to PHTVL/PHPV can be successfully treated using phacoemulsification and planned posterior capsulectomy. Posterior lens capsule duplication, mast cells and astrocytic glial cells may be normal components of the fibrovascular retrolental plaque associated with PHTVL/PHPV.
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NASA Astrophysics Data System (ADS)
Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.
2013-06-01
Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.
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Fernández-Ruiz, Ramón; Redrejo, María Jesús; Friedrich, Eberhardt Josué; Ramos, Milagros; Fernández, Tamara
2014-08-05
This work presents the first application of total-reflection X-ray fluorescence (TXRF) spectrometry, a new and powerful alternative analytical method, to evaluation of the bioaccumulation kinetics of gold nanorods (GNRs) in various tissues upon intravenous administration in mice. The analytical parameters for developed methodology by TXRF were evaluated by means of the parallel analysis of bovine liver certified reference material samples (BCR-185R) doped with 10 μg/g gold. The average values (n = 5) achieved for gold measurements in lyophilized tissue weight were as follows: recovery 99.7%, expanded uncertainty (k = 2) 7%, repeatability 1.7%, detection limit 112 ng/g, and quantification limit 370 ng/g. The GNR bioaccumulation kinetics was analyzed in several vital mammalian organs such as liver, spleen, brain, and lung at different times. Additionally, urine samples were analyzed to study the kinetics of elimination of the GNRs by this excretion route. The main achievement was clearly differentiating two kinds of behaviors. GNRs were quickly bioaccumulated by highly vascular filtration organs such as liver and spleen, while GNRs do not show a bioaccumulation rates in brain and lung for the period of time investigated. In parallel, urine also shows a lack of GNR accumulation. TXRF has proven to be a powerful, versatile, and precise analytical technique for the evaluation of GNRs content in biological systems and, in a more general way, for any kind of metallic nanoparticles.
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Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto
2016-02-29
Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. Copyright © 2016 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin
2011-10-01
We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.
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The sequential tissue distribution of duck Tembusu virus in adult ducks.
Wu, Li; Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Ding, Leilei; Lin, Yuan; Li, Qimeng; He, Xijun; Chen, Qiusheng; Chen, Hualan
2014-01-01
In 2010, a novel Tembusu virus (TMUV) that caused a severe decrease in the egg production of ducks was isolated in southeast China. Given the novelty of this duck pathogen, little information is available regarding its pathogenesis. Here, we systematically investigated the replication kinetics of TMUV PTD2010 in adult male and female ducks. We found that PTD2010 was detectable in most of the parenchymatous organs as well as the oviduct and intestinal tract from days 1 to 7 after inoculation. Viral titers were maintained at high levels for at least 9 days in the spleen, kidney, bursa of Fabricius, brain, and ovary. No virus was detected in any of these organs or tissues at 18 days after inoculation. PTD2010, thus, causes systemic infections in male and female ducks; its replication kinetics show similar patterns in most organs, with the exception of the ovaries and testes.
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Mycobacterium tuberculosis infection modulates adipose tissue biology
Kühl, Anja A.; Kupz, Andreas; Vogelzang, Alexis; Mollenkopf, Hans-Joachim; Löwe, Delia; Bandermann, Silke; Dorhoi, Anca; Brinkmann, Volker
2017-01-01
Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection. Mice infected via aerosol showed infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)-negative F4/80+ cells, despite recruitment of CD3+, CD4+ and CD8+ T cells. Gene expression analysis of adipose tissue of aerosol Mtb-infected mice provided evidence for upregulated expression of genes associated with T cells and NK cells at 28 days post-infection. Strikingly, IFN-γ-producing NK cells and Mtb-specific CD8+ T cells were identified in perigonadal fat, specifically CD8+CD44-CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of these cells revealed that they expressed IFN-γ and the lectin-like receptor Klrg1 and down-regulated CD27 and CD62L, consistent with an effector phenotype of Mtb-specific CD8+ T cells. Sorted NK cells expressed higher abundance of Klrg1 upon infection, as well. Our results reveal the ability of Mtb to persist in adipose tissue in a stressed state, and that NK cells and Mtb-specific CD8+ T cells infiltrate infected adipose tissue where they produce IFN-γ and assume an effector phenotype. We conclude that adipose tissue is a potential niche for Mtb and that due to infection CD8+ T cells and NK cells are attracted to this tissue. PMID:29040326
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Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells
Takamura, Shiki
2018-01-01
Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that maintain TRM cells in different tissues. PMID:29904388
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It takes a tissue to make a tumor: epigenetics, cancer and the microenvironment
NASA Technical Reports Server (NTRS)
Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)
2001-01-01
How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.
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Tichauer, K M; Samkoe, K S; Klubben, W S; Hasan, T; Pogue, B W
2012-01-01
The quantification of tumor molecular expression in vivo could have a significant impact for informing and monitoring immerging targeted therapies in oncology. Molecular imaging of targeted tracers can be used to quantify receptor expression in the form of a binding potential (BP) if the arterial input curve or a surrogate of it is also measured. However, the assumptions of the most common approaches (reference tissue models) may not be valid for use in tumors. In this study, the validity of reference tissue models is investigated for use in tumors experimentally and in simulations. Three different tumor lines were grown subcutaneously in athymic mice and the mice were injected with a mixture of an epidermal growth factor receptor- (EGFR-) targeted fluorescent tracer and an untargeted fluorescent tracer. A one-compartment plasma input model demonstrated that the transport kinetics of both tracers were significantly different between tumors and all potential reference tissues, and using the reference tissue model resulted in a theoretical underestimation in BP of 50 ± 37%. On the other hand, the targeted and untargeted tracers demonstrated similar transport kinetics, allowing a dual-tracer approach to be employed to accurately estimate binding potential (with a theoretical error of 0.23 ± 9.07%). These findings highlight the potential for using a dual-tracer approach to quantify receptor expression in tumors with abnormal hemodynamics, possibly to inform the choice or progress of molecular cancer therapies. PMID:23022732
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Lüttge, U
1966-03-01
The transport of chloride in isolated tissue from Nepenthes pitchers was investigated using (36)Cl(-), an Aminco-Cotlove chloride-titrator for the determinations of Cl(-) concentrations, and KCN and AsO 4 (-) -as metabolic inhibitors.The tissue was brought in contact with different experimental solutions (=medium). The surface corresponding to the outside of the pitchers was cut with a razor blade to remove the cutinized epidermal layer. At this surface the Cl(-) uptake from the medium is a metabolic process which depends on the Cl(-)-concentration of the medium in a manner that corresponds to the MICHAELIS-MENTEN kinetics. The Michaelis-constant of this transport step was 3×10(-2)M. The Cl(-)-efflux into the medium, however, is a passive process.The opposite surface of the tissue slices (corresponding to the inside of the pitchers) carries the glands. The chloride secretion taking place here is also dependent on metabolism. In vitro it occurs even when a high gradient of chloride concentration has been set up between the medium and the solution which is in contact with the glands. In vivo the Cl(-)-concentration of the pitcher fluid and the amount of Cl(-) per gram of tissue water are almost equal.The rôle of chloride in the physiology of Nepenthes is still under investigation, A correlation between the chloride content of the pitcher fluid and its enzymatic activity (Casein-test), however, could already be demonstrated.
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San Juan Serrano, F; Fernández González, M; Sánchez López, J L; García Martín, L O
1995-09-01
Initial rate and affinity studies on mantle Mytilus phosphorylase a were carried out in order to find possible differences in its kinetic properties with respect to phosphorylase b. Phosphorylase a was not stimulated for any AMP concentrations. Michaelis constants (Km) are 0.05 mg/ml glycogen, 1.15 mM inorganic phosphate and 1.50 mM glucose-1-phosphate. The Kms for the substrates, in the direction of glycogen breakdown, are enhanced by non-saturating concentrations of cosubstrate, without reducing the apparent maximum velocity. First order and hyperbolic kinetics and values of the allosteric constant smaller than 2 were observed. These results suggest a catalytic mechanism different to that shown for mantle Mytilus phosphorylase b.
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Biological effects of radiation, metabolic and replication kinetics alterations
NASA Technical Reports Server (NTRS)
Post, J.
1972-01-01
The biological effects of radiation upon normal and cancerous tissues were studied. A macromolecular precursor of DNA, 3ETdR, was incorporated into the cell nucleus during synthesis and provided intranuclear beta radiation. Tritium labeled cells were studied with autoradiographic methods; cell cycle kinetics were determined and cell functions modified by radiation dosage or by drugs were also evaluated. The long term program has included; (1) effects of radiation on cell replication and the correlation with incorporated dose levels, (2) radiation induced changes in cell function, viz., the response of beta irradiated spleen lymphocytes to antigenic stimulation by sheep red blood cells (SRBC), (3) kinetics of tumor and normal cell replication; and (4) megakaryocyte formation and modification by radiomimetic drugs.
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McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.
2011-01-01
Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847
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Migration of lymphocytes on fibronectin-coated surfaces: temporal evolution of migratory parameters
NASA Technical Reports Server (NTRS)
Bergman, A. J.; Zygourakis, K.; McIntire, L. V. (Principal Investigator)
1999-01-01
Lymphocytes typically interact with implanted biomaterials through adsorbed exogenous proteins. To provide a more complete characterization of these interactions, analysis of lymphocyte migration on adsorbed extracellular matrix proteins must accompany the commonly performed adhesion studies. We report here a comparison of the migratory and adhesion behavior of Jurkat cells (a T lymphoblastoid cell line) on tissue culture treated and untreated polystyrene surfaces coated with various concentrations of fibronectin. The average speed of cell locomotion showed a biphasic response to substrate adhesiveness for cells migrating on untreated polystyrene and a monotonic decrease for cells migrating on tissue culture-treated polystyrene. A modified approach to the persistent random walk model was implemented to determine the time dependence of cell migration parameters. The random motility coefficient showed significant increases with time when cells migrated on tissue culture-treated polystyrene surfaces, while it remained relatively constant for experiments with untreated polystyrene plates. Finally, a cell migration computer model was developed to verify our modified persistent random walk analysis. Simulation results suggest that our experimental data were consistent with temporally increasing random motility coefficients.
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Stem Cells in Skeletal Tissue Engineering: Technologies and Models
Langhans, Mark T.; Yu, Shuting; Tuan, Rocky S.
2017-01-01
This review surveys the use of pluripotent and multipotent stem cells in skeletal tissue engineering. Specific emphasis is focused on evaluating the function and activities of these cells in the context of development in vivo, and how technologies and methods of stem cell-based tissue engineering for stem cells must draw inspiration from developmental biology. Information on the embryonic origin and in vivo differentiation of skeletal tissues is first reviewed, to shed light on the persistence and activities of adult stem cells that remain in skeletal tissues after embryogenesis. Next, the development and differentiation of pluripotent stem cells is discussed, and some of their advantages and disadvantages in the context of tissue engineering is presented. The final section highlights current use of multipotent adult mesenchymal stem cells, reviewing their origin, differentiation capacity, and potential applications to tissue engineering. PMID:26423296
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Aging of microstructural compartments in human compact bone
NASA Technical Reports Server (NTRS)
Akkus, Ozan; Polyakova-Akkus, Anna; Adar, Fran; Schaffler, Mitchell B.
2003-01-01
Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the osteons and similar to the "fully mineralized" stage of primary bone. The results of this study demonstrated that unremodeled compartments of bone grow older through maturation and growth of mineral crystals in a protracted fashion. However, the secondary osteonal remodeling impedes this aging process and maintains the mean tissue age fairly constant over decades. Therefore, slowing of remodeling may lead to brittle bone tissue through accumulation of fully mineralized tissue fragments.
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CO activation pathways and the mechanism of Fischer–Tropsch synthesis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ojeda, Manuel; Nabar, Rahul P.; Nilekar, Anand U.
2010-06-15
Unresolved mechanistic details of monomer formation in Fischer–Tropsch synthesis (FTS) and of its oxygen rejection routes are addressed here by combining kinetic and theoretical analyses of elementary steps on representative Fe and Co surfaces saturated with chemisorbed CO. These studies provide experimental and theoretical evidence for hydrogen-assisted CO activation as the predominant kinetically-relevant step on Fe and Co catalysts at conditions typical of FTS practice. H2 and CO kinetic effects on FTS rates and oxygen rejection selectivity (as H2O or CO2) and density functional theory estimates of activation barriers and binding energies are consistent with H-assisted CO dissociation, but notmore » with the previously accepted kinetic relevance of direct CO dissociation and chemisorbed carbon hydrogenation elementary steps. H-assisted CO dissociation removes O-atoms as H2O, while direct dissociation forms chemisorbed oxygen atoms that desorb as CO2. Direct CO dissociation routes are minor contributors to monomer formation on Fe and may become favored at high temperatures on alkali-promoted catalysts, but not on Co catalysts, which remove oxygen predominantly as H2O because of the preponderance of Hassisted CO dissociation routes. The merging of experiment and theory led to the clarification of persistent mechanistic issues previously unresolved by separate experimental and theoretical inquiries.« less
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Olsen, Ansgar S.; Sarras, Michael P.; Leontovich, Alexey; Intine, Robert V.
2012-01-01
Metabolic memory (MM) is the phenomenon whereby diabetes complications persist and progress after glycemic recovery is achieved. Here, we present data showing that MM is heritable and that the transmission correlates with hyperglycemia-induced DNA hypomethylation and aberrant gene expression. Streptozocin was used to induce hyperglycemia in adult zebrafish, and then, following streptozocin withdrawal, a recovery phase was allowed to reestablish a euglycemic state. Blood glucose and serum insulin returned to physiological levels during the first 2 weeks of the recovery phase as a result of pancreatic β-cell regeneration. In contrast, caudal fin regeneration and skin wound healing remained impaired to the same extent as in diabetic fish, and this impairment was transmissible to daughter cell tissue. Daughter tissue that was never exposed to hyperglycemia, but was derived from tissue that was, did not accumulate AGEs or exhibit increased levels of oxidative stress. However, CpG island methylation and genome-wide microarray expression analyses revealed the persistence of hyperglycemia-induced global DNA hypomethylation that correlated with aberrant gene expression for a subset of loci in this daughter tissue. Collectively, the data presented here implicate the epigenetic mechanism of DNA methylation as a potential contributor to the MM phenomenon. PMID:22228713
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Vance, Richard R; Nevai, Andrew L
2007-03-21
Can a difference in the heights at which plants place their leaves, a pattern we call canopy partitioning, make it possible for two competing plant species to coexist? To find out, we examine a model of clonal plants living in a nonseasonal environment that relates the dynamical behavior and competitive abilities of plant populations to the structural and functional features of the plants that form them. This examination emphasizes whole plant performance in the vertical light gradient caused by self-shading. This first of three related papers formulates a prototype single species Canopy Structure Model from biological first principles and shows how all plant properties work together to determine population persistence and equilibrium abundance. Population persistence is favored, and equilibrium abundance is increased, by high irradiance, high maximum photosynthesis rate, rapid saturation of the photosynthetic response to increased irradiance, low tissue respiration rate, small amounts of stem and root tissue necessary to support the needs of leaves, and low density of leaf, stem, and root tissues. In particular, equilibrium abundance decreases as mean leaf height increases because of the increased cost of manufacturing and maintaining stem tissue. All conclusions arise from this formulation by straightforward analysis. The argument concludes by stating this formulation's straightforward extension, called a Canopy Partitioning Model, to two competing species.
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Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M
2015-12-01
Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.
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Imaging Mass Spectrometry for Characterization of Atrial Fibrillation Subtypes.
Klein, Oliver; Hanke, Thorsten; Nerbrich, Grit; Yan, Junfeng; Schubert, Benedikt; Giavalisco, Patrick; Noack, Frank; Thiele, Herbert; Mohamed, Salah A
2018-05-13
Atrial fibrillation (AF) is a cardiac arrhythmia characterized by a rapid and irregular heart rhythm. AF types, paroxysmal (PX), persistent (PE) and long-lasting persistent (LSP), requires differences in clinical management. Unfortunately, a significant proportion of AF patients are clinical misclassified. Therefore, our study aim that MALDI-Imaging (IMS) is valuable as a diagnostic aid in AF subtypes assessment. Patients were clinically classified according guidelines of the European Society of Cardiology. FFPE tissue specimens from PE, PX and LSP subtype were analysed by MALDI-IMS and evaluated by multi-statistical testing. Proteins were subsequent identified using LC-MS/MS and findings were confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology RESULT: : Determined characteristic peptide signatures and peptide values facilitate to distinguish between PE, PE and LSP arterial fibrillation subtypes. In particular, peptide values from alpha 1 type I collagen were identified that were significantly higher in LSP and PE tissue but not in PX myocardial AF tissue. These findings were confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology. Our results represent an improvement in AF risk stratification by using MALDI-IMS as a promising approach for AF tissue assessment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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McGonigle, John E; Purves, Joanne; Rolff, Jens
2016-06-01
Survival of bacteria within host cells and tissues presents a challenge to the immune systems of higher organisms. Escape from phagocytic immune cells compounds this issue, as immune cells become potential vehicles for pathogen dissemination. However, the duration of persistence within phagocytes and its contribution to pathogen load has yet to be determined. We investigate the immunological significance of intracellular persistence within the insect model Tenebrio molitor, assessing the extent, duration and location of bacterial recovery during a persistent infection. Relative abundance of Staphylococcus aureus in both intracellular and extracellular fractions was determined over 21 days, and live S. aureus were successfully recovered from both the hemolymph and within phagocytic immune cells across the entire time course. The proportion of bacteria recovered from within phagocytes also increased over time. Our results show that to accurately estimate pathogen load it is vital to account for bacteria persisting within immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics.
Pascal, Robert; Pross, Addy; Sutherland, John D
2013-11-06
A sudden transition in a system from an inanimate state to the living state-defined on the basis of present day living organisms-would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages-dynamic kinetic stability (DKS)-which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred.
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NASA Technical Reports Server (NTRS)
Parks, B. M.; Spalding, E. P.; Evans, M. L. (Principal Investigator)
1999-01-01
Photoreceptor proteins of the phytochrome family mediate light-induced inhibition of stem (hypocotyl) elongation during the development of photoautotrophy in seedlings. Analyses of overt mutant phenotypes have established the importance of phytochromes A and B (phyA and phyB) in this developmental process, but kinetic information that would augment emerging molecular models of phytochrome signal transduction is absent. We have addressed this deficiency by genetically dissecting phytochrome-response kinetics, after having solved the technical issues that previously limited growth studies of small Arabidopsis seedlings. We show here, with resolution on the order of minutes, that phyA initiated hypocotyl growth inhibition upon the onset of continuous red light. This primary contribution of phyA began to decrease after 3 hr of irradiation, the same time at which immunochemically detectable phyA disappeared and an exclusively phyB-dependent phase of inhibition began. The sequential and coordinated actions of phyA and phyB in red light were not observed in far-red light, which inhibited growth persistently through an exclusively phyA-mediated pathway.
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Biomaterials in the repair of sports injuries
NASA Astrophysics Data System (ADS)
Ducheyne, Paul; Mauck, Robert L.; Smith, Douglas H.
2012-08-01
The optimal stimulation of tissue regeneration in bone, cartilage and spinal cord injuries involves a judicious selection of biomaterials with tailored chemical compositions, micro- and nanostructures, porosities and kinetic release properties for the delivery of relevant biologically active molecules.
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Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong
2014-01-01
The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed 11C-labeled PET probes 11C-ITMM and 11C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared 11C-ITMM and 11C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with 11C-ITDM than with 11C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm-3 for 11C-ITMM and 3.6 mL∙cm-3 for 11C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of 11C-ITMM and 11C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that 11C-ITDM may be superior to 11C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with 11C-ITDM were higher than those of 11C-ITMM. Clinical studies of 11C-ITDM in humans will be necessary in the future. PMID:24795840
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Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong
2014-01-01
The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.
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NASA Astrophysics Data System (ADS)
Bisdas, Sotirios; Konstantinou, George N.; Sherng Lee, Puor; Thng, Choon Hua; Wagenblast, Jens; Baghi, Mehran; San Koh, Tong
2007-10-01
The objective of this work was to evaluate the feasibility of a two-compartment distributed-parameter (DP) tracer kinetic model to generate functional images of several physiologic parameters from dynamic contrast-enhanced CT data obtained of patients with extracranial head and neck tumors and to compare the DP functional images to those obtained by deconvolution-based DCE-CT data analysis. We performed post-processing of DCE-CT studies, obtained from 15 patients with benign and malignant head and neck cancer. We introduced a DP model of the impulse residue function for a capillary-tissue exchange unit, which accounts for the processes of convective transport and capillary-tissue exchange. The calculated parametric maps represented blood flow (F), intravascular blood volume (v1), extravascular extracellular blood volume (v2), vascular transit time (t1), permeability-surface area product (PS), transfer ratios k12 and k21, and the fraction of extracted tracer (E). Based on the same regions of interest (ROI) analysis, we calculated the tumor blood flow (BF), blood volume (BV) and mean transit time (MTT) by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for PS imaging. We compared the corresponding values by using Bland-Altman plot analysis. We outlined 73 ROIs including tumor sites, lymph nodes and normal tissue. The Bland-Altman plot analysis revealed that the two methods showed an accepted degree of agreement for blood flow, and, thus, can be used interchangeably for measuring this parameter. Slightly worse agreement was observed between v1 in the DP model and BV but even here the two tracer kinetic analyses can be used interchangeably. Under consideration of whether both techniques may be used interchangeably was the case of t1 and MTT, as well as for measurements of the PS values. The application of the proposed DP model is feasible in the clinical routine and it can be used interchangeably for measuring blood flow and vascular volume with the commercially available reference standard of the deconvolution-based approach. The lack of substantial agreement between the measurements of vascular transit time and permeability-surface area product may be attributed to the different tracer kinetic principles employed by both models and the detailed capillary tissue exchange physiological modeling of the DP technique.
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Roberts, Jack C; Ward, Emily E; Merkle, Andrew C; O'Connor, James V
2007-05-01
To assess the possibility of injury as a result of behind armor blunt trauma (BABT), a study was undertaken to determine the conditions necessary to produce the 44-mm clay deformation as set forth in the National Institute of Justice (NIJ) Standard 0101.04. These energy levels were then applied to a three-dimensional Human Torso Finite Element Model (HTFEM) with soft armor vest. An examination will be made of tissue stresses to determine the effects of the increased kinetic energy levels on the probability of injury. A clay finite element model (CFEM) was created with a material model that required nonlinear properties for clay. To determine these properties empirically, the results from the CFEM were matched with experimental drop tests. A soft armor vest was modeled over the clay to create a vest over clay block finite element model (VCFEM) and empirical methods were again used to obtain material properties for the vest from experimental ballistic testing. Once the properties for the vest and clay had been obtained, the kinetic energy required to produce a 44-mm deformation in the VCFEM was determined through ballistic testing. The resulting kinetic energy was then used in the HTFEM to evaluate the probability of BABT. The VCFEM, with determined clay and vest material properties, was exercised with the equivalent of a 9-mm (8-gm) projectile at various impact velocities. The 44-mm clay deformation was produced with a velocity of 785 m/s. This impact condition (9-mm projectile at 785 m/s) was used in ballistic exercises of the HTFEM, which was modeled with high-strain rate human tissue properties for the organs. The impact zones were over the sternum anterior to T6 and over the liver. The principal stresses in both soft and hard tissue at both locations exceeded the tissue tensile strength. This study indicates that although NIJ standard 0101.04 may be a good guide to soft armor failure, it may not be as good a guide in BABT, especially at large projectile kinetic energies. Further studies, both numerical and experimental, are needed to assist in predicting injury using the NIJ standard.
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Bullich, Santiago; Barthel, Henryk; Koglin, Norman; Becker, Georg A; De Santi, Susan; Jovalekic, Aleksandar; Stephens, Andrew W; Sabri, Osama
2017-11-24
Accurate amyloid PET quantification is necessary for monitoring amyloid-beta accumulation and response to therapy. Currently, most of the studies are analyzed using the static standardized uptake value ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were: (1) to validate a non-invasive kinetic modeling approach for 18 F-florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and (2) to assess the impact of CBF changes and radiotracer clearance on SUVRs and non-invasive kinetic modeling data in 18 F-florbetaben PET. Methods: Data from twenty subjects (10 patients with probable Alzheimer's dementia/ 10 healthy volunteers) were used to compare the binding potential (BP ND ) obtained from the full kinetic analysis to the SUVR and to non-invasive tracer kinetic methods (simplified reference tissue model (SRTM), and multilinear reference tissue model 2 (MRTM2)). Different approaches using shortened or interrupted acquisitions were compared to the results of the full acquisition (0-140 min). Simulations were carried out to assess the effect of CBF and radiotracer clearance changes on SUVRs and non-invasive kinetic modeling outputs. Results: A 0-30 and 120-140 min dual time-window acquisition protocol using appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BP ND obtained using full and dual time-window (2TW) acquisition protocols (BP ND,2TW =0.01+ 1.00 BP ND,FULL , R2=0.97 (MRTM2); BP ND,2TW = 0.05+ 0.92·BP ND,FULL , R2=0.93 (SRTM)). Simulations showed a limited impact of CBF and radiotracer clearance changes on MRTM parameters and SUVRs. Conclusion: This study demonstrates accurate non-invasive kinetic modeling of 18 F-florbetaben PET data using a dual time-window acquisition protocol, thus providing a good compromise between quantification accuracy, scan duration and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-beta load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which a maximum quantification accuracy is desired, this non-invasive dual time-window acquisition protocol and kinetic analysis is recommended. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Kimura, Yasuyuki; Siméon, Fabrice G; Zoghbi, Sami S; Zhang, Yi; Hatazawa, Jun; Pike, Victor W; Innis, Robert B; Fujita, Masahiro
2012-02-01
A new PET ligand, 3-fluoro-5-(2-(2-(18)F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (18F-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring 18F-SP203 binding in the brain. Nine healthy subjects were injected with 18F-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. As a measure of ligand binding, we compared total distribution volume (VT) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated VT by the ratio of radioactivity in the brain to the concentration of 18F-SP203 in arterial plasma at 120 min, and the kinetic method calculated VT by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. VT obtained via the equilibrium method was highly correlated with VT obtained via kinetic modeling. Inter-subject variability of VT obtained via the equilibrium method was slightly smaller than VT obtained via the kinetic method. VT obtained via the equilibrium method was ~10% higher than VT obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18F-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated VT values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using 18F-SP203, the equilibrium method is more efficient because it requires much less data. Copyright © 2011. Published by Elsevier Inc.
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The Foot-and-Mouth Disease Carrier State Divergence in Cattle
Eschbaumer, Michael; Rekant, Steven I.; Pacheco, Juan M.; Smoliga, George R.; Hartwig, Ethan J.; Rodriguez, Luis L.
2016-01-01
ABSTRACT The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis. IMPORTANCE The existence of a prolonged, asymptomatic carrier state is a political impediment for control and potential eradication of foot-and-mouth disease (FMD). When FMD outbreaks occur, they are often extinguished by massive depopulation of livestock due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty over the biological relevance of FMD virus (FMDV) persistence. The work described here elucidates aspects of the FMDV carrier state in cattle which may facilitate identification and/or abrogation of asymptomatic FMDV infection. The divergence between animals that clear infection and those that develop persistent infection was demonstrated to occur earlier than previously established. The host antiviral response in tissues maintaining persistent FMDV was downregulated, whereas upregulation of IFN-λ mRNA was found in the epithelium of cattle that had recently cleared the infection. This suggests that the clearing of FMDV infection is associated with an enhanced mucosal antiviral response, whereas FMDV persistence is associated with suppression of the host antiviral response. PMID:27147736
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Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.
Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail
2016-11-01
Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Occurrence of human bocaviruses and parvovirus 4 in solid tissues.
Norja, Päivi; Hedman, Lea; Kantola, Kalle; Kemppainen, Kaisa; Suvilehto, Jari; Pitkäranta, Anne; Aaltonen, Leena-Maija; Seppänen, Mikko; Hedman, Klaus; Söderlund-Venermo, Maria
2012-08-01
Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. Copyright © 2012 Wiley Periodicals, Inc.
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Van Iterson, E H; Smith, J R; Olson, T P
2018-03-25
In contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on-transition is unclear. This study tested whether exercise on-transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O 2 pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O 2store ) contributions to V˙O 2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF. Beat-to-beat HR and breath-to-breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square-wave ergometry at 60% V˙O 2peak (46 ± 14 vs 125 ± 54-W, P < .001). Temporal responses across V˙ E , V˙O 2 and O 2 pulse were assessed for the exercise on-transition using single exponential model Phase II on-kinetic time constants (τ = time to reach 63% steady-state rise). Breath-to-breath gas fractions and respiratory flows were used to determine O 2stores . HF vs controls: τ for V˙ E (137 ± 93 vs 74 ± 40-seconds, P = .03), V˙O 2 (60 ± 40 vs 23 ± 5-seconds, P = .03) and O 2 pulse (28 ± 18 vs 23 ± 15-seconds, P = .59). Within HF, τ for V˙ E differed from O 2 pulse (P < .02), but not V˙O 2 . Exercise V˙ E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88-mL min -1 W -1 , P < .001). Exercise on-transition O 2store depletion in HF exceeded controls, generally persisting to end-exercise. These data suggest HF demonstrated exercise on-transition O 2store depletion (high O 2store contribution to V˙O 2 ) coupled with dyssynchronous V˙ E , V˙O 2 and O 2 pulse kinetics-not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise on-transition. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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... can improve blood clotting. Supplements of calcium and vitamin D are often taken if the cholestasis persists, but they are not very effective in preventing loss of bone tissue. Resources In This Article Figure 1 View of the Liver and Gallbladder ...
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Tibboel, Jeroen; Keijzer, Richard; Reiss, Irwin; de Jongste, Johan C; Post, Martin
2014-06-01
The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters. Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema. MSCs were administered intratracheally or intravenously, before or after elastase injection. Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration. Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up. Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up. Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology. Intratracheal MSC treatment did not modify lung function or histology. In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema. Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function. Intratracheal MSC treatment had no effect on lung function or histology.
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Beels, Laurence; Werbrouck, Joke; Thierens, Hubert
2010-09-01
Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yu, P.; Block, H; Doiron, K
Conventional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capablemore » of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). These results suggest that SR-FTIRM plus the multivariate analyses can be used to identify spectral features associated with the molecular structure of endosperm from grains with different biodegradation kinetics, especially in relation to protein structure. The Novel synchrotron radiation-based bioanalytical technique provides a new approach for plant seed structural molecular studies at ultraspatial resolution and within intact tissue in relation to nutrient availability.« less
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Jensen-Kondering, Ulf; Williamson, David J.; Sitnikov, Sergey; Sawiak, Stephen J.; Aigbirhio, Franklin I.; Hong, Young T.
2017-01-01
Purpose Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity. Methods Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions. Results As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2. Conclusions Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging. PMID:29091934
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Fryer, Tim D; Ejaz, Sohail; Jensen-Kondering, Ulf; Williamson, David J; Sitnikov, Sergey; Sawiak, Stephen J; Aigbirhio, Franklin I; Hong, Young T; Baron, Jean-Claude
2017-01-01
Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity. Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions. As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2. Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, N.; Yu, P
2010-01-01
Barley varieties have similar chemical composition but exhibit different rumen degradation kinetics and nutrient availability. These biological differences may be related to molecular, structural, and chemical makeup among the seed endosperm tissue. No detailed study was carried out. The objectives of this study were: (1) to use a molecular spectroscopy technique, synchrotron-based Fourier transform infrared microspectroscopy (SFTIRM), to determine the microchemical-structural features in seed endosperm tissue of six developed barley varieties; (2) to study the relationship among molecular-structural characteristics, degradation kinetics, and nutrient availability in six genotypes of barley. The results showed that inherent microchemical-structural differences in the endosperm amongmore » the six barley varieties were detected by the synchrotron-based analytical technique, SFTIRM, with the univariate molecular spectral analysis. The SFTIRM spectral profiles differed (P < 0.05) among the barley samples in terms of the peak ratio and peak area and height intensities of amides I (ca. 1650 cm{sup -1}) and II (ca. 1550 cm{sup -1}), cellulosic compounds (ca. 1240 cm{sup -1}), CHO component peaks (the first peak at the region ca. 1184-1132 cm{sup -1}, the second peak at ca. 1132-1066 cm{sup -1}, and the third peak at ca. 1066-950 cm{sup -1}). With the SFTIRM technique, the structural characteristics of the cereal seeds were illuminated among different cultivars at an ultraspatial resolution. The structural differences of barley seeds may be one reason for the various digestive behaviors and nutritive values in ruminants. The results show weak correlations between the functional groups spectral data (peak area, height intensities, and ratios) and rumen biodegradation kinetics (rate and extent of nutrient degradation). Weak correlations may indicate that limited variations of these six barley varieties might not be sufficient to interpret the relationship between spectroscopic information and the nutrient value of barley grain, although significant differences in biodegradation kinetics were observed. In conclusion, the studies demonstrated the potential of ultraspatially resolved synchrotron based technology (SFTIRM) to reveal the structural and chemical makeup within cellular and subcellular dimensions without destruction of the inherent structure of cereal grain tissue.« less
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Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir
2014-08-15
The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractionsmore » from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.« less
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Experimental Infection of Pig-Tailed Macaques (Macaca nemestrina) with Mycoplasma genitalium.
Wood, Gwendolyn E; Patton, Dorothy L; Cummings, Peter K; Iverson-Cabral, Stefanie L; Totten, Patricia A
2017-02-01
Mycoplasma genitalium is an underappreciated cause of human reproductive tract disease, characterized by persistent, often asymptomatic, infection. Building on our previous experiments using a single female pig-tailed macaque as a model for M. genitalium infection (G. E. Wood, S. L. Iverson-Cabral, D. L. Patton, P. K. Cummings, Y. T. Cosgrove Sweeney, and P. A. Totten, Infect Immun 81:2938-2951, 2013, https://doi.org/10.1128/IAI.01322-12), we cervically inoculated eight additional animals, two of which were simultaneously inoculated in salpingeal tissue autotransplanted into abdominal pockets. Viable M. genitalium persisted in the lower genital tract for 8 weeks in three animals, 4 weeks in two, and 1 week in one; two primates resisted infection. In both animals inoculated in salpingeal pockets, viable M. genitalium was recovered for 2 weeks. Recovery of viable M. genitalium from lower genital tract specimens was improved by diluting the specimen in broth and by Vero cell coculture. Ascension to upper reproductive tract tissues was not detected, even among three persistently infected animals. M. genitalium-specific serum antibodies targeting the immunodominant MgpB and MgpC proteins appeared within 1 week in three animals inoculated both cervically and in salpingeal pockets and in one of three persistently infected animals inoculated only in the cervix. M. genitalium-specific IgG, but not IgA, was detected in cervical secretions of serum antibody-positive animals, predominantly against MgpB and MgpC, but was insufficient to clear M. genitalium lower tract infection. Our findings further support female pig-tailed macaques as a model of M. genitalium infection, persistence, and immune evasion. Copyright © 2017 American Society for Microbiology.
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Ghosh, Justin; Sepahpour, Ali; Chan, Kim H; Singarayar, Suresh; McGuire, Mark A
2013-05-01
Persistent phrenic nerve palsy is the most frequent complication of cryoballoon ablation for atrial fibrillation and can be disabling. To describe a technique-immediate balloon deflation (IBD)-for the prevention of persistent phrenic nerve palsy, provide data for its use, and describe in vitro simulations performed to investigate the effect of IBD on the atrium and pulmonary vein. Cryoballoon procedures for atrial fibrillation were analyzed retrospectively (n = 130). IBD was performed in patients developing phrenic nerve dysfunction (n = 22). In vitro simulations were performed by using phantoms. No adverse events occurred, and all patients recovered normal phrenic nerve function before leaving the procedure room. No patient developed persistent phrenic nerve palsy. The mean cryoablation time to onset of phrenic nerve dysfunction was 144 ± 64 seconds. Transient phrenic nerve dysfunction was seen more frequently with the 23-mm balloon than with the 28-mm balloon (11 of 39 cases vs 11 of 81 cases; P = .036). Balloon rewarming was faster following IBD. The time to return to 0 and 20° C was shorter in the IBD group (6.7 vs 8.9 seconds; P = .007 and 16.7 vs 37.6 seconds; P<.0001). In vitro simulations confirmed that IBD caused more rapid tissue warming (time to 0°C, 14.0 ± 3.4 seconds vs 46.0 ± 8.1; P = .0001) and is unlikely to damage the atrium or pulmonary vein. IBD results in more rapid tissue rewarming, causes no adverse events, and appears to prevent persistent phrenic nerve palsy. Simulations suggest that IBD is unlikely to damage the atrium or pulmonary vein. Copyright © 2013 Heart Rhythm Society. All rights reserved.
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Andermatt, Simon; Papadopoulou, Athina; Radue, Ernst-Wilhelm; Sprenger, Till; Cattin, Philippe
2017-09-01
Some gadolinium-enhancing multiple sclerosis (MS) lesions remain T1-hypointense over months ("persistent black holes, BHs") and represent areas of pronounced tissue loss. A reduced conversion of enhancing lesions to persistent BHs could suggest a favorable effect of a medication on tissue repair. However, the individual tracking of enhancing lesions can be very time-consuming in large clinical trials. We created a semiautomated workflow for tracking the evolution of individual MS lesions, to calculate the proportion of enhancing lesions becoming persistent BHs at follow-up. Our workflow automatically coregisters, compares, and detects overlaps between lesion masks at different time points. We tested the algorithm in a data set of Magnetic Resonance images (1.5 and 3T; spin-echo T1-sequences) from a phase 3 clinical trial (n = 1,272), in which all enhancing lesions and all BHs had been previously segmented at baseline and year 2. The algorithm analyzed the segmentation masks in a longitudinal fashion to determine which enhancing lesions at baseline turned into BHs at year 2. Images of 50 patients (192 enhancing lesions) were also reviewed by an experienced MRI rater, blinded to the algorithm results. In this MRI data set, there were no cases that could not be processed by the algorithm. At year 2, 417 lesions were classified as persistent BHs (417/1,613 = 25.9%). The agreement between the rater and the algorithm was > 98%. Due to the semiautomated procedure, this algorithm can be of great value in the analysis of large clinical trials, when a rater-based analysis would be time-consuming. Copyright © 2017 by the American Society of Neuroimaging.
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McIntosh, J. E. A.; Lutwak-Mann, C.
1972-01-01
1. To investigate the influence of hormonal conditions upon the kinetics of zinc transport, specific radioactivity of 65Zn was determined in certain tissues and fluids from unmated or pregnant rabbits during the first half of gestation. 2. Compartmental analysis was used to find the simplest mathematical model that simulated satisfactorily tracer behaviour. Models were fitted to experimental results by a numerical procedure using a computer. 3. The kinetics of zinc exchange in most tissues investigated could adequately be described by a three-compartment model, in which total tissue zinc content was divided into a rapidly exchanging pool, with a turnover time of about 1h, and a slowly exchanging pool, the turnover time of which was in liver 15h, in peak-stage corpus luteum 8h, and in the other tissues 30–70h. 4. In rabbit endometrium zinc transport varied with hormonal conditions, the turnover rate being higher in non-pregnant than pregnant endometrium. 5. Uptake of 65Zn by uterine fluid was slow, and in the free-lying embryos (blastocysts) slower still, in keeping with uterine fluid acting as carrier of zinc into the unimplanted embryos. 6. In placental tissue zinc transport varied with gestational stage. Foetal placenta exchanged zinc with blood plasma four times faster than maternal placenta. In foetuses zinc turnover time and flux equalled that of the slow zinc compartment in foetal placenta. 7. Corpus luteum on days 5–6 of gestation showed peak specific radioactivity and zinc flux values, which exceeded those of all other tissues. 8. In liver the slow zinc compartment had a higher rate of turnover than corresponding compartments in tissues other than peak-stage corpus luteum, but no hormone-dependent changes were observed. 9. Zinc uptake by erythrocytes was the slowest of all examined. PMID:5073239
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Matrix Metalloproteinase Responsive Delivery of Myostatin Inhibitors.
Braun, Alexandra C; Gutmann, Marcus; Ebert, Regina; Jakob, Franz; Gieseler, Henning; Lühmann, Tessa; Meinel, Lorenz
2017-01-01
The inhibition of myostatin - a member of the transforming growth factor (TGF-β) family - drives regeneration of functional skeletal muscle tissue. We developed a bioresponsive drug delivery system (DDS) linking release of a myostatin inhibitor (MI) to inflammatory flares of myositis to provide self-regulated MI concentration gradients within tissues of need. A protease cleavable linker (PCL) - responding to MMP upregulation - is attached to the MI and site-specifically immobilized on microparticle surfaces. The PCL disintegrated in a matrix metalloproteinase (MMP) 1, 8, and particularly MMP-9 concentration dependent manner, with MMP-9 being an effective surrogate biomarker correlating with the activity of myositis. The bioactivity of particle-surface bound as well as released MI was confirmed by luciferase suppression in stably transfected HEK293 cells responding to myostatin induced SMAD phosphorylation. We developed a MMP-responsive DDS for MI delivery responding to inflammatory flare of a diseased muscle matching the kinetics of MMP-9 upregulation, with MMP-9 kinetics matching (patho-) physiological myostatin levels. ᅟ: Graphical Abstract Schematic illustration of the matrix metalloproteinase responsive delivery system responding to inflammatory flares of muscle disease. The protease cleavable linker readily disintegrates upon entry into the diseased tissue, therby releasing the mystatin inhibitor.
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Ueberschär, Karl-Heinz; Dänicke, Sven; Matthes, Siegfried
2007-02-01
Technical short chain chlorinated paraffins (C10-C13 with 60% chlorine) were fed to 93 laying hens from 24 to 32 weeks of age in increasing concentrations of up to 100 mg/kg feed. No significant influence on health, relative organ weights or performance (laying intensity, egg weight, feed consumption) was noted. The chlorinated paraffin content of the tissues was linearly related to the concentration of short chain paraffins of the feed. The highest concentrations were found in abdominal fat, egg yolk and fatty tissues. Breast muscle, egg albumen and bile fluid contained minimal or no residues. Less than 1% of the chlorinated paraffins ingested were incorporated into the body (without head, feet, gut and feathers), whereas about 1.5% were eliminated with the egg yolk and 30% were excreted with urine and faeces. A six-week kinetic depuration study revealed a biphasic elimination with half-lifes of 4-40 min (liver, kidneys, legs, fat, blood) for the initial rapid phase, and 15-30 days (blood, fat, liver, yolk, kidneys, legs) for the terminal slow phase.
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USDA-ARS?s Scientific Manuscript database
Pneumonia is a population-limiting disease of bighorn sheep (BHS; Ovis canadensis) and a recognized disease entity in domestic sheep (DS; Ovis aries) worldwide. Respiratory disease in BHS lambs can persist for years after all-age outbreaks, resulting in suppressed lamb recruitment. It has been sugge...
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2008-03-01
throughout history where nerve agents have been used on human populations, such as the subway bombing in Tokyo and Matsumoto, Japan. Data can be...kidney, fat, diaphragm, arterial blood, venous blood, bronchial passages, and the skin. The remaining tissues will be lumped together as either slowly...were then further developed as a weapon, whose primary effect is on the central nervous system. These agents are tabun, sarin, soman, and VX. They
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Dissipation kinetics of bifenazate in tea under tropical conditions.
Satheshkumar, Annamalai; Senthurpandian, Velu Kalaipandian; Shanmugaselvan, Veilumuthu Anandham
2014-02-15
Field experiments were conducted during April and May of 2011 in Valparai, Coonoor and Gudalur (Tamil Nadu, India) to determine the residues of bifenazate in black tea. From this study, residue levels of bifenazate at different harvest intervals, persistence, dissipation pattern during processing, rate constant and half-life values were calculated. Residues of bifenazate dissipated exponentially after spraying and at Gudalur trial, on the 16th day after application residues were below the maximum residue level of 0.02 mg/kg set by the European Union. However, no residues were detected in the tea brew. Regression lines drawn for bifenazate showed that it followed first order dissipation kinetics. Half-life values varied from 1.03 to 1.36 days for bifenazate and a pre-harvest interval of 16 days is suggested. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing
2015-01-01
Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle.
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Hurtado, Ana; Sanchez, Isbene; Bastida, Felix; Minguijón, Esmeralda; Juste, Ramón A; García-Pérez, Ana L
2009-11-05
Border disease virus (BDV) causes important reproductive losses, and eradication strategies focus on the identification and removal of persistently infected animals arising after in uterine infection. BDV infection dynamics were studied in 13 ewes experimentally infected with BDV-4 genotype at 3 phases of pregnancy [days 108 (group A), 76 (group B) and 55 (group C)] by quantification of viral RNA in blood collected on days -1 to parturition using quantitative real-time RT-PCR (qRT-PCR). Viral RNA loads were also measured in blood/foetal fluid and tissue samples from their offspring at lambing (3 foetuses, 7 stillborns, 15 lambs). qRT-PCR results were compared with those obtained by conventional RT-PCR and used to predict persistent infections. Viral RNA was detected in the ewes between days 2-15 p.i. The viraemia reached its highest peak between days 6-7 p.i. with a second peak at days 11-12 p.i. qRT-PCR was significantly faster to perform (less than 1 h) than conventional RT-PCR and detected BDV RNA in more ewes, being detection more continuous and prolonged in time. The virus was detected in peripheral blood in a higher percentage of lambs than in tissues, where differences in viral genome copies were more marked. Skin and cerebral cortex showed the highest viral RNA loads, and spleen and spinal cord the lowest. High viral RNA loads were observed in several animals in group B and all in group C, infected during middle and early foetal development, respectively, but also in one lamb from group A, infected during late foetal development. Serology and viral genome copy number estimates in blood and tissues were used to establish a quantitative cut-off threshold for transient viraemia. Viral RNA quantification showed potential for the discrimination between persistent infections and transient viraemia using single-time point blood sampling and raised questions regarding foetal immune system development and the occurrence of persistent infections.
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Kwok, Hin; Chan, Koon Wing; Chan, Kwok Hung; Chiang, Alan Kwok Shing
2015-01-01
Our study aimed at investigating the distribution, persistence and interchange of viral strains among peripheral blood mononuclear cells (PBMC), plasma and saliva of primary Epstein-Barr virus (EBV) infection subjects. Twelve infectious mononucleosis (IM) patients and eight asymptomatic individuals (AS) with primary EBV infection were followed longitudinally at several time points for one year from the time of diagnosis, when blood and saliva samples were collected and separated into PBMC, plasma and saliva, representing circulating B cell, plasma and epithelial cell compartments, respectively. To survey the viral strains, genotyping assays for the natural polymorphisms in two latent EBV genes, EBNA2 and LMP1, were performed and consisted of real-time PCR on EBNA2 to distinguish type 1 and 2 viruses, fluorescent-based 30-bp typing assay on LMP1 to distinguish deletion and wild type LMP1, and fluorescent-based heteroduplex tracking assays on both EBNA2 and LMP1 to distinguish defined polymorphic variants. No discernible differences were observed between IM patients and AS. Multiple viral strains were acquired early at the start of infection. Stable persistence of dominant EBV strains in the same tissue compartment was observed throughout the longitudinal samples. LMP1-defined strains, China 1, China 2 and Mediterranean+, were the most common strains observed. EBNA2-defined groups 1 and 3e predominated the PBMC and saliva compartments. Concordance of EBNA2 and LMP1 strains between PBMC and saliva suggested ready interchange of viruses between circulating B cell and epithelial cell pools, whilst discordance of viral strains observed between plasma and PBMC/saliva indicated presence of viral pools in other undetermined tissue compartments. Taken together, the results indicated that the distribution, persistence and interchange of viral strains among the tissue compartments are more complex than those proposed by the current model of EBV life cycle. PMID:25807555
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Rapoport, Natalya; Gupta, Roohi; Kim, Yoo-Shin; O'Neill, Brian E
2015-05-28
Intravital imaging of nanoparticle extravasation and tumor accumulation has revealed, for the first time, detailed features of carrier and drug behavior in circulation and tissue that suggest new directions for optimization of drug nanocarriers. Using intravital fluorescent microscopy, the extent of the extravasation, diffusion in the tissue, internalization by tissue cells, and uptake by the RES system were studied for polymeric micelles, nanoemulsions, and nanoemulsion-encapsulated drug. Discrimination of vascular and tissue compartments in the processes of micelle and nanodroplet extravasation and tissue accumulation was possible. A simple 1-D continuum model was suggested that allowed discriminating between various kinetic regimes of nanocarrier (or released drug) internalization in tumors of various sizes and cell density. The extravasation and tumor cell internalization occurred much faster for polymeric micelles than for nanoemulsion droplets. Fast micelle internalization resulted in the formation of a perivascular fluorescent coating around blood vessels. A new mechanism of micelle extravasation and internalization was suggested, based on the fast extravasation and internalization rates of copolymer unimers while maintaining micelle/unimer equilibrium in the circulation. The data suggested that to be therapeutically effective, nanoparticles with high internalization rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentration gradients that induce drug resistance. However an extra-fast diffusion should be avoided as it may result in the flow of extravasated nanoparticles from the tumor to normal organs, which would compromise targeting efficiency. The extravasation kinetics were different for nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature release of some fraction of the drug from the carrier. In conclusion, the development of an "ideal" drug carrier should involve the optimization of both drug retention and carrier diffusion parameters. Copyright © 2015 Elsevier B.V. All rights reserved.
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Abdala Valencia, H; Loffredo, L F; Misharin, A V; Berdnikovs, S
2016-02-01
Eosinophil recruitment in asthma is a multistep process, involving both trans-endothelial migration to the lung interstitium and trans-epithelial migration into the airways. While the trans-endothelial step is well studied, trans-epithelial recruitment is less understood. To contrast eosinophil recruitment between these two compartments, we employed a murine kinetics model of asthma. Eosinophils were phenotyped by multicolor flow cytometry in digested lung tissue and bronchoalveolar lavage (BAL) simultaneously, 6 h after each ovalbumin (OVA) challenge. There was an early expansion of tissue eosinophils after OVA challenge followed by eosinophil buildup in both compartments and a shift in phenotype over the course of the asthma model. Gradual transition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) phenotype in lung tissue was associated with eosinophil recruitment to the airways, as all BAL eosinophils were of the latter phenotype. Secondary microarray analysis of tissue-activated eosinophils demonstrated upregulation of specific integrin and chemokine receptor signature suggesting interaction with the mucosa. Using adhesion assays, we demonstrated that integrin CD11c mediated adhesion of eosinophils to fibrinogen, a significant component of epithelial barrier repair and remodeling. To the best of our knowledge, this is the only report to date dissecting compartmentalization of eosinophil recruitment as it unfolds during allergic inflammation. By capturing the kinetics of eosinophil phenotypic change in both tissue and BAL using flow cytometry and sorting, we were able to demonstrate a previously undocumented association between phenotypic shift of tissue-recruited eosinophils and their trans-epithelial movement, which implicates the existence of a specific mechanism targeting these cells to mucosal airways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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[Persistence of the primordial vitreous body and buphthalmos].
Cernea, P; Simionescu, C; Bosun, I
1995-01-01
Persistence of the hyperplasic primordial vitreous body is determined by a deletion of embryonal development of the vitreous body and of the hyaloid vascular system. Infant aged 3.5 years presents persistence of primordial vitreous body with crystalline dislocation in the camera aquosa and secondary buphthalmos of the left eye and microphthalmos with dislocation of the crystalline in the vitreous body of the right eye. At the back of the right eye we noticed a whitish mass, richly vascularized with vestiges from the hyaloid artery, but the posterior half of the vitreous cavity is filled with microscopic blood; the fibrovascular membrane is made of conjunctive tissue set in parallel layers and vessels with macrolipophagic degeneration. Microscopic investigation of retina reveals glial hyperplasia zones in the neighbourhood of the vitreous body. In the present paper the authors show the persistence of the primordial vitreous body in the left eye and bilateral dislocation of the crystalline, revealing multiple ocular malformations.
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Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas
2013-08-01
While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats. Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals. Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals. [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.
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NASA Astrophysics Data System (ADS)
Shultz, Kimberly M.; Debreczeny, Martin P.; Dorshow, Richard B.; Keating, Jennifer E.; Bechtel, Kate L.
2017-02-01
The fluorescent tracer agent 3,6-diamino-2,5-bisN-[(1R)-1-carboxy-2-hydroxyethyl]carbamoylpyrazine, designated MB-102, is cleared from the body solely by the kidneys. A prototype noninvasive fluorescence detection device has been developed for monitoring transdermal fluorescence after bolus intravenous injection of MB-102 in order to measure kidney function. A mathematical model of the detected fluorescence signal was created for evaluation of observed variations in agent kinetics across body locations and for analysis of candidate instrument geometries. The model comprises pharmacokinetics of agent distribution within body compartments, local diffusion of the agent within the skin, Monte Carlo photon transport through tissue, and ray tracing of the instrument optics. Data from eight human subjects with normal renal function and a range of skin colors shows good agreement with simulated data. Body site dependence of equilibration kinetics was explored using the model to find the local vasculature-to-interstitial diffusion time constant, blood volume fraction, and interstitial volume fraction. Finally, candidate instrument geometries were evaluated using the model. While an increase in source-detector separation was found to increase sensitivity to tissue optical properties, it reduced the relative intensity of the background signal with minimal effect on the measured equilibration kinetics.
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PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling
Perfluoroalkyl acids (PFAAs) are ubiquitous and persistent environmental contaminants. Compounds such as perfluoroocanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) are readily found in the tissues of humans...
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Tunable long persistent luminescence in the second near-infrared window via crystal field control.
Nie, Jianmin; Li, Yang; Liu, Shanshan; Chen, Qiuqun; Xu, Qi; Qiu, Jianrong
2017-09-29
Construction of an active composite as a biomarker with deeper tissue penetration and higher signal-to-noise ratio (SNR) is of great importance for the application in bioimaging. Here, we report a strategy for tuning the emission bandwidth and intensity via crystal field control in long persistent phosphors (LPPs). Ni 2+ -doped Zn 1+y Sn y Ga 2-x-2y O 4 phosphors, with a tunable emission band peaking from 1270 to 1430 nm in the second near-infrared (NIR) window, have been successfully prepared. Such featured materials have the advantages of low absorption and scattering as well as more efficient tissue penetration. The emission spectra can be controlled by tailoring the local crystal field around the activator precisely via substitution of Zn and Sn for Ga. Moreover, with high resolution and weak light disturbance, these developed multi-band afterglow phosphors exhibit great application potential in advanced optical imaging.
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Jockusch, Steffen; Turro, Nicholas J; Banala, Srinivas; Kräutler, Bernhard
2014-02-01
Fluorescent chlorophyll catabolites (FCCs) are fleeting intermediates of chlorophyll breakdown, which is seen as an enzyme controlled detoxification process of the chlorophylls in plants. However, some plants accumulate large amounts of persistent FCCs, such as in senescent leaves and in peels of yellow bananas. The photophysical properties of such a persistent FCC (Me-sFCC) were investigated in detail. FCCs absorb in the near UV spectral region and show blue fluorescence (max at 437 nm). The Me-sFCC fluorescence had a quantum yield of 0.21 (lifetime 1.6 ns). Photoexcited Me-sFCC intersystem crosses into the triplet state (quantum yield 0.6) and generates efficiently singlet oxygen (quantum yield 0.59). The efficient generation of singlet oxygen makes fluorescent chlorophyll catabolites phototoxic, but might also be useful as a (stress) signal and for defense of the plant tissue against infection by pathogens.
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Flores-Ramírez, R; Espinosa-Reyes, G; Cilia-López, V G; González-Mille, D J; Rodríguez-Aguilar, M; Díaz de León-Martínez, L; Díaz-Barriga, F
2017-02-01
A simple and rapid focused ultrasound extraction method was developed for the determination of Persistent Organic Pollutants (POPs) in liver tissue obtained of giant toad (Rhinella marina) using a gas chromatography coupled to a mass detector with electron impact ionization. The performed method for POPs, was validated in fortified matrix, showing linearity from the LOQ up to 100 ng/mL; LODs and LOQs for each compound were between 1.7 and 4.8 and 3.5-7.5 ng/mL, respectively. Recovery rates were among 79%-116% for POPs determined. Finally, the method was applied in liver samples of giant toads found in a malarial area in Mexico. The sensitivity of the proposed method was good enough to ensure reliable determination of target analytes at concentration levels commonly found in this kind of samples.
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Otic Langerhans' Cell Histiocytosis in an Adult: A Case Report and Review of the Literature
Gungadeen, Anil; Kullar, Peter; Yates, Philip
2013-01-01
Objective. To present a case of otic Langerhans' cell histiocytosis in an adult. Also included the diagnosis and management of the condition and a review of the relevant literature. Case Report. We report a case of a 41-year-old man with a history of persistent unilateral ear discharge associated with an aural polyp. Radiological imaging showed bony lesions of the skull and a soft-tissue mass within the middle ear. Histological analysis of the polyp demonstrated Langerhans' cell histiocytosis. His otological symptoms were completely resolved with the systemic therapy. Conclusions. Otic Langerhans' cell histiocytosis can present in adults. Persistent ear symptoms along with evidence of soft-tissue masses within the ear and bony lesions of the skull or elsewhere should prompt the otolaryngologists to include Langerhans' cell histiocytosis in their differential diagnosis. Management should be with systemic therapy rather than local surgical treatment. PMID:23762704
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An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis
Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon
2011-01-01
Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment. PMID:22205850
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An adult case of chronic active Epstein-Barr virus infection with interstitial pneumonitis.
Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon; Peck, Kyong Ran
2011-12-01
Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.
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Macrophages in tissue repair, regeneration, and fibrosis
Wynn, Thomas A.; Vannella, Kevin M.
2016-01-01
Inflammatory monocytes and resident tissue macrophages are key regulators of tissue repair, regeneration, and fibrosis. Following tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, with uncontrolled inflammatory mediator and growth factor production, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contributing to a state of persistent injury, which may lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating phenotypes following injury, and highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically. PMID:26982353
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Kinetic modeling in PET imaging of hypoxia
Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas
2014-01-01
Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200
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Persistence of azoxystrobin in/on grapes and soil in different grapes growing areas of India.
Gajbhiye, Vijay Tularam; Gupta, Suman; Mukherjee, Irani; Singh, Shashi Bala; Singh, Neera; Dureja, Prem; Kumar, Yogesh
2011-01-01
Persistence of azoxystrobin was studied in/on grapes when applied @ 150 g ai ha⁻¹ (recommended dose) and 300 g ai ha⁻¹ (double the recommended dose) in three grapes growing states of India, namely Karnataka, Maharashtra and Tamil Nadu, in the year 2006-2007. A total of five sprays were given at an interval of about 15 days. Grapes and soil samples were collected after 5th spray, extracted and analysed by gas chromatography using electron capture detector. Half life of azoxystrobin on grapes varied from 5.4 to 11.2 days. Residues of azoxystrobin were much below the prescribed MRL (0.5 mg kg⁻¹) after 21 days. The dissipation of azoxystrobin in soil followed first order rate kinetics with an average half life of 8.1 days at the recommended dose of application.
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It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barcellos-Hoff, Mary Helen
How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises itsmore » ability to suppress carcinogenesis.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.
2015-07-01
Object kinetic Monte Carlo (OKMC) simulations have been performed to investigate various aspects of cascade aging in bulk tungsten and to determine the sensitivity of the results to the kinetic parameters. The primary focus is on how the kinetic parameters affect the initial recombination of defects in the first few ns of a simulation. The simulations were carried out using the object kinetic Monte Carlo (OKMC) code KSOME (kinetic simulations of microstructure evolution), using a database of cascades obtained from results of molecular dynamics (MD) simulations at various primary knock-on atom (PKA) energies and directions at temperatures of 300, 1025more » and 2050 K. The OKMC model was parameterized using defect migration barriers and binding energies from ab initio calculations. Results indicate that, due to the disparate mobilities of SIA and vacancy clusters in tungsten, annealing is dominated by SIA migration even at temperatures as high as 2050 K. For 100 keV cascades initiated at 300 K recombination is dominated by annihilation of large defect clusters. But for all other PKA energies and temperatures most of the recombination is due to the migration and rotation of small SIA clusters, while all the large SIA clusters escape the cubic simulation cell. The inverse U-shape behavior exhibited by the annealing efficiency as a function of temperature curve, especially for cascades of large PKA energies, is due to asymmetry in SIA and vacancy clustering assisted by the large difference in mobilities of SIAs and vacancies. This annealing behavior is unaffected by the dimensionality of SIA migration persists over a broad range of relative mobilities of SIAs and vacancies.« less
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Bearden, Shawn E
2007-09-01
Little is known of the vasomotor responses of skeletal muscle arterioles during and following muscle contraction. We hypothesized that aging leads to impaired arteriolar responses to muscle contraction and recovery. Nitric oxide (NO) availability, which is age dependent, has been implicated in components of these kinetics. Therefore, we also hypothesized that changes in the kinetics of vascular responses are associated with the NO pathway. Groups were young (3 mo), old (24 mo), endothelial NO synthase knockout (eNOS-/-), and N(G)-nitro-L-arginine (L-NA)-treated male and female C57BL/6 mice. The kinetics of vasodilation during and following 1 min of contractions of the gluteus maximus muscle were recorded in second-order (regional distribution) and third-order (local control) arterioles. Baseline, peak (during contraction), and maximal diameters (pharmacological) were not affected by age or sex. The kinetics of dilation and recovery were not different between males and females at the young age. There was a significant slowing of vasodilation at the onset of contractions (approximately 2-fold; P < 0.05) and a significant speeding of recovery ( approximately 5-fold; P < 0.05) in old males vs. old females and vs. young eNOS-/-, and L-NA did not affect the kinetics at the onset of muscle contraction. eNOS-/- mimicked the rapid recovery of old males in second-order arterioles; acute NO production (L-NA) explained approximately 50% of this effect. These data demonstrate fundamental age-related differences between the sexes in the dynamic function of skeletal muscle arterioles. Understanding how youthful function persists in females but not males may provide therapeutic insight into clinical interventions to maintain dynamic microvascular control of nutrient supply with age.
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Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.
Sag, Can M; Wolff, Hendrik A; Neumann, Kay; Opiela, Marie-Kristin; Zhang, Juqian; Steuer, Felicia; Sowa, Thomas; Gupta, Shamindra; Schirmer, Markus; Hünlich, Mark; Rave-Fränk, Margret; Hess, Clemens F; Anderson, Mark E; Shah, Ajay M; Christiansen, Hans; Maier, Lars S
2013-11-01
Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative stress and persistently activated CaMKII. Our findings suggest impaired cardiac myocytes Ca handling as a so far unknown mediator of IR-dependent cardiac damage that might be of relevance for radiation-induced cardiac dysfunction.
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Suetens, Annelies; Konings, Katrien; Moreels, Marjan; Quintens, Roel; Verslegers, Mieke; Soors, Els; Tabury, Kevin; Grégoire, Vincent; Baatout, Sarah
2016-01-01
The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy). PMID:27148479
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Smedra-Kaźmirska, Anna; Barzdo, Maciej; Kedzierski, Maciej; Szram, Stefan; Berent, Jarosław
2010-01-01
In Poland, according to the Weapons and Ammunition Act" an air weapon which has kinetic energy of fired projectiles below 17 J does not require registration and can be bought even on the Internet. Sport and recreational shooting with this weapon does not have to be performed in a special shooting-range, but can be carried on in an open terrain providing "particular caution" is exercised. In this study we presented experimental effects of shooting pneumatic weapons (Norica Dragon air-rifle and Walther PPK/S air-pistol) which had kinetic energy of fired projectiles below 17 J. The aim of this study was to assess the effects of shooting the above weapons at human soft tissues and thin bones of the temple region to empirically evaluate the degree of danger to health and life, which such shots can produce. We used 20% gelatine blocks at 10 degrees C, which were the model of human soft tissues, and fresh calf scapulas, which served as the models of the temporal bone of the human cranium. Before the experiment, we had evaluated the weight of all the projectiles and their initial velocity using a chronograph. By these measures, we calculated the kinetic energy of the fired missiles. After shooting, we estimated if projectiles of different shapes shot from air weapons characterized by different kinetic energy and from different distances penetrated the gelatine blocks and if the said missiles perforated the bones. We also measured the depth of missiles penetration in the gelatine blocks.
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Kawiecki, Anna B; Mayton, E Handly; Dutuze, M Fausta; Goupil, Brad A; Langohr, Ingeborg M; Del Piero, Fabio; Christofferson, Rebecca C
2017-04-18
The appearance of severe Zika virus (ZIKV) disease in the most recent outbreak has prompted researchers to respond through the development of tools to quickly characterize transmission and pathology. We describe here another such tool, a mouse model of ZIKV infection and pathogenesis using the MR766 strain of virus that adds to the growing body of knowledge regarding ZIKV kinetics in small animal models. We infected mice with the MR766 strain of ZIKV to determine infection kinetics via serum viremia. We further evaluated infection-induced lesions via histopathology and visualized viral antigen via immunohistochemical labeling. We also investigated the antibody response of recovered animals to both the MR766 and a strain from the current outbreak (PRVABC59). We demonstrate that the IRF3/7 DKO mouse is a susceptible, mostly non-lethal model well suited for the study of infection kinetics, pathological progression, and antibody response. Infected mice presented lesions in tissues that have been associated with ZIKV infection in the human population, such as the eyes, male gonads, and central nervous system. In addition, we demonstrate that infection with the MR766 strain produces cross-neutralizing antibodies to the PRVABC59 strain of the Asian lineage. This model provides an additional tool for future studies into the transmission routes of ZIKV, as well as for the development of antivirals and other therapeutics, and should be included in the growing list of available tools for investigations of ZIKV infection and pathogenesis.
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Phytoremediation of chlorpyrifos by Populus and Salix.
Lee, Keum Young; Strand, Stuart E; Doty, Sharon L
2012-01-01
Chlorpyrifos is one of the commonly used organophosphorus insecticides that are implicated in serious environmental and human health problems. To evaluate plant potential for uptake of chlorpyrifos, several plant species of poplar (Populus sp.) and willow (Salix sp.) were investigated. Chlorpyrifos was taken up from nutrient solution by all seven plant species. Significant amounts of chlorpyrifos accumulated in plant tissues, and roots accumulated higher concentrations of chlorpyrifos than did shoots. Chlorpyrifos did not persist in the plant tissues, suggesting further metabolism of chlorpyrifos in plant tissue. To our knowledge, this work represents the first report for phytoremediation of chlorpyrifos using poplar and willow plants.
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Epstein-Barr virus: a paradigm for persistent infection - for real and in virtual reality.
Thorley-Lawson, David A; Duca, Karen A; Shapiro, Michael
2008-04-01
The really interesting thing about herpesviruses is that they can establish lifelong persistant infections in immunocompetent hosts. At first glance, they would seem to have very different ways of doing this. Here we will use as a model our current understanding of how the human herpesvirus Epstein-Barr virus establishes and maintains such an infection. We apply information from a wide range of sources including laboratory experimentation, clinical observation, animal models and a new computer simulation. We propose that the detailed mechanisms for establishing infection are dependent on the virus and tissues involved, but the strategy is the same - to persist in a long-lived cell type where the virus is invisible to the immune system and nonpathogenic.
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Quantitative dynamic ¹⁸FDG-PET and tracer kinetic analysis of soft tissue sarcomas.
Rusten, Espen; Rødal, Jan; Revheim, Mona E; Skretting, Arne; Bruland, Oyvind S; Malinen, Eirik
2013-08-01
To study soft tissue sarcomas using dynamic positron emission tomography (PET) with the glucose analog tracer [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), to investigate correlations between derived PET image parameters and clinical characteristics, and to discuss implications of dynamic PET acquisition (D-PET). D-PET images of 11 patients with soft tissue sarcomas were analyzed voxel-by-voxel using a compartment tracer kinetic model providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Furthermore, standard uptake values (SUVs) in the early (2 min p.i.; SUVE) and late (45 min p.i.; SUVL) phases of the PET acquisition were obtained. The derived transfer rates K1, k2 and k3, along with the metabolic rate of (18)FDG (MRFDG) and the vascular fraction νp, was fused with the computed tomography (CT) images for visual interpretation. Correlations between D-PET imaging parameters and clinical parameters, i.e. tumor size, grade and clinical status, were calculated with a significance level of 0.05. The temporal uptake pattern of (18)FDG in the tumor varied considerably from patient to patient. SUVE peak was higher than SUVL peak for four patients. The images of the rate constants showed a systematic pattern, often with elevated intensity in the tumors compared to surrounding tissue. Significant correlations were found between SUVE/L and some of the rate parameters. Dynamic (18)FDG-PET may provide additional valuable information on soft tissue sarcomas not obtainable from conventional (18)FDG-PET. The prognostic role of dynamic imaging should be investigated.
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Wang, Fei; Kovacs, Mihaly; Hu, Aihua; Limouze, John; Harvey, Estelle V; Sellers, James R
2003-07-25
Besides driving contraction of various types of muscle tissue, conventional (class II) myosins serve essential cellular functions and are ubiquitously expressed in eukaryotic cells. Three different isoforms in the human myosin complement have been identified as non-muscle class II myosins. Here we report the kinetic characterization of a human non-muscle myosin IIB subfragment-1 construct produced in the baculovirus expression system. Transient kinetic data show that most steps of the actomyosin ATPase cycle are slowed down compared with other class II myosins. The ADP affinity of subfragment-1 is unusually high even in the presence of actin filaments, and the rate of ADP release is close to the steady-state ATPase rate. Thus, non-muscle myosin IIB subfragment-1 spends a significantly higher proportion of its kinetic cycle strongly attached to actin than do the muscle myosins. This feature is even more pronounced at slightly elevated ADP levels, and it may be important in carrying out the cellular functions of this isoform working in small filamentous assemblies.
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Characterizing the kinetics of suspended cylindrical particles by polarization measurements
NASA Astrophysics Data System (ADS)
Liao, Ran; Ou, Xueheng; Ma, Hui
2015-09-01
Polarization has promising potential to retrieve the information of the steady samples, such as tissues. However, for the fast changing sample such as the suspended algae in the water, the kinetics of the particles also influence the scattered polarization. The present paper will show our recent results to extract the information about the kinetics of the suspended cylindrical particles by polarization measurements. The sample is the aqueous suspension of the glass fibers stirred by a magnetic stirrer. We measure the scattered polarization of the fibers by use of a simultaneous polarization measurement system and obtain the time series of two orthogonal polarization components. By use of correlation analysis, we obtain the time parameters from the auto-correlation functions of the polarization components, and observe the changes with the stirring speeds. Results show that these time parameters indicate the immigration of the fibers. After discussion, we find that they may further characterize the kinetics, including the translation and rotation, of the glass fibers in the fluid field.
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ACCUMULATION OF PERCHLORATE IN TOBACCO PLANTS: DEVELOPMENT OF A PLANT KINETIC MODEL
Previous studies have shown that tobacco plants are tolerant of perchlorate and will accumulate perchlorate in plant tissues. This research determined the uptake, translocation, and accumulation of perchlorate in tobacco plants. Three hydroponics growth studies were completed u...
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Urciuolo, F; Garziano, A; Imparato, G; Panzetta, V; Fusco, S; Casale, C; Netti, P A
2016-01-29
The fabrication of functional tissue units is one of the major challenges in tissue engineering due to their in vitro use in tissue-on-chip systems, as well as in modular tissue engineering for the construction of macrotissue analogs. In this work, we aim to engineer dermal tissue micromodules obtained by culturing human dermal fibroblasts into porous gelatine microscaffold. We proved that such stromal cells coupled with gelatine microscaffolds are able to synthesize and to assemble an endogenous extracellular matrix (ECM) resulting in tissue micromodules, which evolve their biophysical features over the time. In particular, we found a time-dependent variation of oxygen consumption kinetic parameters, of newly formed ECM stiffness and of micromodules self-aggregation properties. As consequence when used as building blocks to fabricate larger tissues, the initial tissue micromodules state strongly affects the ECM organization and maturation in the final macrotissue. Such results highlight the role of the micromodules properties in controlling the formation of three-dimensional macrotissue in vitro, defining an innovative design criterion for selecting tissue-building blocks for modular tissue engineering.
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Stefanopoulos, P K; Filippakis, K; Soupiou, O T; Pazarakiotis, V C
2014-12-01
Firearm-related injuries are caused by a wide variety of weapons and projectiles. The kinetic energy of the penetrating projectile defines its ability to disrupt and displace tissue, whereas the actual tissue damage is determined by the mode of energy release during the projectile-tissue interaction and the particular characteristics of the tissues and organs involved. Certain projectile factors, namely shape, construction, and stability, greatly influence the rate of energy transfer to the tissues along the wound track. Two zones of tissue damage can be identified, the permanent cavity created by the passage of the bullet and a potential area of contused tissue surrounding it, produced mainly by temporary cavitation which is a manifestation of effective high-energy transfer to tissue. Due to the complex nature of these injuries, wound assessment and the type and extent of treatment required should be based on an understanding of the various mechanisms contributing to tissue damage. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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Surgical reduction of adipose tissue in the male Sprague-Dawley rat.
Kral, J G
1976-10-01
The lipostatic theory of regulation of adipose tissue mass was tested by a method for surgical reduction (adipectomy) of 24% of the total body fat of nonobese adult Sprague-Dawley rats, as judged from carcass analyses. The reduction persisted during an observation period of 12 wk without any evidence of altered food intake, weight gain, or compensatory hypertrophy or hyperplasia of adipose tissue compared with sham-operated controls. No changes were found in serum free fatty acids, glycerol, triglycerides, cholesterol, or insulin between adipectomized and control animals, implying an intact quantitative function of the remaining adipose tissue. It is concluded that the size of the adipocytes rather than the number is important for a presumed lipostatic regulation of adipose tissue mass in the adult male Sprague-Dawley rat.
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Mack, David L; Boulanger, Corinne A; Callahan, Robert; Smith, Gilbert H
2007-01-01
Introduction Int6 has been shown to be an interactive participant with the protein translation initiation complex eIF3, the COP9 signalosome and the regulatory lid of the 26S proteasome. Insertion of mouse mammary tumor virus into the Int6 locus creates a C-terminally truncated form of the protein. Expression of the truncated form of Int6 (Int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. In addition, decreased expression of Int6/eIF3e is observed in approximately one third of all human breast carcinomas. Methods To validate that Int6sh has transforming activity in vivo, a transgenic mouse model was designed using the whey acidic protein (Wap) promoter to target expression of truncated Int6 to differentiating alveolar epithelial cells in the mammary gland. Microarray analyses were performed on normal, premalignant and malignant WapInt6sh expressing tissues. Results Mammary tumors developed in 42% of WapInt6sh heterozygous parous females at an average age of 18 months. In WapInt6sh mice, the contralateral mammary glands from both tumorous and non-tumorous tissues contained widespread focal alveolar hyperplasia. Only 4% of WapInt6sh non-breeding females developed tumors by 2 years of age. The Wap promoter is active only during estrus in the mammary tissue of cycling non-pregnant mice. Microarray analyses of mammary tissues demonstrated that Int6sh expression in the alveolar tissue altered the mammary transcriptome in a specific manner that was detectable even in the first pregnancy. This Int6sh-specific transcriptome pattern subsequently persisted in both the Int6sh-expressing alveolar hyperplasia and mammary tumors. These observations are consistent with the conclusion that WapInt6sh-expressing alveolar cells survive involution following the cessation of lactation, and subsequently give rise to the mammary tumors that arise in aging multiparous females. Conclusion These observations provide direct in vivo evidence that mammary-specific expression of the Int6sh truncation leads to persistence of alveolar hyperplasia with the accompanying increased predisposition to mammary tumorigenesis. PMID:17626637
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Wang, Jack P.; Naik, Punith P.; Chen, Hsi-Chuan; Shi, Rui; Lin, Chien-Yuan; Liu, Jie; Shuford, Christopher M.; Li, Quanzi; Sun, Ying-Hsuan; Tunlaya-Anukit, Sermsawat; Williams, Cranos M.; Muddiman, David C.; Ducoste, Joel J.; Sederoff, Ronald R.; Chiang, Vincent L.
2014-01-01
We established a predictive kinetic metabolic-flux model for the 21 enzymes and 24 metabolites of the monolignol biosynthetic pathway using Populus trichocarpa secondary differentiating xylem. To establish this model, a comprehensive study was performed to obtain the reaction and inhibition kinetic parameters of all 21 enzymes based on functional recombinant proteins. A total of 104 Michaelis-Menten kinetic parameters and 85 inhibition kinetic parameters were derived from these enzymes. Through mass spectrometry, we obtained the absolute quantities of all 21 pathway enzymes in the secondary differentiating xylem. This extensive experimental data set, generated from a single tissue specialized in wood formation, was used to construct the predictive kinetic metabolic-flux model to provide a comprehensive mathematical description of the monolignol biosynthetic pathway. The model was validated using experimental data from transgenic P. trichocarpa plants. The model predicts how pathway enzymes affect lignin content and composition, explains a long-standing paradox regarding the regulation of monolignol subunit ratios in lignin, and reveals novel mechanisms involved in the regulation of lignin biosynthesis. This model provides an explanation of the effects of genetic and transgenic perturbations of the monolignol biosynthetic pathway in flowering plants. PMID:24619611
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Oeur, R Anna; Karton, Clara; Post, Andrew; Rousseau, Philippe; Hoshizaki, T Blaine; Marshall, Shawn; Brien, Susan E; Smith, Aynsley; Cusimano, Michael D; Gilchrist, Michael D
2015-08-01
Concussions typically resolve within several days, but in a few cases the symptoms last for a month or longer and are termed persistent postconcussive symptoms (PPCS). These persisting symptoms may also be associated with more serious brain trauma similar to subdural hematoma (SDH). The objective of this study was to investigate the head dynamic and brain tissue responses of injury reconstructions resulting in concussion, PPCS, and SDH. Reconstruction cases were obtained from sports medicine clinics and hospitals. All subjects received a direct blow to the head resulting in symptoms. Those symptoms that resolved in 9 days or fewer were defined as concussions (n = 3). Those with symptoms lasting longer than 18 months were defined as PPCS (n = 3), and 3 patients presented with SDHs (n = 3). A Hybrid III headform was used in reconstruction to obtain linear and rotational accelerations of the head. These dynamic response data were then input into the University College Dublin Brain Trauma Model to calculate maximum principal strain and von Mises stress. A Kruskal-Wallis test followed by Tukey post hoc tests were used to compare head dynamic and brain tissue responses between injury groups. Statistical significance was set at p < 0.05. A significant difference was identified for peak resultant linear and rotational acceleration between injury groups. Post hoc analyses revealed the SDH group had higher linear and rotational acceleration responses (316 g and 23,181 rad/sec(2), respectively) than the concussion group (149 g and 8111 rad/sec(2), respectively; p < 0.05). No significant differences were found between groups for either brain tissue measures of maximum principal strain or von Mises stress. The reconstruction of accidents resulting in a concussion with transient symptoms (low severity) and SDHs revealed a positive relationship between an increase in head dynamic response and the risk for more serious brain injury. This type of relationship was not found for brain tissue stress and strain results derived by finite element analysis. Future research should be undertaken using a larger sample size to confirm these initial findings. Understanding the relationship between the head dynamic and brain tissue response and the nature of the injury provides important information for developing strategies for injury prevention.
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Amuzie, Chidozie J.; Islam, Zahidul; Kim, Jae Kyung; Seo, Ji-Hyun; Pestka, James J.
2010-01-01
Intranasal exposure of mice to satratoxin G (SG), a macrocyclic trichothecene produced by the indoor air mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) of the nose and brain. The purpose of this study was to measure the kinetics of distribution and clearance of SG in the mouse. Following intranasal instillation of female C57B16 mice with SG (500 μg/kg bw), the toxin was detectable from 5 to 60 min in blood and plasma, with the highest concentrations, 30 and 19 ng/ml, respectively, being observed at 5 min. SG clearance from plasma was rapid and followed single-compartment kinetics (t1/2 = 20 min) and differed markedly from that of other tissues. SG concentrations were maximal at 15–30 min in nasal turbinates (480 ng/g), kidney (280 ng/g), lung (250 ng/g), spleen (200 ng/g), liver (140 ng/g), thymus (90 ng/g), heart (70 ng/g), olfactory bulb (14 ng/g), and brain (3 ng/g). The half-lives of SG in the nasal turbinate and thymus were 7.6 and 10.1 h, respectively, whereas in other organs, these ranged from 2.3 to 4.4 h. SG was detectable in feces and urine, but cumulative excretion over 5 days via these routes accounted for less than 0.3% of the total dose administered. Taken together, SG was rapidly taken up from the nose, distributed to tissues involved in respiratory, immune, and neuronal function, and subsequently cleared. However, a significant amount of the toxin was retained in the nasal turbinate, which might contribute to SG’s capacity to evoke OSN death. PMID:20466779
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Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism
Ganusov, Vitaly V.; Auerbach, Jeremy
2014-01-01
The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism. PMID:24830705
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Dissipation of chlorantraniliprole in tomato fruits and soil.
Malhat, Farag; Abdallah, Hend; Hegazy, Islam
2012-03-01
The main objective of this study was to understand the residue and persistence behaviour of new insecticide chlorantraniliprole in tomato fruit and soil samples. Its residue was analyzed by HPLC and it dissipated in tomato fruit and soil following first order kinetics. The results showed half life (t(1/2)) value of 3.30 and 3.66 days for chlorantraniliprole in tomato fruit and soil, respectively. According to maximum residue limit (MRL) the pre-harvest interval (PHI) of chlorantraniliprole on tomato was 8-days after the treatment.
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2010-06-01
disposable glass pipettes with a small piece of glass wool at the bottom. On top of the glass wool was placed 0.5 g of Florisil, and 0.5 g of neutral...particles have a relatively slow dissolution rate (Lynch et al. 2003). Sufficient hydrated lime to effect complete destruction of the RDX particle...K. Hatfield, and J. J. Delfino. 2003. An exploratory approach to modeling explosive compound persistence and flux using dissolution kinetics
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Observations of Hall Reconnection Physics Far Downstream of the X Line.
Mistry, R; Eastwood, J P; Haggerty, C C; Shay, M A; Phan, T D; Hietala, H; Cassak, P A
2016-10-28
Observations made using the Wind spacecraft of Hall magnetic fields in solar wind reconnection exhausts are presented. These observations are consistent with the generation of Hall fields by a narrow ion inertial scale current layer near the separatrix, which is confirmed with an appropriately scaled particle-in-cell simulation that shows excellent agreement with observations. The Hall fields are observed thousands of ion inertial lengths downstream from the reconnection X line, indicating that narrow regions of kinetic dynamics can persist extremely far downstream.
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1991-11-07
new area of opticAl sp,,ctroscopy of solids where truly unique single environments and quantum effects can be studied in detail. In the pentacene in p...observed. Until very recentlx, the reports of SMI) have concentrated on the crystalline system of pentacene in p-terphenyl. Owing to the complex physical...excessive PSIIB, pentacene in benzoi, acid, is described briefly. The advantages of the perylene in PF_. system become evident immediately when
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Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism
Pan, Youdong; Tian, Tian; Park, Chang Ook; Lofftus, Serena Y.; Mei, Shenglin; Liu, Xing; Luo, Chi; O’Malley, John T.; Gehad, Ahmed; Teague, Jessica E.; Divito, Sherrie J.; Fuhlbrigge, Robert; Puigserver, Pere; Krueger, James G.; Hotamisligil, Gökhan S.; Clark, Rachael A.; Kupper, Thomas S.
2017-01-01
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens1–4. However, the biological pathways that enable the long-term survival of TRM cells are obscure4,5. Here we show that mouse CD8+ TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8+ TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes. In vitro, CD8+ TRM cells, but not CD8+ TCM, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8+ TRM cells. The persistence of CD8+ TRM cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8+ TRM cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8+ TRM cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity. PMID:28219080
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A persistent mass: A case of aggressive Angiomyxoma of the vulva.
Brzezinska, B N; Clements, A E; Rath, K S; Reid, G C
2018-05-01
We present a case of aggressive angiomyxoma of the vulva. The patient presented with a persistent, enlarging vulvar mass, initially misdiagnosed as a Bartholin gland cyst. The patient underwent wide local excision, which resulted in total resection of the mass. Final pathology was consistent with aggressive angiomyxoma, a rare soft tissue tumor with a predilection for the female pelvis. Though rare, it is important to consider in the differential diagnosis of a pelvic mass, given the locally aggressive nature of this tumor and propensity for recurrence.
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Leontovich, Alexey A; Intine, Robert V; Sarras, Michael P
2016-01-01
Metabolic memory (MM) is defined as the persistence of diabetic (DM) complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of the DNA replication/DNA metabolism process group (with upregulation of the apex1, mcm2, mcm4, orc3, lig1, and dnmt1 genes) were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6-13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of the DNA replication/repair process group best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.
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Kuklin, Nelly A; Pancari, Gregory D; Tobery, Timothy W; Cope, Leslie; Jackson, Jesse; Gill, Charles; Overbye, Karen; Francis, Kevin P; Yu, Jun; Montgomery, Donna; Anderson, Annaliesa S; McClements, William; Jansen, Kathrin U
2003-09-01
Staphylococcal infections associated with catheter and prosthetic implants are difficult to eradicate and often lead to chronic infections. Development of novel antibacterial therapies requires simple, reliable, and relevant models for infection. Using bioluminescent Staphylococcus aureus, we have adapted the existing foreign-body and deep-wound mouse models of staphylococcal infection to allow real-time monitoring of the bacterial colonization of catheters or tissues. This approach also enables kinetic measurements of bacterial growth and clearance in each infected animal. Persistence of infection was observed throughout the course of the study until termination of the experiment at day 16 in a deep-wound model and day 21 in the foreign-body model, providing sufficient time to test the effects of antibacterial compounds. The usefulness of both animal models was assessed by using linezolid as a test compound and comparing bioluminescent measurements to bacterial counts. In the foreign-body model, a three-dose antibiotic regimen (2, 5, and 24 h after infection) resulted in a decrease in both luminescence and bacterial counts recovered from the implant compared to those of the mock-treated infected mice. In addition, linezolid treatment prevented the formation of subcutaneous abscesses, although it did not completely resolve the infection. In the thigh model, the same treatment regimen resulted in complete resolution of the luminescent signal, which correlated with clearance of the bacteria from the thighs.
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Liedert, Bernd; Pluim, Dick; Schellens, Jan; Thomale, Jürgen
2006-01-01
The anticancer drug cisplatin executes its cytotoxic activity via formation of intra- and interstrand crosslinks in DNA. The relative contribution of structurally defined cisplatin adducts to induce apoptosis and the cellular processing of these lesions is still poorly understood mostly due to the lack of sensitive analytical tools for in vivo studies. Here we describe a new method to establish and characterize monoclonal antibodies (Mab) for structurally defined DNA adducts. The two major reaction products of cisplatin, the guanine–guanine (Pt-[GG]) and adenine–guanine (Pt-[AG]) intrastrand crosslinks are recognized by Mab R-C18 and R-B3, respectively. Both antibodies were employed in an immuno-cytological assay allowing the quantification of drug-induced lesions in individual cell nuclei at clinically relevant doses. Analyzing various tissues of cisplatin-treated C57Bl/6 mice the accumulation of Pt-(GG) was highest in kidney tubular cells compared with 30, 50 and 90% lower levels in kidney stroma, liver and peripheral blood cells, respectively. Adduct kinetics revealed that wild type mouse cells remove up to 80% of the crosslinks in contrast to their complete persistence in nucleotide excision repair-deficient (XPC−/−) mice. The aptitude of the immunoassay for human molecular dosimetry studies was demonstrated by measuring adduct levels in tumor biopsies from patients treated with cisplatin. PMID:16571898
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Mechanisms of DNA Damage Response to Targeted Irradiation in Organotypic 3D Skin Cultures
Acheva, Anna; Ghita, Mihaela; Patel, Gaurang; Prise, Kevin M.; Schettino, Giuseppe
2014-01-01
DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2. PMID:24505255
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Basic MR relaxation mechanisms and contrast agent design.
De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean
2015-09-01
The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.
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"Basic MR Relaxation Mechanisms & Contrast Agent Design"
De León-Rodríguez, Luis M.; Martins, André F.; Pinho, Marco; Rofsky, Neil; Sherry, A. Dean
2015-01-01
The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we will detail the many important considerations when pursuing the design and use of MR contrast media. We will offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand based contrast agents. We will discuss the mechanisms involved in magnetic resonance relaxation in the context of probe design strategies. A brief description of currently available contrast agents will be accompanied by an in-depth discussion that highlights promising MRI contrast agents in development for future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847
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Attempts to revive Mycobacterium tuberculosis from 300-year-old human mummies.
Lemma, Eshetu; Zimhony, Oren; Greenblatt, Charles L; Koltunov, Viktoria; Zylber, María Inés; Vernon, Kim; Spigelman, Mark
2008-06-01
Environmental persistence of Mycobacterium tuberculosis is subject to speculation. However, the reality that infected postmortem tissues can be a danger to pathologists and embalmers has worrisome implications. A few experimental studies have demonstrated the organism's ability to withstand exposure to embalming fluid and formalin. Recently, a failure was reported in an attempt to resuscitate an original isolate of Robert Koch to determine the lifetime of the tubercle bacillus. The present study also considers a historical approach to determine persistence under favorable environmental conditions. It asks whether acid-fast forms observed in tissues of 300-year-old Hungarian mummies can be resuscitated. Finding organisms before the advent of antibiotics and pasteurization may yield valuable genetic information. Using various media modifications, as well as guinea pig inoculation, an attempt was made to culture these tissues for M. tuberculosis. In addition, a resuscitation-promoting factor, known to increase colony counts in high G+C bacteria, was applied to the cultures. Although an occasional PCR-positive sample was detected, no colonies of M. tuberculosis were obtained. Our results may indicate that the life span of the tubercle bacillus is less than a few hundred years, even though in the short run it can survive harsh chemical treatment.
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Yu, Qiang; Zhang, Ruiqi; Deng, Shubo; Huang, Jun; Yu, Gang
2009-03-01
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have increasingly attracted global concerns in recent years due to their global distribution, persistence, strong bioaccumulation and potential toxicity. The feasibility of using powder activated carbon (PAC), granular activated carbon (GAC) and anion-exchange resin (AI400) to remove PFOS and PFOA from water was investigated with regard to their sorption kinetics and isotherms. Sorption kinetic results show that the adsorbent size influenced greatly the sorption velocity, and both the GAC and AI400 required over 168h to achieve the equilibrium, much longer than 4h for the PAC. Two kinetic models were adopted to describe the experimental data, and the pseudo-second-order model well described the sorption of PFOS and PFOA on the three adsorbents. The sorption isotherms show that the GAC had the lowest sorption capacity both for PFOS and PFOA among the three adsorbents, while the PAC and AI400 possessed the highest sorption capacity of 1.04mmolg(-1) for PFOS and 2.92mmolg(-1) for PFOA according to the Langmuir fitting. Based on the sorption behaviors and the characteristics of the adsorbents and adsorbates, ion exchange and electrostatic interaction as well as hydrophobic interaction were deduced to be involved in the sorption, and some hemi-micelles and micelles possibly formed in the intraparticle pores.
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A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...
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A mathematical model for foreign body reactions in 2D.
Su, Jianzhong; Gonzales, Humberto Perez; Todorov, Michail; Kojouharov, Hristo; Tang, Liping
2011-02-01
The foreign body reactions are commonly referred to the network of immune and inflammatory reactions of human or animals to foreign objects placed in tissues. They are basic biological processes, and are also highly relevant to bioengineering applications in implants, as fibrotic tissue formations surrounding medical implants have been found to substantially reduce the effectiveness of devices. Despite of intensive research on determining the mechanisms governing such complex responses, few mechanistic mathematical models have been developed to study such foreign body reactions. This study focuses on a kinetics-based predictive tool in order to analyze outcomes of multiple interactive complex reactions of various cells/proteins and biochemical processes and to understand transient behavior during the entire period (up to several months). A computational model in two spatial dimensions is constructed to investigate the time dynamics as well as spatial variation of foreign body reaction kinetics. The simulation results have been consistent with experimental data and the model can facilitate quantitative insights for study of foreign body reaction process in general.
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NASA Astrophysics Data System (ADS)
Bentz, Brian Z.
Many human cancer cell types over-express folate receptors, and this provides an opportunity to develop targeted anti-cancer drugs. For these drugs to be effective, their kinetics must be well understood in vivo and in deep tissue where tumors occur. We demonstrate a method for imaging these parameters by incorporating a kinetic compartment model and fluorescence into optical diffusion tomography (ODT). The kinetics were imaged in a live mouse, and found to be in agreement with previous in vitro studies, demonstrating the validity of the method and its feasibility as an effective tool in preclinical drug development studies. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing and evaluation. We present new optical phantoms fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in heterogeneous or anatomically realistic geometries, as opposed to previous phantoms which were limited to simple shapes formed by molds or machining. Furthermore, we show that Mie theory can be used to design the optical properties to match a target tissue. The phantom fabrication methods are versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data. Applications of diffuse optical imaging in the operating theater have been limited in part due to computational burden. We present an approach for the fast localization of arteries in the roof of the mouth that has the potential to reduce complications. Furthermore, we use the extracted position information to fabricate a custom surgical guide using 3D printing that could protect the arteries during surgery. The resolution of ODT is severely limited by the attenuation of high spatial frequencies. We present a super-resolution method achieved through the point localization of fluorescent inhomogeneities in a tissue-like scattering medium, and examine the localization uncertainty numerically and experimentally. Furthermore, we show numerical results for the localization of multiple fluorescent inhomogeneities by distinguishing them based on temporal characteristics. Potential applications include imaging neuron activation in the brain.
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Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha
2014-01-01
Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors. PMID:24613635
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DISTRIBUTION OF CHIRAL PCBS IN SELECTED TISSUES IN THE LABORATORY RAT
Polychlorinated biphenyls (PCBs) were manufactured for a large number of technical applications including for use in transformers and capacitors. The widespread commercial utilization of PCBs and their persistence in the environment have resulted in their worldwide distribution. ...
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Infertility Research at the NICHD
... on this finding, visit PubMed ID: 21719000 . Previous experimental evidence has suggested a possible link between persistent ... in which uterine lining tissue grows out of control, including endometrial cancer and ... in all the groups whether or not women were treated with progestin ...
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Gene expression profiling in the lung and liver of PFOS-exposed mouse fetuses
The industrial surfactants perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants commonly found in the tissues of humans and wildlife. Both compounds are agonists of peroxisome proliferator-activated receptor α (PPARα) and...
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CONTAMINANT CONCENTRATIONS IN WHOLE-BODY FISH AND SHELLFISH FROM U.S. ESTUARIES
Persistent bioaccumulative and toxic (PBT) pollutants are chemical contaminants that pose risks to ecosystems and human health. For these reasons, available tissue contaminant data from the US EPA Environmental Monitoring and Assessment Program's National Coastal Assessment were...
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Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.
Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis
2017-05-01
Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.
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Ni, Shou-Qing; Cui, Qingjie; Zheng, Zhen
2014-01-01
As a new category of persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) have become ubiquitous global environmental contaminants. No literature is available on the aerobic biotransformation of decabromodiphenyl ether (BDE-209). Herein, we investigated the interaction of PBDEs with aerobic granular sludge. The results show that the removal of BDE-209 from wastewater is mainly via biosorption onto aerobic granular sludge. The uptake capacity increased when temperature, contact time, and sludge dosage increased or solution pH dropped. Ionic strength had a negative influence on BDE-209 adsorption. The modified pseudo first-order kinetic model was appropriate to describe the adsorption kinetics. Microbial debromination of BDE-209 did not occur during the first 30 days of operation. Further study found that aerobic microbial degradation of 4,4′-dibromodiphenyl ether happened with the production of lower BDE congeners. PMID:25009812
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Helpap, B; Bubendorf, L
2016-02-01
Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.
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Desorption kinetics of organic chemicals from albumin.
Krause, Sophia; Ulrich, Nadin; Goss, Kai-Uwe
2018-03-01
When present in blood, most chemicals tend to bind to the plasma protein albumin. For distribution into surrounding tissues, desorption from albumin is necessary, because only the unbound form of a chemical is assumed to be able to cross cell membranes. For metabolism of chemicals, the liver is a particularly important organ. One potentially limiting step for hepatic uptake of the chemicals is desorption from albumin, because blood passes the human liver within seconds. Desorption kinetics from albumin can thus be an important parameter for our pharmacokinetic and toxicokinetic understanding of chemicals. This work presents a dataset of measured desorption rate constants and reveals a possibility for their prediction. Additionally, the obtained extraction profiles directly indicate physiological relevance of desorption kinetics, because desorption of the test chemicals is still incomplete after time frames comparable to the residence time of blood in the liver.
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Sahneh, Faryad Darabi; Scoglio, Caterina M; Monteiro-Riviere, Nancy A; Riviere, Jim E
2015-01-01
To assess the impact of biocorona kinetics on expected tissue distribution of nanoparticles (NPs) across species. The potential fate of NPs in vivo is described through a simple and descriptive pharmacokinetic model using rate processes dependent upon basal metabolic rate coupled to dynamics of protein corona. Mismatch of time scales between interspecies allometric scaling and the kinetics of corona formation is potentially a fundamental issue with interspecies extrapolations of NP biodistribution. The impact of corona evolution on NP biodistribution across two species is maximal when corona transition half-life is close to the geometric mean of NP half-lives of the two species. While engineered NPs can successfully reach target cells in rodent models, the results may be different in humans due to the fact that the longer circulation time allows for further biocorona evolution.
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NASA Technical Reports Server (NTRS)
Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Theriot, Corey; Zalesak, Selina; Yeshitla, Samrawit; Williams, Kyle; Wu, Honglu; James, John T.
2014-01-01
The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.
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Dynamics of Tissue-Specific CD8+ T Cell Responses during West Nile Virus Infection.
Aguilar-Valenzuela, Renan; Netland, Jason; Seo, Young-Jin; Bevan, Michael J; Grakoui, Arash; Suthar, Mehul S
2018-05-15
The mouse model of West Nile virus (WNV), which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8 + T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR)-transgenic mouse with specificity for the immunodominant epitope in the WNV NS4B protein (here referred to as transgenic WNV-I mice). Using an adoptive-transfer model, we found that WNV-I CD8 + T cells behave similarly to endogenous CD8 + T cell responses, with an expansion phase in the periphery beginning around day 7 postinfection (p.i.) followed by a contraction phase through day 15 p.i. Through the use of in vivo intravascular immune cell staining, we determined the kinetics, expansion, and differentiation into effector and memory subsets of WNV-I CD8 + T cells within the spleen and brain. We found that red-pulp WNV-I CD8 + T cells were more effector-like than white-pulp WNV-I CD8 + T cells, which displayed increased differentiation into memory precursor cells. Within the central nervous system (CNS), we found that WNV-I CD8 + T cells were polyfunctional (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), displayed tissue-resident characteristics (CD69 + and CD103 + ), persisted in the brain through day 15 p.i., and reduced the viral burden within the brain. The use of these TCR-transgenic WNV-I mice provides a new resource to dissect the immunological mechanisms of CD8 + T cell-mediated protection during WNV infection. IMPORTANCE West Nile Virus (WNV) is the leading cause of mosquito-borne encephalitis worldwide. There are currently no approved therapeutics or vaccines for use in humans to treat or prevent WNV infection. CD8 + T cells are critical for controlling WNV replication and protecting against infection. Here, we present a comprehensive characterization of a novel TCR-transgenic mouse with specificity for the immunodominant epitope in the WNV NS4B protein. In this study, we determine the kinetics, proliferation, differentiation into effector and memory subsets, homing, and clearance of WNV in the CNS. Our findings provide a new resource to dissect the immunological mechanisms of CD8 + T cell-mediated protection during WNV infection. Copyright © 2018 American Society for Microbiology.
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Khoontawad, Jarinya; Pairojkul, Chawalit; Rucksaken, Rucksak; Pinlaor, Porntip; Wongkham, Chaisiri; Yongvanit, Puangrat; Pugkhem, Ake; Jones, Alun; Plieskatt, Jordan; Potriquet, Jeremy; Bethony, Jeffery; Pinlaor, Somchai; Mulvenna, Jason
2017-01-01
Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared with proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer. PMID:28232516
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Adeniran, Ismail; MacIver, David H; Garratt, Clifford J; Ye, Jianqiao; Hancox, Jules C; Zhang, Henggui
2015-01-01
Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2-3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients.
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Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I
2011-01-01
The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562
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Persistence of Precursor Waves in Two-dimensional Relativistic Shocks
DOE Office of Scientific and Technical Information (OSTI.GOV)
Iwamoto, Masanori; Amano, Takanobu; Hoshino, Masahiro
2017-05-01
We investigated the efficiency of coherent upstream large-amplitude electromagnetic wave emission via synchrotron maser instability in relativistic magnetized shocks using two-dimensional particle-in-cell simulations. We considered a purely perpendicular shock in an electron–positron plasma. The coherent wave emission efficiency was measured as a function of the magnetization parameter σ , which is defined as the ratio of the Poynting flux to the kinetic energy flux. The wave amplitude was systematically smaller than that observed in one-dimensional simulations. However, it continued to persist, even at a considerably low magnetization rate, where the Weibel instability dominated the shock transition. The emitted electromagnetic wavesmore » were sufficiently strong to disturb the upstream medium, and transverse filamentary density structures of substantial amplitude were produced. Based on this result, we discuss the possibility of the wakefield acceleration model to produce nonthermal electrons in a relativistic magnetized ion–electron shock.« less
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Stent Polymers: Do They Make a Difference?
Rizas, Konstantinos D; Mehilli, Julinda
2016-06-01
The necessity of polymers on drug-eluting stent (DES) platforms is dictated by the need of an adequate amount and optimal release kinetic of the antiproliferative drugs for achieving ideal DES performance. However, the chronic vessel wall inflammation related to permanent polymer persistence after the drug has been eluted might trigger late restenosis and stent thrombosis. Biodegradable polymers have the potential to avoid these adverse events. A variety of biodegradable polymer DES platforms have been clinically tested, showing equal outcomes with the standard-bearer permanent polymer DES within the first year of implantation. At longer-term follow-up, promising lower rates of stent thrombosis have been observed with the early generation biodegradable polymer DES platforms compared to first-generation DES. Whether this safety benefit still persists with newer biodegradable polymer DES generations against second-generation permanent polymer DES needs to be explored. © 2016 American Heart Association, Inc.
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Mao, Li; Liu, Yu-Xiang; Huang, Chun-Hua; Gao, Hui-Ying; Kalyanaraman, Balaraman; Zhu, Ben-Zhan
2015-07-07
The ubiquitous distribution coupled with their carcinogenicity has raised public concerns on the potential risks to both human health and the ecosystem posed by the halogenated aromatic compounds (XAr). Recently, advanced oxidation processes (AOPs) have been increasingly favored as an "environmentally-green" technology for the remediation of such recalcitrant and highly toxic XAr. Here, we show that AOPs-mediated degradation of the priority pollutant pentachlorophenol and all other XAr produces an intrinsic chemiluminescence that directly depends on the generation of the extremely reactive hydroxyl radicals. We propose that the hydroxyl radical-dependent formation of quinoid intermediates and electronically excited carbonyl species is responsible for this unusual chemiluminescence production. A rapid, sensitive, simple, and effective chemiluminescence method was developed to quantify trace amounts of XAr and monitor their real-time degradation kinetics. These findings may have broad biological and environmental implications for future research on this important class of halogenated persistent organic pollutants.
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Memoryless self-reinforcing directionality in endosomal active transport within living cells
NASA Astrophysics Data System (ADS)
Chen, Kejia; Wang, Bo; Granick, Steve
2015-06-01
In contrast to Brownian transport, the active motility of microbes, cells, animals and even humans often follows another random process known as truncated Lévy walk. These stochastic motions are characterized by clustered small steps and intermittent longer jumps that often extend towards the size of the entire system. As there are repeated suggestions, although disagreement, that Lévy walks have functional advantages over Brownian motion in random searching and transport kinetics, their intentional engineering into active materials could be useful. Here, we show experimentally in the classic active matter system of intracellular trafficking that Brownian-like steps self-organize into truncated Lévy walks through an apparent time-independent positive feedback such that directional persistence increases with the distance travelled persistently. A molecular model that allows the maximum output of the active propelling forces to fluctuate slowly fits the experiments quantitatively. Our findings offer design principles for programming efficient transport in active materials.
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Persistence of Azoxystrobin in/on Grapes and Soil in Different Grapes Growing Areas of India
Gajbhiye, Vijay Tularam; Gupta, Suman; Mukherjee, Irani; Singh, Shashi Bala; Singh, Neera; Kumar, Yogesh
2010-01-01
Persistence of azoxystrobin was studied in/on grapes when applied @ 150 g ai ha−1 (recommended dose) and 300 g ai ha−1 (double the recommended dose) in three grapes growing states of India, namely Karnataka, Maharashtra and Tamil Nadu, in the year 2006–2007. A total of five sprays were given at an interval of about 15 days. Grapes and soil samples were collected after 5th spray, extracted and analysed by gas chromatography using electron capture detector. Half life of azoxystrobin on grapes varied from 5.4 to 11.2 days. Residues of azoxystrobin were much below the prescribed MRL (0.5 mg kg−1) after 21 days. The dissipation of azoxystrobin in soil followed first order rate kinetics with an average half life of 8.1 days at the recommended dose of application. PMID:21153804
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Reynoso, E; Nesci, A; Allegretti, P; Criado, S; Biasutti, M A
2012-01-01
Amoxicillin (Amx) and cephalexin (Cfx) are β-lactam antibiotics widely used in human and veterinary medicine. Two points of interest surrounding these molecules are the photodegradation of the molecules and their microbiological implications, as well as the persistence and bioaccumulation in the environment which may cause resistance to bacterial strains. The kinetic and mechanistic aspects of the photosensitized degradation of Amx and Cfx have been studied in water at pH 7.4 and 10 by stationary and time-resolved methods. Kinetic evidence indicates that the Rose Bengal-sensitized photooxidation of Amx at pH 7.4 proceeds via O(2)((1)Δ(g)) and O(2•-) mechanisms while at pH 10 the degradation path occurs, principally, via O(2)((1)Δ(g)). For Cfx, this process is attributed to O(2)((1)Δ(g)) and O(2•-). Photoproducts, which arise from the addition of oxygen atoms and subsequent oxidation of the groups -CH(3) to -COOH, were detected. For both antibiotics the bacteriostatic activity decreases in parallel to their photodegradation. The results of this study could potentially help scientists to better understand and predict the photodegradability of these antibiotics on living organisms and in different environmental compartments.
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Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic Modeling.
Bakh, Naveed A; Bisker, Gili; Lee, Michael A; Gong, Xun; Strano, Michael S
2017-11-01
A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle.
Kanno, Toru; Ishihara, Ryoko; Hatama, Shinichi; Uchida, Ikuo
2018-05-18
A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Three colostrum-deprived Holstein calves were housed separately in individual rooms of a high-containment facility and inoculated with the BCoV strain Kumamoto/1/07. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Seroconversion and titer changes were validated by hemagglutination inhibition tests and neutralization tests. Among the samples, nasal discharge showed a higher viral positivity than feces, which seemed to be associated with positive detection in the plasma. These data demonstrate the existence of persistent infection of BCoV in the respiratory tissues of cattle.
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Bucy, Daniel; Pollard, Rachel; Nelson, Richard
2017-01-01
Radiofrequency (RF) parathyroid ablation is a noninvasive treatment for hyperparathyroidism in dogs. There are no published data assessing factors associated with RF parathyroid ablation success or failure in order to guide patient selection and improve outcome. The purpose of this retrospective analytical study was to determine whether imaging findings, biochemical data, or concurrent diseases were associated with RF heat ablation treatment failure. For inclusion in the study, dogs must have had a clinical diagnosis of primary hyperparathyroidism, undergone cervical ultrasound and RF ablation of abnormal parathyroid tissue, and must have had at least 3 months of follow-up information available following the date of ultrasound-guided parathyroid ablation. Dogs were grouped based on those with recurrent or persistent hypercalcemia and those without recurrent or persistent hypercalcemia following therapy. Parathyroid nodule size, thyroid lobe size, nodule location, and presence of concurrent disease were recorded. Recurrence of hypercalcemia occurred in 9/32 dogs that had ablation of abnormal parathyroid tissue (28%) and one patient had persistent hypercalcemia (3%) following parathyroid ablation. Nodule width (P = 0.036), height (P = 0.028), and largest cross-sectional area (P = 0.023) were larger in dogs that had recurrent or persistent hypercalcemia following ablation. Hypothyroidism was more common in dogs with recurrent disease (P = 0.044). Radiofrequency ablation was successful in 22/32 (69%) dogs. Larger parathyroid nodule size and/or concurrent hypothyroidism were associated with treatment failure in dogs that underwent ultrasound-guided RF parathyroid nodule ablation. © 2016 American College of Veterinary Radiology.
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Pathogenesis of duck circovirus genotype 1 in experimentally infected Pekin ducks.
Hong, Y-T; Kang, M; Jang, H-K
2018-05-17
Ducks infected with duck circovirus (DuCV) exhibit feathering disorder, growth retardation, and low body weight. The virus can induce immunosuppression and increase rates of infection caused by other pathogens. The purpose of the present study was to investigate the pathogenesis of DuCV in experimentally infected Pekin ducks. At postmortem examination, gross lesions were observed in the immune organs including bursa of Fabricius (BF), thymus, and spleen. Hemorrhage, lymphocytic depletion, necrosis, and degeneration were observed in the bursal tissues by histological examination. The TUNEL assay was performed with bursal tissue. There was a significant difference of the apoptosis rate between the negative and DuCV-infected ducks. The earliest time point for detection of DuCV DNA in sera, cloacal swabs, and organs was 1 wk post-infection (WPI). Viral shedding was persistent and detectable at the end of the experiment (10 WPI). The findings provide evidence that horizontal transmission and persistent infection are the characteristics of DuCV. The organ with the highest mean viral load was the spleen, followed by BF, cecal tonsil, lung, thymus, liver, and kidney. We successfully established an experimental DuCV genotype 1 (DuCV-1) infection in Pekin ducks and demonstrated the pathogenicity and persistence of DuCV-1. In conclusion, DuCV-1 caused extensive damage to the immune organs that may have resulted in immunosuppression. Pathobiological characteristics of DuCV-1 include systemic infection, persistent infection, and horizontal transmission. These features allow DuCV-1 to circulate more easily in farms and increase the susceptibility of ducks to other diseases.
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NASA Technical Reports Server (NTRS)
Rerat, A.
1995-01-01
When pigs were submitted to duodenal infusion of solutions containing a large percentage of small peptides (PEP) or free amino acids with the same pattern (AAL) amino acids appear in the portal blood more rapidly and more uniformly after infusion of PEP then after infusion of AAL, with the notable exception of methionine for which the opposite was true. These differences were lowered when a carbohydrate (maltose dextrin) was present in the solution, but nevertheless remained significant for the first hour after the infusion. The long-term (8-hour) uptake of free amino acids into the liver and the peripheral tissues differed in profile according to the nature of the duodenal infusion. Peripheral uptake was appreciably less well balanced after infusion of free amino acids (deficiency of threonine and phenylalanine) than after infusion of small peptides (deficiency of methionine). Accordingly, in the rat, under conditions of discontinuous enteral nutrition the mixture of small peptides was of greater nutritive value than the mixture of free amino acids. It thus appears that the absorption kinetics which results in important variations in the temporal distribution of free amino acids in the tissues may be at the origin of transitory imbalances in tissue amino acid uptake, and as a result of a lower nutritive value.
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Measuring functioning hepatocytes using Tc-99m galactosylneoglycoalbumin (Tc-NGA)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stadalnik, R.C.; Vera, D.R.; Quadro, R.E.
1984-01-01
Tc-NGA is a synthetic ligand which binds only to hepatic binding protein (HBP), a receptor found only in the liver. It exhibits the properties of high tissue specificity, affinity-dependent uptake, and dose-dependent uptake. Tc-NGA provides an opportunity to study the functioning hepatocyte. The authors evaluated the usefulness of this technique in patients with hepatitis and hepatoma. After intravenous administration of 5 mCi Tc-NGA, dynamic images were acquired for 30 minutes followed by static views. Estimates of HBP concentrations were obtained by kinetic analysis of blood and liver time-activity curves. Kinetic estimates (reduced chi-squares < 3.0) of HBP correlated well withmore » the clinical course and histology. For example, a patient with hepatoma whose calculated receptor population (functioning hepatocytes) was 3.0 +- 0.9 x 10/sup -7/ mole, which is the normal range, is doing well undergoing chemotherapy. Liver biopsy demonstrated normal liver tissue except for the hepatoma. Another patient with hepatoma who had a severely depressed receptor population, 1.2 +- 0.2 x 10/sup -8/ mole, expired one week after the study. Liver biopsy demonstrated practically no normal tissue. Thus, by means of a complementary, receptor radiopharmaceutical and mathematical model, one should be able to quantitatively follow hepatocyte function and predict response to a therapeutic regimen.« less
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Pharmacokinetics of tilmicosin in equine tissues and plasma.
Clark, C; Dowling, P M; Ross, S; Woodbury, M; Boison, J O
2008-02-01
The macrolide antibiotic tilmicosin has potential for treating bacterial respiratory tract infections in horses. A pharmacokinetic study evaluated the disposition of tilmicosin in the horse after oral (4 mg/kg) or subcutaneous (s.c.) (10 mg/kg) administration. Tilmicosin was not detected in equine plasma or tissues after oral administration at this dose. With s.c. injection, tilmicosin concentrations reached a maximum concentration of approximately 200 ng/mL in the plasma of the horses. Tilmicosin concentrations in plasma persisted with a mean residence time (MRT) of 19 h. Maximum tissue residue concentrations (C(max)) of tilmicosin measured in equine lung, kidney, liver and muscle tissues after s.c. administration were 2784, 4877, 1398, and 881 ng/g, respectively. The MRT of tilmicosin in these tissues was approximately 27 h. Subcutaneous administration of tilmicosin resulted in severe reactions at the injection sites.
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Persistent Topology and Metastable State in Conformational Dynamics
Chang, Huang-Wei; Bacallado, Sergio; Pande, Vijay S.; Carlsson, Gunnar E.
2013-01-01
The large amount of molecular dynamics simulation data produced by modern computational models brings big opportunities and challenges to researchers. Clustering algorithms play an important role in understanding biomolecular kinetics from the simulation data, especially under the Markov state model framework. However, the ruggedness of the free energy landscape in a biomolecular system makes common clustering algorithms very sensitive to perturbations of the data. Here, we introduce a data-exploratory tool which provides an overview of the clustering structure under different parameters. The proposed Multi-Persistent Clustering analysis combines insights from recent studies on the dynamics of systems with dominant metastable states with the concept of multi-dimensional persistence in computational topology. We propose to explore the clustering structure of the data based on its persistence on scale and density. The analysis provides a systematic way to discover clusters that are robust to perturbations of the data. The dominant states of the system can be chosen with confidence. For the clusters on the borderline, the user can choose to do more simulation or make a decision based on their structural characteristics. Furthermore, our multi-resolution analysis gives users information about the relative potential of the clusters and their hierarchical relationship. The effectiveness of the proposed method is illustrated in three biomolecules: alanine dipeptide, Villin headpiece, and the FiP35 WW domain. PMID:23565139
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PHYTOREMEDIATION OF CHLORPYRIFOS BY POPULUS AND SALIX
Young Lee, Keum; Strand, Stuart E.; Doty, Sharon L.
2012-01-01
Chlorpyrifos is one of the commonly used organophosphorus insecticides that are implicated in serious environmental and human health problems. To evaluate plant potential for uptake of chlorpyrifos, several plant species of poplar (Populus sp.) and willow (Salix sp.) were investigated. Chlorpyrifos was taken up from nutrient solution by all seven plant species. Significant amounts of chlorpyrifos accumulated in plant tissues, and roots accumulated higher concentrations of chlorpyrifos than did shoots. Chlorpyrifos did not persist in the plant tissues, suggesting further metabolism of chlorpyrifos in plant tissue. To our knowledge, this work represents the first report for phytoremediation of chlorpyrifos using poplar and willow plants. PMID:22567694
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Direct measurement of catalase activity in living cells and tissue biopsies
DOE Office of Scientific and Technical Information (OSTI.GOV)
Scaglione, Christine N.; Xu, Qijin; Ramanujan, V. Krishnan, E-mail: Ramanujanv@csmc.edu
Spatiotemporal regulation of enzyme-substrate interactions governs the decision-making steps in biological systems. Enzymes, being functional units of every living cell, contribute to the macromolecular stability of cell survival, proliferation and hence are vital windows to unraveling the biological complexity. Experimental measurements capturing this dynamics of enzyme-substrate interactions in real time add value to this understanding. Furthermore these measurements, upon validation in realistic biological specimens such as clinical biopsies – can further improve our capability in disease diagnostics and treatment monitoring. Towards this direction, we describe here a novel, high-sensitive measurement system for measuring diffusion-limited enzyme-substrate kinetics in real time. Usingmore » catalase (enzyme) and hydrogen peroxide (substrate) as the example pair, we demonstrate that this system is capable of direct measurement of catalase activity in vitro and the measured kinetics follows the classical Michaelis-Menten reaction kinetics. We further demonstrate the system performance by measuring catalase activity in living cells and in very small amounts of liver biopsies (down to 1 μg total protein). Catalase-specific enzyme activity is demonstrated by genetic and pharmacological tools. Finally we show the clinically-relevant diagnostic capability of our system by comparing the catalase activities in liver biopsies from young and old mouse (liver and serum) samples. We discuss the potential applicability of this system in clinical diagnostics as well as in intraoperative surgical settings. - Highlights: • A novel, direct measurement of Catalase enzyme activity via, oxygen sensing method. • Steady-stateprofiles of Catalase activity follow the Michaelis-Menten Kinetics. • Catalase-specific activity demonstrated using genetic and pharmacological tools. • Overcomes limitations of spectroscopic methods and indirect calorimetric approaches. • Clear demonstration of the applicability in cancer cells and aging animal tissues.« less
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Pendlington, Ruth U; Minter, Helen J; Stupart, Leanne; MacKay, Cameron; Roper, Clive S; Sanders, David J; Pease, Camilla K
2008-01-01
In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.
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Henthorn, Thomas K; Avram, Michael J; Dahan, Albert; Gustafsson, Lars L; Persson, Jan; Krejcie, Tom C; Olofsen, Erik
2018-05-16
The pharmacokinetics of infused drugs have been modeled without regard for recirculatory or mixing kinetics. We used a unique ketamine dataset with simultaneous arterial and venous blood sampling, during and after separate S(+) and R(-) ketamine infusions, to develop a simplified recirculatory model of arterial and venous plasma drug concentrations. S(+) or R(-) ketamine was infused over 30 min on two occasions to 10 healthy male volunteers. Frequent, simultaneous arterial and forearm venous blood samples were obtained for up to 11 h. A multicompartmental pharmacokinetic model with front-end arterial mixing and venous blood components was developed using nonlinear mixed effects analyses. A three-compartment base pharmacokinetic model with additional arterial mixing and arm venous compartments and with shared S(+)/R(-) distribution kinetics proved superior to standard compartmental modeling approaches. Total pharmacokinetic flow was estimated to be 7.59 ± 0.36 l/min (mean ± standard error of the estimate), and S(+) and R(-) elimination clearances were 1.23 ± 0.04 and 1.06 ± 0.03 l/min, respectively. The arm-tissue link rate constant was 0.18 ± 0.01 min and the fraction of arm blood flow estimated to exchange with arm tissue was 0.04 ± 0.01. Arterial drug concentrations measured during drug infusion have two kinetically distinct components: partially or lung-mixed drug and fully mixed-recirculated drug. Front-end kinetics suggest the partially mixed concentration is proportional to the ratio of infusion rate and total pharmacokinetic flow. This simplified modeling approach could lead to more generalizable models for target-controlled infusions and improved methods for analyzing pharmacokinetic-pharmacodynamic data.
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Vignesh, Pandiarajan; Bhattad, Sagar; Shandilya, Jitendra-Kumar; Vyas, Sameer; Garg, Rashi; Rawat, Amit
2016-09-01
Vertebral osteomyelitis is known to occur in chronic granulomatous disease, a phagocytic disorder and the etiology is usually a fungus. Indolent spread of fungal infection from lungs to adjacent ribs and vertebra often results in persistent pneumonia and vertebral deformities. We report a 4-year-old boy with chronic cough and kyphosis, who had a fungal vertebral osteomyelitis and Acinetobacter spp. paravertebral soft tissue infection related to X-linked chronic granulomatous disease.
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Varrone, Andrea; Gulyás, Balázs; Takano, Akihiro; Stabin, Michael G; Jonsson, Cathrine; Halldin, Christer
2012-02-01
[(18)F]FE-PE2I is a promising dopamine transporter (DAT) radioligand. In nonhuman primates, we examined the accuracy of simplified quantification methods and the estimates of radiation dose of [(18)F]FE-PE2I. In the quantification study, binding potential (BP(ND)) values previously reported in three rhesus monkeys using kinetic and graphical analyses of [(18)F]FE-PE2I were used for comparison. BP(ND) using the cerebellum as reference region was obtained with four reference tissue methods applied to the [(18)F]FE-PE2I data that were compared with the kinetic and graphical analyses. In the whole-body study, estimates of adsorbed radiation were obtained in two cynomolgus monkeys. All reference tissue methods provided BP(ND) values within 5% of the values obtained with the kinetic and graphical analyses. The shortest imaging time for stable BP(ND) estimation was 54 min. The average effective dose of [(18)F]FE-PE2I was 0.021 mSv/MBq, similar to 2-deoxy-2-[(18)F]fluoro-d-glucose. The results in nonhuman primates suggest that [(18)F]FE-PE2I is suitable for accurate and stable DAT quantification, and its radiation dose estimates would allow for a maximal administered radioactivity of 476 MBq in human subjects. Copyright © 2012 Elsevier Inc. All rights reserved.
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Evaluation of the persistence of vaccine-induced protection with human vaccines.
Vidor, E
2010-01-01
The persistence of protection induced by vaccines is a key aspect of the implementation of human vaccination policies, particularly for ageing populations. At the time of initial licensure, the duration of protection induced by a vaccine is generally only documented by longitudinal follow up of cohorts of subjects enrolled in the pre-licensure trials over a period of 1-5 years. The follow up of these cohorts provides two types of data: antibody kinetics (or another clinically relevant immunological parameter) over time and the disease incidence. Generally, the latter trials, if implemented during the pre-licensure period, are designed to follow-up cohorts in order to demonstrate vaccine efficacy above the minimal level required for the license. For vaccines already licensed, additional tools exist. The use of immunological surrogate markers of protection is a practical way to monitor the duration of protection. Measuring the persistence of circulating antibodies is widely used in human vaccines. For several vaccines, observed data have allowed the creation of mathematical models to predict the antibody persistence over periods of time longer than those effectively documented. Clinical trials assessing the capacity of the immune system to mount a quick anamnestic response upon re-stimulation a long time after initial priming (measurement of immune memory) is also a tool employed to document the duration of protection. The waning of protection can also be demonstrated by an increase of disease incidence in the subsequent 'time-to-last-vaccine administration' age segments. Seroprevalence studies in a given age group of people that were vaccinated under real-life conditions are another way to document the persistence of protection. Finally, case-control studies in outbreak situations or in situations of persisting endemicity can also be used to document the persistence of the vaccine efficacy. All of these tools are used in the development of new vaccines, and also during their use in the field, in order to develop the best (re)vaccination policies. Copyright 2009 Elsevier Ltd. All rights reserved.
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Mukherjee, Irani; Kumar, Ashok; Kumar, Aman
2015-09-01
Persistence of delltamethrin, endosulfan, and triazophos in egg plant and tomato was studied following application of two ready mix formulations of insecticides viz. deltametrhin and endosulfan (Cobra 5000; 0.75% deltamethrin + 29.5% endosulfan) and deltamethrin and triazophos (Annaconda Plus; 1% deltamethrin + 35% triazophos) at recommended (1.0 L/ha and double dose 2.0 L/ha). The residues of deltamethrin persisted till 7 and 5 days in tomato and egg plant fruits, respectively, in the ready mix formulation of Cobra 5000 whereas endosulfan persisted till 15 and 10 days in tomato and egg plant fruits, respectively. Dissipation of the insecticides followed first-order kinetics with half-life values of deltamethrin and endosulfan ranged from 2.6 to 4.7 and 1.4 to 1.7 days, respectively, for both the vegetables. In case of combination mix of deltamethrin and triazophos (Annaconda Plus), deltamethrin persisted beyond 5 days in both tomato and egg plant fruits, while triazophos persisted till 10 days in both the vegetables. Residues of deltamethrin and triazophos dissipated with half-life of 2.6-4.2 and 1.7-4.1 days, respectively, on tomato and egg plant fruits. Based on the Codex MRL limits, a safe waiting period of 5 and 3 days is suggested for tomato and egg plant, respectively, for the ready mix formulation of deltamethrin and endosulfan (Cobra 5000), and 5-day waiting period is suggested for tomato and egg plant for the combination mix of deltamethrin and triazophos.
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Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak
2018-01-01
Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271
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Bergin, Ingrid L.; Wilding, Laura A.; Morishita, Masako; Walacavage, Kim; Ault, Andrew P.; Axson, Jessica L.; Stark, Diana I.; Hashway, Sara A.; Capracotta, Sonja S.; Leroueil, Pascale R.; Maynard, Andrew D.; Philbert, Martin A.
2015-01-01
Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity. PMID:26305411
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Hawe, David; Hernández Fernández, Francisco R; O'Suilleabháin, Liam; Huang, Jian; Wolsztynski, Eric; O'Sullivan, Finbarr
2012-05-01
In dynamic mode, positron emission tomography (PET) can be used to track the evolution of injected radio-labelled molecules in living tissue. This is a powerful diagnostic imaging technique that provides a unique opportunity to probe the status of healthy and pathological tissue by examining how it processes substrates. The spatial aspect of PET is well established in the computational statistics literature. This article focuses on its temporal aspect. The interpretation of PET time-course data is complicated because the measured signal is a combination of vascular delivery and tissue retention effects. If the arterial time-course is known, the tissue time-course can typically be expressed in terms of a linear convolution between the arterial time-course and the tissue residue. In statistical terms, the residue function is essentially a survival function - a familiar life-time data construct. Kinetic analysis of PET data is concerned with estimation of the residue and associated functionals such as flow, flux, volume of distribution and transit time summaries. This review emphasises a nonparametric approach to the estimation of the residue based on a piecewise linear form. Rapid implementation of this by quadratic programming is described. The approach provides a reference for statistical assessment of widely used one- and two-compartmental model forms. We illustrate the method with data from two of the most well-established PET radiotracers, (15)O-H(2)O and (18)F-fluorodeoxyglucose, used for assessment of blood perfusion and glucose metabolism respectively. The presentation illustrates the use of two open-source tools, AMIDE and R, for PET scan manipulation and model inference.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.
The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated withmore » biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.« less
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DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts.
Ahmed, Emad A; Vélaz, Eukene; Rosemann, Michael; Gilbertz, Klaus-P; Scherthan, Harry
2017-03-01
Noncycling and terminally differentiated (TD) cells display differences in radiosensitivity and DNA damage response. Unlike other TD cells, Sertoli cells express a mixture of proliferation inducers and inhibitors in vivo and can reenter the cell cycle. Being in a G 1 -like cell cycle stage, TD Sertoli cells are expected to repair DSBs by the error-prone nonhomologous end-joining pathway (NHEJ). Recently, we have provided evidence for the involvement of Ku-dependent NHEJ in protecting testis cells from DNA damage as indicated by persistent foci of the DNA double-strand break (DSB) repair proteins phospho-H2AX, 53BP1, and phospho-ATM in TD Sertoli cells of Ku70-deficient mice. Here, we analyzed the kinetics of 53BP1 foci induction and decay up to 12 h after 0.5 Gy gamma irradiation in DNA-PKcs-deficient (Prkdc scid ) and wild-type Sertoli cells. In nonirradiated mice and Prkdc scid Sertoli cells displayed persistent DSBs foci in around 12 % of cells and a fivefold increase in numbers of these DSB DNA damage-related foci relative to the wild type. In irradiated mice, Prkdc scid Sertoli cells showed elevated levels of DSB-indicating foci in 82 % of cells 12 h after ionizing radiation (IR) exposure, relative to 52 % of irradiated wild-type Sertoli cells. These data indicate that Sertoli cells respond to and repair IR-induced DSBs in vivo, with repair kinetics being slow in the wild type and inefficient in Prkdc scid . Applying the same dose of IR to Prdkc -/- and Ku -/- mouse embryonic fibroblast (MEF) cells revealed a delayed induction of 53BP1 DSB-indicating foci 5 min post-IR in Prdkc -/- cells. Inefficient DSB repair was evident 7 h post-IR in DNA-PKcs-deficient cells, but not in Ku -/- MEFs. Our data show that quiescent Sertoli cells repair genotoxic DSBs by DNA-PKcs-dependent NEHJ in vivo with a slower kinetics relative to somatic DNA-PKcs-deficient cells in vitro, while DNA-PKcs deficiency caused inefficient DSB repair at later time points post-IR in both conditions. These observations suggest that DNA-PKcs contributes to the fast and slow repair of DSBs by NHEJ.
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Iriarte, Fanny B; Obradović, Aleksa; Wernsing, Mine H; Jackson, Lee E; Balogh, Botond; Hong, Jason A; Momol, M Timur; Jones, Jeffrey B; Vallad, Gary E
2012-10-01
Soil-based root applications and attenuated bacterial strains were evaluated as means to enhance bacteriophage persistence on plants for bacterial disease control. In addition, the systemic nature of phage applied to tomato roots was also evaluated. Several experiments were conducted applying either single phages or phage mixtures specific for Ralstonia solanacearum , Xanthomonas perforans or X. euvesicatoria to soil surrounding tomato plants and measuring the persistence and translocation of the phages over time. In general, all phages persisted in the roots of treated plants and were detected in stems and leaves; although phage level varied and persistence in stems and leaves was at a much lower level compared with persistence in roots. Bacterial wilt control was typically best if the phage or phage mixtures were applied to the soil surrounding tomatoes at the time of inoculation, less effective if applied 3 days before inoculation, and ineffective if applied 3 days after inoculation. The use of an attenuated X. perforans strain was also evaluated to improve the persistence of phage populations on tomato leaf surfaces. In greenhouse and field experiments, foliar applications of an attenuated mutant X. perforans 91-118:∆ OPGH strain prior to phage applications significantly improved phage persistence on tomato foliage compared with untreated tomato foliage. Both the soil-based bacteriophage delivery and the use of attenuated bacterial strains improved bacteriophage persistence on respective root and foliar tissues, with evidence of translocation with soil-based bacteriophage applications. Both strategies could lead to improved control of bacterial pathogens on plants.
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Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.
Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine
2014-12-01
Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
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PERSISTENT ARM PAIN IS DISTINCT FROM PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY
Langford, Dale J.; Paul, Steven M.; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D.; Hamolsky, Deborah; Luce, Judith A.; Kober, Kord M.; Neuhaus, John M.; Cooper, Bruce A.; Aouizerat, Bradley E.; Miaskowski, Christine
2014-01-01
Persistent pain following breast cancer surgery is well-documented. However, it is not well characterized in terms of the anatomic site effected (i.e., breast, arm). In two separate growth mixture modeling analyses, we identified subgroups of women (n=398) with distinct breast pain and arm pain trajectories. Based on the fact that these latent classes differed by anatomic site, types if tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. Purposes of this companion study were to identify demographic and clinical characteristics that differed between the two arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection (ALND) sites, pain qualities, pain interference, and hand and arm function; as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the Moderate Arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and ALND site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. Perspective: For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. PMID:25439319
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NASA Astrophysics Data System (ADS)
Deng, Dongdong; Murphy, Michael J.; Hakim, Joe B.; Franceschi, William H.; Zahid, Sohail; Pashakhanloo, Farhad; Trayanova, Natalia A.; Boyle, Patrick M.
2017-09-01
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing morbidity and mortality in millions worldwide. The atria of patients with persistent AF (PsAF) are characterized by the presence of extensive and distributed atrial fibrosis, which facilitates the formation of persistent reentrant drivers (RDs, i.e., spiral waves), which promote fibrillatory activity. Targeted catheter ablation of RD-harboring tissues has shown promise as a clinical treatment for PsAF, but the outcomes remain sub-par. Personalized computational modeling has been proposed as a means of non-invasively predicting optimal ablation targets in individual PsAF patients, but it remains unclear how RD localization dynamics are influenced by inter-patient variability in the spatial distribution of atrial fibrosis, action potential duration (APD), and conduction velocity (CV). Here, we conduct simulations in computational models of fibrotic atria derived from the clinical imaging of PsAF patients to characterize the sensitivity of RD locations to these three factors. We show that RDs consistently anchor to boundaries between fibrotic and non-fibrotic tissues, as delineated by late gadolinium-enhanced magnetic resonance imaging, but those changes in APD/CV can enhance or attenuate the likelihood that an RD will anchor to a specific site. These findings show that the level of uncertainty present in patient-specific atrial models reconstructed without any invasive measurements (i.e., incorporating each individual's unique distribution of fibrotic tissue from medical imaging alongside an average representation of AF-remodeled electrophysiology) is sufficiently high that a personalized ablation strategy based on targeting simulation-predicted RD trajectories alone may not produce the desired result.
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Galbiati, Alessandro; Beauséjour, Christian; d'Adda di Fagagna, Fabrizio
2017-04-01
The DNA damage response (DDR) arrests cell cycle progression until DNA lesions, like DNA double-strand breaks (DSBs), are repaired. The presence of DSBs in cells is usually detected by indirect techniques that rely on the accumulation of proteins at DSBs, as part of the DDR. Such detection may be biased, as some factors and their modifications may not reflect physical DNA damage. The dependency on DDR markers of DSB detection tools has left questions unanswered. In particular, it is known that senescent cells display persistent DDR foci, that we and others have proposed to be persistent DSBs, resistant to endogenous DNA repair activities. Others have proposed that these peculiar DDR foci might not be sites of damaged DNA per se but instead stable chromatin modifications, termed DNA-SCARS. Here, we developed a method, named 'DNA damage in situ ligation followed by proximity ligation assay' (DI-PLA) for the detection and imaging of DSBs in cells. DI-PLA is based on the capture of free DNA ends in fixed cells in situ, by ligation to biotinylated double-stranded DNA oligonucleotides, which are next recognized by antibiotin anti-bodies. Detection is enhanced by PLA with a partner DDR marker at the DSB. We validated DI-PLA by demonstrating its ability to detect DSBs induced by various genotoxic insults in cultured cells and tissues. Most importantly, by DI-PLA, we demonstrated that both senescent cells in culture and tissues from aged mammals retain true unrepaired DSBs associated with DDR markers. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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Huang, Cong; Niethammer, Philipp
2018-05-15
Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A 2 (cPla 2 ), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.
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AN EFFICIENT TREATMENT STRATEGY FOR HISTOTRIPSY BY REMOVING CAVITATION MEMORY
Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.
2012-01-01
Cavitation memory effects occur when remnants of cavitation bubbles (nuclei) persist in the host medium and act as seeds for subsequent events. In pulsed cavitational ultrasound therapy, or histotripsy, this effect may cause cavitation to repeatedly occur at these seeded locations within a target volume, producing inhomogeneous tissue fractionation or requiring an excess number of pulses to completely homogenize the target volume. We hypothesized that by removing the cavitation memory, i.e., the persistent nuclei, the cavitation bubbles could be induced at random locations in response to each pulse; therefore, complete disruption of a tissue volume may be achieved with fewer pulses. To test the hypothesis, the cavitation memory was passively removed by increasing the intervals between successive pulses, Δt, from 2, 10, 20, 50 and 100, to 200 ms. Histotripsy treatments were performed in red blood cell tissue phantoms and ex vivo livers using 1-MHz ultrasound pulses of 10 cycles at P−/P+ pressure of 21/59 MPa. The phantom study allowed for direct visualization of the cavitation patterns and the lesion development process in real time using high-speed photography; the ex vivo tissue study provided validation of the memory effect in real tissues. Results of the phantom study showed an exponential decrease in the correlation coefficient between cavitation patterns in successive pulses from 0.5 ± 0.1 to 0.1 ± 0.1 as Δt increased from 2–200 ms; correspondingly, the lesion was completely fractionated with significantly fewer pulses for longer Δts. In the tissue study, given the same number of therapy pulses, complete and homogeneous tissue fractionation with well-defined lesion boundaries was achieved only for Δt ≥ 100 ms. These results indicated that the removal of the cavitation memory resulted in more efficient treatments and homogeneous lesions. PMID:22402025
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The association between sterilizing activity and drug distribution into tuberculosis lesions
Prideaux, Brendan; Via, Laura E.; Zimmerman, Matthew D.; Eum, Seokyong; Sarathy, Jansy; O’Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M.; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, TaeSun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N.; Barry, Clifton E.; Dartois, Véronique
2015-01-01
Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a MALDI mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration contributes to treatment outcome has wide implications for TB. PMID:26343800
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USDA-ARS?s Scientific Manuscript database
Lycopene is a red carotenoid found in tomatoes hypothesized to mediate disease preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, while human plasma and tissues demonstrate greater proportions of cis isomers. The objecti...
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NASA Astrophysics Data System (ADS)
Peña, Adrian F.; Devine, Jack; Doronin, Alexander; Meglinski, Igor
2014-03-01
We report the use of conventional Optical Coherence Tomography (OCT) for visualization of propagation of low frequency electric field in soft biological tissues ex vivo. To increase the overall quality of the experimental images an adaptive Wiener filtering technique has been employed. Fourier domain correlation has been subsequently applied to enhance spatial resolution of images of biological tissues influenced by low frequency electric field. Image processing has been performed on Graphics Processing Units (GPUs) utilizing Compute Unified Device Architecture (CUDA) framework in the frequencydomain. The results show that variation in voltage and frequency of the applied electric field relates exponentially to the magnitude of its influence on biological tissue. The magnitude of influence is about twice more for fresh tissue samples in comparison to non-fresh ones. The obtained results suggest that OCT can be used for observation and quantitative evaluation of the electro-kinetic changes in biological tissues under different physiological conditions, functional electrical stimulation, and potentially can be used non-invasively for food quality control.
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NASA Astrophysics Data System (ADS)
Koeppe, Robert Allen
Positron computed tomography (PCT) is a diagnostic imaging technique that provides both three dimensional imaging capability and quantitative measurements of local tissue radioactivity concentrations in vivo. This allows the development of non-invasive methods that employ the principles of tracer kinetics for determining physiological properties such as mass specific blood flow, tissue pH, and rates of substrate transport or utilization. A physiologically based, two-compartment tracer kinetic model was derived to mathematically describe the exchange of a radioindicator between blood and tissue. The model was adapted for use with dynamic sequences of data acquired with a positron tomograph. Rapid estimation techniques were implemented to produce functional images of the model parameters by analyzing each individual pixel sequence of the image data. A detailed analysis of the performance characteristics of three different parameter estimation schemes was performed. The analysis included examination of errors caused by statistical uncertainties in the measured data, errors in the timing of the data, and errors caused by violation of various assumptions of the tracer kinetic model. Two specific radioindicators were investigated. ('18)F -fluoromethane, an inert freely diffusible gas, was used for local quantitative determinations of both cerebral blood flow and tissue:blood partition coefficient. A method was developed that did not require direct sampling of arterial blood for the absolute scaling of flow values. The arterial input concentration time course was obtained by assuming that the alveolar or end-tidal expired breath radioactivity concentration is proportional to the arterial blood concentration. The scale of the input function was obtained from a series of venous blood concentration measurements. The method of absolute scaling using venous samples was validated in four studies, performed on normal volunteers, in which directly measured arterial concentrations were compared to those predicted from the expired air and venous blood samples. The glucose analog ('18)F-3-deoxy-3-fluoro-D -glucose (3-FDG) was used for quantitating the membrane transport rate of glucose. The measured data indicated that the phosphorylation rate of 3-FDG was low enough to allow accurate estimation of the transport rate using a two compartment model.
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Carneiro, Maria Fernanda Hornos; Oliveira Souza, Juliana Maria; Grotto, Denise; Batista, Bruno Lemos; de Oliveira Souza, Vanessa Cristina; Barbosa, Fernando
2014-10-01
Thimerosal (TM) is an ethylmercury (etHg)-containing preservative used in some vaccines despite very limited knowledge on the kinetics and direct interaction/effects in mammals׳ tissues after exposure. Thus, this study aimed to evaluate the kinetics of Hg species in mice in a time course analysis after intramuscular injection of TM, by estimating Hg half-lives in blood and tissues. Mice were exposed to one single intramuscular dose of 20 µg of Hg as TM. Blood, brain, heart, kidney and liver were collected at 0.5 hour (h), 1 h, 8 h, 16 h, 144 h, 720 h and 1980 h after TM exposure (n=4). Hg species in animal tissues were identified and quantified by speciation analysis via liquid chromatography hyphenated with inductively coupled mass spectrometry (LC-ICP-MS). It was found that the transport of etHg from muscle to tissues and its conversion to inorganic Hg (inoHg) occur rapidly. Moreover, the conversion extent is modulated in part by the partitioning between EtHg in plasma and in whole blood, since etHg is rapidly converted in red cells but not in a plasma compartment. Furthermore, the dealkylation mechanism in red cells appears to be mediated by the Fenton reaction (hydroxyl radical formation). Interestingly, after 0.5 h of TM exposure, the highest levels of both etHg and inoHg were found in kidneys (accounting for more than 70% of the total Hg in the animal body), whereas the brain contributed least to the Hg body burden (accounts for <1.0% of total body Hg). Thirty days after TM exposure, most Hg had been excreted while the liver presented the majority of the remaining Hg. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney. Taken together, our findings demonstrated that TM (etHg) kinetics more closely approximates Hg(2+) than methylmercury (meHg) while the kidney must be considered a potential target for etHg toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Josephson, Matthew P.; Sikkink, Laura A.; Penheiter, Alan R.
2011-12-16
Highlights: Black-Right-Pointing-Pointer Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. Black-Right-Pointing-Pointer Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. Black-Right-Pointing-Pointer It is a widely believed that MYL2 is a poor substrate for smMLCK. Black-Right-Pointing-Pointer In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. Black-Right-Pointing-Pointer Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca{sup 2+} sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chainmore » kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis-Menten V{sub max} and K{sub M} for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant kinase in cardiac tissue on the basis of its specificity, kinetics, and tissue expression.« less
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Bovine mammary stem cells: Cell biology meets production agriculture
USDA-ARS?s Scientific Manuscript database
Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...
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Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations.
Petrie Aronin, Caren E; Zhao, Yun M; Yoon, Justine S; Morgan, Nicole Y; Prüstel, Thorsten; Germain, Ronald N; Meier-Schellersheim, Martin
2017-11-21
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments. Published by Elsevier Inc.
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Moses, Sara K; Harley, John R; Lieske, Camilla L; Muir, Derek C G; Whiting, Alex V; O'Hara, Todd M
2015-11-15
Risk assessments of persistent organic pollutants (POPs) are often based on octanol-water (KOW) partitioning dynamics and may not adequately reflect bioaccumulation in air-breathing organisms. It has been suggested that compounds with low KOW and high octanol-air partitioning (KOA) coefficients have the potential to bioaccumulate in air-breathing organisms, including marine mammals. Here we evaluate differences in concentrations of POPs for two trophically matched Arctic species, spotted seal (Phoca largha) and sheefish (Stenodus leucichthys). We compared concentrations of 108 POPs in matched tissues (liver and muscle) across three ranges of KOW. We found a significant positive correlation between POP concentration and log KOA in spotted seal tissues for low log KOW compounds (log KOW <5.5, p<0.05). This provides further evidence for empirical models and observed bioaccumulation patterns in air-breathing organisms, and highlights the potential for bioaccumulation of these compounds in Arctic marine mammals. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Moses, Sara K.; Harley, John R.; Lieske, Camilla L.; Muir, Derek C.G.; Whiting, Alex V.; O'Hara, Todd M.
2015-01-01
Risk assessments of persistent organic pollutants (POPs) are often based on octanol-water (KOW) partitioning dynamics and may not adequately reflect bioaccumulation in air-breathing organisms. It has been suggested that compounds with low KOW and high octanol-air partitioning (KOA) coefficients have the potential to bioaccumulate in air-breathing organisms, including marine mammals. Here we evaluate differences in concentrations of POPs for two trophically matched Arctic species, spotted seal (Phoca largha) and sheefish (Stenodus leucichthys). We compared concentrations of 108 POPs in matched tissues (liver and muscle) across three ranges of KOW. We found a significant positive correlation between POP concentration and log KOA in spotted seal tissues for low log KOW compounds (log KOW <5.5, p<0.05). This provides further evidence for empirical models and observed bioaccumulation patterns in air-breathing organisms, and highlights the potential for bioaccumulation of these compounds in Arctic marine mammals. PMID:26440545
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Kogut, Michael H.; Swaggerty, Christina L.; Byrd, James Allen; Selvaraj, Ramesh; Arsenault, Ryan J.
2016-01-01
Non-typhoidal Salmonella enterica induces an early, short-lived pro-inflammatory response in chickens that is asymptomatic of clinical disease and results in a persistent colonization of the gastrointestinal (GI) tract that transmits infections to naïve hosts via fecal shedding of bacteria. The underlying mechanisms that control this persistent colonization of the ceca of chickens by Salmonella are only beginning to be elucidated. We hypothesize that alteration of host signaling pathways mediate the induction of a tolerance response. Using chicken-specific kinomic immune peptide arrays and quantitative RT-PCR of infected cecal tissue, we have previously evaluated the development of disease tolerance in chickens infected with Salmonella enterica serovar Enteritidis (S. Enteritidis) in a persistent infection model (4–14 days post infection). Here, we have further outlined the induction of an tolerance defense strategy in the cecum of chickens infected with S. Enteritidis beginning around four days post-primary infection. The response is characterized by alterations in the activation of T cell signaling mediated by the dephosphorylation of phospholipase c-γ1 (PLCG1) that inhibits NF-κB signaling and activates nuclear factor of activated T-cells (NFAT) signaling and blockage of interferon-γ (IFN-γ) production through the disruption of the JAK-STAT signaling pathway (dephosphorylation of JAK2, JAK3, and STAT4). Further, we measured a significant down-regulation reduction in IFN-γ mRNA expression. These studies, combined with our previous findings, describe global phenotypic changes in the avian cecum of Salmonella Enteritidis-infected chickens that decreases the host responsiveness resulting in the establishment of persistent colonization. The identified tissue protein kinases also represent potential targets for future antimicrobial compounds for decreasing Salmonella loads in the intestines of food animals before going to market. PMID:27472318
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Kogut, Michael H; Swaggerty, Christina L; Byrd, James Allen; Selvaraj, Ramesh; Arsenault, Ryan J
2016-07-27
Non-typhoidal Salmonella enterica induces an early, short-lived pro-inflammatory response in chickens that is asymptomatic of clinical disease and results in a persistent colonization of the gastrointestinal (GI) tract that transmits infections to naïve hosts via fecal shedding of bacteria. The underlying mechanisms that control this persistent colonization of the ceca of chickens by Salmonella are only beginning to be elucidated. We hypothesize that alteration of host signaling pathways mediate the induction of a tolerance response. Using chicken-specific kinomic immune peptide arrays and quantitative RT-PCR of infected cecal tissue, we have previously evaluated the development of disease tolerance in chickens infected with Salmonella enterica serovar Enteritidis (S. Enteritidis) in a persistent infection model (4-14 days post infection). Here, we have further outlined the induction of an tolerance defense strategy in the cecum of chickens infected with S. Enteritidis beginning around four days post-primary infection. The response is characterized by alterations in the activation of T cell signaling mediated by the dephosphorylation of phospholipase c-γ1 (PLCG1) that inhibits NF-κB signaling and activates nuclear factor of activated T-cells (NFAT) signaling and blockage of interferon-γ (IFN-γ) production through the disruption of the JAK-STAT signaling pathway (dephosphorylation of JAK2, JAK3, and STAT4). Further, we measured a significant down-regulation reduction in IFN-γ mRNA expression. These studies, combined with our previous findings, describe global phenotypic changes in the avian cecum of Salmonella Enteritidis-infected chickens that decreases the host responsiveness resulting in the establishment of persistent colonization. The identified tissue protein kinases also represent potential targets for future antimicrobial compounds for decreasing Salmonella loads in the intestines of food animals before going to market.
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NASA Astrophysics Data System (ADS)
Karahaliou, A.; Vassiou, K.; Skiadopoulos, S.; Kanavou, T.; Yiakoumelos, A.; Costaridou, L.
2009-07-01
The current study investigates whether texture features extracted from lesion kinetics feature maps can be used for breast cancer diagnosis. Fifty five women with 57 breast lesions (27 benign, 30 malignant) were subjected to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on 1.5T system. A linear-slope model was fitted pixel-wise to a representative lesion slice time series and fitted parameters were used to create three kinetic maps (wash out, time to peak enhancement and peak enhancement). 28 grey level co-occurrence matrices features were extracted from each lesion kinetic map. The ability of texture features per map in discriminating malignant from benign lesions was investigated using a Probabilistic Neural Network classifier. Additional classification was performed by combining classification outputs of most discriminating feature subsets from the three maps, via majority voting. The combined scheme outperformed classification based on individual maps achieving area under Receiver Operating Characteristics curve 0.960±0.029. Results suggest that heterogeneity of breast lesion kinetics, as quantified by texture analysis, may contribute to computer assisted tissue characterization in DCE-MRI.
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Positron kinetics in an idealized PET environment
Robson, R. E.; Brunger, M. J.; Buckman, S. J.; Garcia, G.; Petrović, Z. Lj.; White, R. D.
2015-01-01
The kinetic theory of non-relativistic positrons in an idealized positron emission tomography PET environment is developed by solving the Boltzmann equation, allowing for coherent and incoherent elastic, inelastic, ionizing and annihilating collisions through positronium formation. An analytic expression is obtained for the positronium formation rate, as a function of distance from a spherical source, in terms of the solutions of the general kinetic eigenvalue problem. Numerical estimates of the positron range - a fundamental limitation on the accuracy of PET, are given for positrons in a model of liquid water, a surrogate for human tissue. Comparisons are made with the ‘gas-phase’ assumption used in current models in which coherent scattering is suppressed. Our results show that this assumption leads to an error of the order of a factor of approximately 2, emphasizing the need to accurately account for the structure of the medium in PET simulations. PMID:26246002
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Seo, Seongho; Kim, Su Jin; Lee, Dong Soo; Lee, Jae Sung
2014-10-01
Tracer kinetic modeling in dynamic positron emission tomography (PET) has been widely used to investigate the characteristic distribution patterns or dysfunctions of neuroreceptors in brain diseases. Its practical goal has progressed from regional data quantification to parametric mapping that produces images of kinetic-model parameters by fully exploiting the spatiotemporal information in dynamic PET data. Graphical analysis (GA) is a major parametric mapping technique that is independent on any compartmental model configuration, robust to noise, and computationally efficient. In this paper, we provide an overview of recent advances in the parametric mapping of neuroreceptor binding based on GA methods. The associated basic concepts in tracer kinetic modeling are presented, including commonly-used compartment models and major parameters of interest. Technical details of GA approaches for reversible and irreversible radioligands are described, considering both plasma input and reference tissue input models. Their statistical properties are discussed in view of parametric imaging.
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Modeling texture kinetics during thermal processing of potato products.
Moyano, P C; Troncoso, E; Pedreschi, F
2007-03-01
A kinetic model based on 2 irreversible serial chemical reactions has been proposed to fit experimental data of texture changes during thermal processing of potato products. The model links dimensionless maximum force F*(MAX) with processing time. Experimental texture changes were obtained during frying of French fries and potato chips at different temperatures, while literature data for blanching/cooking of potato cubes have been considered. A satisfactory agreement between experimental and predicted values was observed, with root mean square values (RMSs) in the range of 4.7% to 16.4% for French fries and 16.7% to 29.3% for potato chips. In the case of blanching/cooking, the proposed model gave RMSs in the range of 1.2% to 17.6%, much better than the 6.2% to 44.0% obtained with the traditional 1st-order kinetics. The model is able to predict likewise the transition from softening to hardening of the tissue during frying.
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NASA Astrophysics Data System (ADS)
Waldbusser, George G.; Brunner, Elizabeth L.; Haley, Brian A.; Hales, Burke; Langdon, Christopher J.; Prahl, Frederick G.
2013-05-01
Acidified waters are impacting commercial oyster production in the U.S. Pacific Northwest, and favorable carbonate chemistry conditions are predicted to become less frequent. Within 48 h of fertilization, unshelled Pacific oyster (Crassostrea gigas) larvae precipitate roughly 90% of their body weight as calcium carbonate. We measured stable carbon isotopes in larval shell and tissue and in algal food and seawater dissolved inorganic carbon in a longitudinal study of larval development and growth. Using these data and measured biochemical composition of larvae, we show that sensitivity of initial shell formation to ocean acidification results from diminished ability to isolate calcifying fluid from surrounding seawater, a limited energy budget and a strong kinetic demand for calcium carbonate precipitation. Our results highlight an important link between organism physiology and mineral kinetics in larval bivalves and suggest the consideration of mineral kinetics may improve understanding winners and losers in a high CO2 world.
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Light-induced biophotonic emission from plant tissues.
Bajpai, R P; Bajpai, P K
1992-07-01
The emission of biophotons in the visible range, following a delay time of 2-200 seconds after exposure to light, has been measured in germinating seeds, roots, flowers, leaves, and cells. It was found that the biophotonic signals are reproducible and light-induced. The observed signals from germinating seeds of Phaseolus aures and decaying leaves of Eucalyptus are presented to show that the signals have characteristic kinetics and intensity. The kinetics of the signal was found to be independent of the stage of growth or decay, though its intensity varied with biological factors. The kinetics in the first minute is characterized by a single exponential decay term while that in the region t less than or equal to 200 s is characterized by two exponentials. The variation in the intensity of the signal with mass, state of hydration, and growth, and the effect of inhibitors in various systems (e.g. leaves, lichen, Chlorella) are reported.
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Merok, Joshua R; Lansita, Janice A; Tunstead, James R; Sherley, James L
2002-12-01
A long-standing intriguing hypothesis in cancer biology is that adult stem cells avoid mutations from DNA replication errors by a unique pattern of chromosome segregation. At each asymmetric cell division, adult stem cells have been postulated to selectively retain a set of chromosomes that contain old template DNA strands (i.e., "immortal DNA strands"). Using cultured cells that cycle with asymmetric cell kinetics, we confirmed both the existence of immortal DNA strands and the cosegregation of chromosomes that bear them. Our findings also lead us to propose a role for immortal DNA strands in tissue aging as well as cancer.