Miracle-dz/UniFAR-FTUs huggingface dataset:
Melatonin inhibits the contractile effect of vanadate in the isolated pulmonary arterial rings of rats: Possible role of hydrogen peroxide

The effect and possible mechanism of action of vanadate on the isolated pulmonary arterial rings of normal rats were studied. Pulmonary arterial rings contracted in response to vanadate (0.1–1 mM) in a concentration‐dependent manner. Preincubation of the pulmonary arterial rings with 1 mM melatonin significantly reduced the contractile effect of vanadate by more than 60%. Furthermore, addition of hydrogen peroxide (50 μM) or enzymatic generation of hydrogen peroxide by the addition of glucose oxidase (10 U/mL) to the medium containing glucose produced remarkable increases in the pulmonary arterial tension, 46.2 ± 7.3 and 78.7 ± 9.7 g tension/g tissue, respectively. Similarly, incubation of the pulmonary arterial rings with 1 mM melatonin significantly reduced the contractile responses of the arterial rings to hydrogen peroxide and glucose/glucose oxidase to 25.7 ± 2.9 and 24.7 ± 4.4 g tension/g tissue, respectively. Vanadate, in vitro, significantly stimulated the oxidation of NADH by xanthine oxidase, and the rate of oxidation was increased by increasing either time or vanadate concentration. Similarly, addition of melatonin to a reaction mixture containing xanthine oxidase and vanadate significantly inhibited the rate of NADH oxidation in a concentration‐dependent fashion. The results of the present study indicated that vanadate induced contraction in the isolated pulmonary arterial rings, which was significantly reduced by melatonin. Furthermore, the contractile effect of vanadate on the pulmonary arterial rings may be attributed to the intracellular generation of hydrogen peroxide. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:273–278, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10049
Human relevance framework for rodent liver tumors induced by the insecticide sulfoxaflor

Abstract Sulfoxaflor, a novel active substance that targets sap-feeding insects, induced rodent hepatotoxicity when administered at high dietary doses. Specifically, hepatocellular adenomas and carcinomas increased after 18 months in male and female CD-1 mice at 750 and 1250 ppm, respectively, and hepatocellular adenomas increased after 2 years in male F344 rats at 500 ppm. Studies to determine the mode of action (MoA) for these liver tumors were performed in an integrated and prospective manner as part of the standard battery of toxicology studies such that the MoA data were available prior to, or by the time of, the completion of the carcinogenicity studies. Sulfoxaflor is not genotoxic and the MoA data support the following key events in the etiology of the rodent liver tumors: (1) CAR nuclear receptor activation and (2) hepatocellular proliferation. The MoA data were evaluated in a weight of evidence approach using the Bradford Hill criteria for causation and were found to align with dose and temporal concordance, biological plausibility, coherence, strength, consistency, and specificity for a CAR-mediated MoA while excluding other alternate MoAs. The available data include: activation of CAR, Cyp2b induction, hepatocellular hypertrophy and hyperplasia, absence of liver effects in KO mice, absence of proliferation in humanized mice, and exclusion of other possible mechanisms (e.g., genotoxicity, cytotoxicity, AhR, or PPAR activation), and indicate that the identified rodent liver tumor MoA for sulfoxaflor would not occur in humans. In this case, sulfoxaflor is considered not to be a potential human liver carcinogen.
Osteoarthritis and the Tactical Athlete: A Systematic Review.

OBJECTIVE Although tactical athletes (eg, military service members, law enforcement personnel, fire fighters) are exposed to several known risk factors, it remains unclear if they are at increased risk for osteoarthritis (OA). The purpose of this systematic review was to investigate the association between serving as a tactical athlete and the incidence and prevalence of OA. DATA SOURCES We completed a comprehensive systematic literature search in November 2014 using 12 bibliographic databases (eg, PubMed, Ovid, SportDiscus) supplemented with manual searches of reference lists. STUDY SELECTION Studies were included if they met the following criteria: (1) an aim of the study was to investigate an association between tactical athletes and OA; (2) the outcome measure was radiographic OA, clinical OA, total joint replacement, self-reported diagnosis of OA, or placement on a waiting list for a total joint replacement; (3) the study design was a cohort study; and (4) the study was written in English. DATA EXTRACTION One investigator extracted data from articles that met all inclusion criteria (eg, group descriptions, measures of disease burden, source of nonexposed controls). DATA SYNTHESIS Twelve articles met the inclusion criteria and described retrospective cohort studies. Firefighters, active-duty military service members, and veteran military parachutists consistently had a higher incidence or prevalence of knee, hip, or any OA diagnosis (4 studies). Active-duty pilots and veteran military parachutists may have a higher prevalence of spine OA, but this was not statistically significant (2 studies). Occupational risk factors for OA among tactical athletes include rank and branch of military service. The risk of OA among individuals who completed mandatory national military service remains unclear (6 studies). CONCLUSIONS The incidence of OA among tactical athletes appears to be significantly higher when compared with nonexposed controls. Further research is needed to specifically identify modifiable risk factors within this high-risk population to develop and implement effective risk-reduction strategies.
White matter hyperintensities and gray matter lesions in physically healthy depressed subjects.

OBJECTIVE Previous studies reported that depressed subjects had more white matter hyperintensities on magnetic resonance imaging scans than control subjects, but the subjects had cerebrovascular disease risk factors. This study used subjects with a history of recurrent major depression and matched comparison subjects, screened to exclude cerebrovascular disease risk factors, to determine whether depressed subjects had more white matter hyperintensities and other lesions. METHOD A semiautomated volumetric computer program was used to compare numbers and volumes of white matter hyperintensities, basal ganglia lesions, and total lesions in 24 women with a history of recurrent major depression and 24 comparison subjects case-matched on age and education and group-matched on height. In addition, images were measured with the use of a validated categorical scale. All subjects were screened to exclude cerebrovascular disease risk factors. RESULTS There were no significant differences in the total volumes or total numbers of lesions. However, multiple linear regression showed a significant correlation of age and depression with number of lesions; this was accounted for by a greater number of small lesions (diameter < or = 0.4 cm). CONCLUSIONS These findings suggest that cerebrovascular disease risk factors most likely mediated the relationship between depression and white matter hyperintensities seen in previous studies. However, the independent effect of depression, as well as an age-by-depression interaction, for small lesions suggests a causal role of depression in certain types of white matter pathology irrespective of other cerebrovascular disease risk factors. The volumetric method used in this study may be more sensitive than other methods in determining lesion characteristics and correlations with clinical variables.
Optimal Taxation with Heterogeneous Skills and Elasticities: Structural and Sufficient Statistics Approaches

The usual approach to calibrate optimal tax formulae consists in using the observed sufficient statistics, which is only correct as long as they correspond to the optimal sufficient statistics. In the very general case where agents are heterogeneous in many dimensions, we propose a new structural method (based on an allocation perturbation) from which we derive the optimal income tax formula and its optimal sufficient statistics computed from the observed ones. This allows us to quantify the error in the marginal tax rates entailed by using observed rather than optimal sufficient statistics. On US data, we show that this error can be considerable (up to 10 percentage points). We also call for a change of focus in the empirical analysis of top tax rates. Since individuals are heterogeneous along multiple dimensions, one needs to estimate the elasticity of those whose income density has the fatter tail.
An analysis of demand for money in Uganda (1986 - 2003)

(ix) LIST OF ABBREVIATIONS. (x) CHAPTER ONE. 1 1.0 INTRODUCTION. 1 1.1 Monetary Policy and Review of the Ugandan Economy.1 1.2 Statement of the problem. 5 1.3 Objectives of the Study. 6 1.4 Significance of the Study. 6 1.6 Scope of the Study.7 1.4 Organization of the Study. 7 CHAPTER TWO. 8 2.0 LITERATURE REVIEW. 8 2.1 Theories of Money demand. 8 2.1.1 Classical Theories. 8 2.1.2 Keynesian Theory. 8 2.1.3 Post Keynes Theory.9 2.1.3 Friedman's Modem Theory of Money. 10 2.2 Empirical Literature Review . 11 2.3 Overview of the literature. 23 CHAPTER THREE. 24 3.0 METHODOLOGY.24 3.1 Selection of Variables. 24 3.1.1 Money S tock.24 3.1.2 Scale variable.25 3.1.3 Financial innovation . 25 3.1.4 Opportunity cost variable. 25 3.2 Model Specification.27
Survival of Anesthetized Sus scrofa After Cycling (7-Second On/3-Second Off) Exposures to an Electronic Control Device for 3 Minutes

Electronic control devices (ECDs) may eventually be deployed by the military in a manner resulting in longer exposures than those encountered during law-enforcement operations. In a previous study, 18 repeated cycling (5-second on/5-second off) exposures (within a 3-minute period) of anesthetized swine to an ECD (TASER International's Advanced TASER X26 device) resulted in leg muscle contraction, acidosis, and increases in blood electrolytes. In the current study, experiments were performed to examine effects of exposures to a different cycling rate (7-second on/3-second off), from a modified X26 ECD, on 10 swine (Sus scrofa), maintained on propofol anesthesia. In contrast with the previous study, a large number of animals (6/10) died immediately after the exposures. There were no major differences in pre-exposure blood factors from survivors versus nonsurvivors, with the exception of hematocrit and 2 isoenzymes of lactate dehydrogenase. It is doubtful that these factors would be useful in predicting survival after ECD exposure. Blood pH was significantly decreased after exposure, but (in animals that survived) subsequently returned to baseline levels. On the basis of the overall survival rate, further development of useful ECDs (for long-term incapacitation during military operations) may require consideration of longer pauses between repeated exposures over a 3-minute period.
Large Scale Phosphoproteome Profiles Comprehensive Features of Mouse Embryonic Stem Cells*

Embryonic stem cells are pluripotent and capable of unlimited self-renewal. Elucidation of the underlying molecular mechanism may contribute to the advancement of cell-based regenerative medicine. In the present work, we performed a large scale analysis of the phosphoproteome in mouse embryonic stem (mES) cells. Using multiplex strategies, we detected 4581 proteins and 3970 high confidence distinct phosphosites in 1642 phosphoproteins. Notably, 22 prominent phosphorylated stem cell marker proteins with 39 novel phosphosites were identified for the first time by mass spectrometry, including phosphorylation sites in NANOG (Ser-65) and RE1 silencing transcription factor (Ser-950 and Thr-953). Quantitative profiles of NANOG peptides obtained during the differentiation of mES cells revealed that the abundance of phosphopeptides and non-phosphopeptides decreased with different trends. To our knowledge, this study presents the largest global characterization of phosphorylation in mES cells. Compared with a study of ultimately differentiated tissue cells, a bioinformatics analysis of the phosphorylation data set revealed a consistent phosphorylation motif in human and mouse ES cells. Moreover, investigations into phosphorylation conservation suggested that phosphoproteins were more conserved in the undifferentiated ES cell state than in the ultimately differentiated tissue cell state. However, the opposite conclusion was drawn from this conservation comparison with phosphosites. Overall, this work provides an overview of phosphorylation in mES cells and is a valuable resource for the future understanding of basic biology in mES cells.
Development of a new Leydig cell population after the destruction of existing Leydig cells by ethane dimethane sulphonate in rats: an autoradiographic study.

The formation of new Leydig cells in adult male rats was studied after the complete destruction of the original population by ethane dimethane sulphonate (EDS). Following administration of EDS, proliferating interstitial cells were labelled in a pulse-chase experiment by way of three [3H]thymidine injections on days 2, 3 and 4 after EDS administration. Some of the newly formed Leydig cells found 14 days after EDS administration were labelled with [3H]thymidine, indicating that these Leydig cells were derived from precursor cells, most likely mesenchymal cells, that had incorporated [3H]thymidine at days 2, 3 or 4 after EDS administration. At 21 days after EDS administration, the total number of Leydig cells (labelled plus unlabelled) had increased 7- to 16-fold compared with the number of cells that were present 14 days after EDS had been administered. In a second series of experiments, [3H]thymidine was given 2 h before the rats were killed (short-term labelling experiment). In this experiment it was shown that the proliferative activity of the mesenchymal cells, which are presumed to be the precursors of the Leydig cells, after a considerable increase at day 2 after EDS administration, had returned to the control level at day 7. However, the total number of mesenchymal cells (labelled plus unlabelled) remained increased from 2 to 49 days after EDS administration. This indicated that the majority of the new Leydig cells which were formed from day 14 onwards probably did not derive from differentiating mesenchymal cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid function in treatment-resistant schizophrenia patients treated with quetiapine, risperidone, or fluphenazine.

BACKGROUND Thyroid dysfunction is relatively common in patients with schizophrenia, possibly related to a genetic linkage of the disorders and to antipsychotic treatment. Quetiapine has been implicated as causing some degree of thyroid function changes, yet it remains unclear as to what extent or why these changes may occur. Furthermore, the need for thyroid function monitoring in patients taking this medication is not definitive. METHOD Thyroid function was assessed in 38 adult DSM-IV-diagnosed schizophrenia patients after 6 weeks of prospective, double-blind, randomized treatment with quetiapine (400 mg/day), risperidone (4 mg/day), or fluphenazine (12.5 mg/day). Data were collected from 1997 to 2002. RESULTS At baseline, the percentages of randomized patients with abnormal values were 18% (4/22) for serum T(3) resin uptake, 13% (4/30) for thyroid-stimulating hormone (TSH), and 9% (2/22) for total serum thyroxine (TT(4)), representing fairly widespread thyroid abnormalities independent of treatment group. Little change was noted in thyroid function during the 6 weeks of treatment, except for a significant decrease in TT(4) values for those taking quetiapine (p = .01). Clinically, however, no patients demonstrated any signs or symptoms of hypothyroidism during the study, nor were any significant changes in the free thyroxine index or TSH levels noted. CONCLUSIONS It is expected that TT(4) levels will decrease during quetiapine treatment, and this may possibly be related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase. Routine monitoring of thyroid function in quetiapine-treated patients without a history of thyroid disease is not recommended.
Pharmacological Targeting of Anaphylatoxin Receptors during the Effector Phase of Allergic Asthma Suppresses Airway Hyperresponsiveness and Airway Inflammation1

Airway hyperresponsiveness and airway inflammation are hallmarks of allergic asthma, the etiology of which is crucially linked to the presence of Th2 cytokines. A role for the complement anaphylatoxins C3a and C5a in allergic asthma was suggested, as deficiencies of the C3a receptor (C3aR) and of complement factor C5 modulate airway hyperresponsiveness, airway inflammation, and Th2 cytokine levels. However, such models do not allow differentiation of effects on the sensitization phase and the effector phase of the allergic response, respectively. In this study, we determined the role of the anaphylatoxins on the effector phase of asthma by pharmacological targeting of the anaphylatoxin receptors. C3aR and C5a receptor (C5aR) signaling was blocked using the nonpeptidic C3aR antagonist SB290157 and the neutralizing C5aR mAb 20/70 in a murine model of Aspergillus fumigatus extract induced pulmonary allergy. Airway hyperresponsiveness was substantially improved after C5aR blockade but not after C3aR blockade. Airway inflammation was significantly reduced in mice treated with the C3aR antagonist or the anti-C5aR mAb, as demonstrated by reduced numbers of neutrophils and eosinophils in bronchoalveolar lavage fluid. Of note, C5aR but not C3aR inhibition reduced lymphocyte numbers in bronchoalveolar lavage fluid. Cytokine levels of IL-5 and IL-13 in bronchoalveolar lavage fluid were not altered by C3aR or C5aR blockade. However, blockade of both anaphylatoxin receptors markedly reduced IL-4 levels. These data suggest an important and exclusive role for C5aR signaling on the development of airway hyperresponsiveness during pulmonary allergen challenge, whereas both anaphylatoxins contribute to airway inflammation and IL-4 production.
Bilateral progressive essential iris atrophy and keratoconus with coincident features of posterior polymorphous dystrophy: a case report and proposed pathogenesis.

We report the first case known to us of an apparent bilateral association of essential iris atrophy (EIA) and keratoconus (KC), with coincident features of posterior polymorphous dystrophy (PPD). Based on this case and the published natural history and findings of both the irido corneal endothelial (ICE) syndrome and PPD, we propose a new hypothesis for the pathogenesis of the ICE syndrome with associated KC and/or PPD. We suggest that, similar to the genetics of retinoblastoma, the predisposition for either the ICE syndrome or for PPD is inherited as an inactive allele, the so-called "first hit. " Inactivation of the second allele, or "second hit," which could occur at any time, might be the product of the background mutation rate or of an environmental trigger. Dedifferentiation or an abnormality in normal development could occur after the first or second hit, resulting in varying clinical patterns. We also concur with other investigators that PPD could be part of the spectrum of the ICE syndrome, owing to similarities in their clinical presentations, histopathology, specular and electron microscopy, and natural history.
CD4+CD25+ Regulatory T Cells in Transplantation: Progress, Challenges and Prospects

The involvement of CD4+CD25+ regulatory T cells (Treg) in general immune homeostasis and protection from autoimmune syndromes is now well established. Similarly, there has been increasing evidence for Treg involvement in allograft rejection and current immunotherapies. However, despite significant advances in understanding the development, function, and therapeutic efficacy of Treg in certain well‐defined rodent models, the relevance of Treg to clinical transplantation remains unclear. In this review, we summarize our current understanding of the role of Treg in immunity and organ transplantation in experimental and clinical settings. In addition, we review advances in using Treg as a form of immune therapy. The goal is to highlight the complexities and opportunities in the field and to provide evidence to support the use of antigen‐specific Tregs in the context of transplantation to facilitate a robust and selective state of immune tolerance.
Expression of Mouse Mammary Tumor Virus Superantigen mRNA in the Thymus Correlates with Kinetics of Self-Reactive T-Cell Loss

ABSTRACT Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is expressed at the surface of antigen-presenting cells in conjunction with major histocompatibility complex (MHC) type II molecules. The Sag-MHC complex is recognized by entire subsets of T cells, leading to cytokine release and amplification of infected B and T cells that carry milk-borne MMTV to the mammary gland. Expression of Sag proteins from endogenous MMTV proviruses carried in the mouse germ line usually results in the deletion of self-reactive T cells during negative selection in the thymus and the elimination of T cells required for infection by specific milk-borne MMTVs. However, other endogenous MMTVs are unable to eliminate Sag-reactive T cells in newborn mice and cause partial loss of reactive T cells in adults. To investigate the kinetics of Sag-reactive T-cell deletion, backcross mice that contain single or multiple MMTVs were screened by a novel PCR assay designed to distinguish among highly related MMTV strains. Mice that containedMtv-17 alone showed slow kinetics of reactive T-cell loss that involved the CD4+, but not the CD8+, subset. Deletion of CD4+ or CD8+ T cells reactive with Mtv-17 Sag was not detected in thymocytes. Slow kinetics of peripheral T-cell deletion by Mtv-17 Sag also was accompanied by failure to detect Mtv-17 sag-specific mRNA in the thymus, despite detectable expression in other tissues, such as spleen. Together, these data suggest thatMtv-17 Sag causes peripheral, rather than intrathymic, deletion of T cells. Interestingly, the Mtv-8 provirus caused partial deletion of CD4+Vβ12+ cells in the thymus, but other T-cell subsets appeared to be deleted only in the periphery. Our data have important implications for the level of antigen expression required for elimination of self-reactive T cells. Moreover, these experiments suggest that mice expressing endogenous MMTVs that lead to slow kinetics of T-cell deletion will be susceptible to infection by milk-borne MMTVs with the same Sag specificity.