The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the ...National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.
Abstract Heart transplantation is an established treatment for end-stage cardiac disease. This study describes parenthood after heart transplantation in the New Zealand population. An analysis was ...performed of all heart recipients from the New Zealand program. Exclusion criteria were death within 3 months of transplantation or age <18 years at the time of the survey. Recipients (or next of kin if recipients deceased) were surveyed regarding family status at the time of transplantation and new parenthood after transplantation. A total of 145 of 199 eligible recipients completed the survey ∼12.2 years after transplant (119 male, 26 female). Before transplantation, 81% were in a permanent relationship; 72% had children. After transplantation, 19/45 recipients had 27 children (2 female recipients had 3 children), of whom 15 were planned. Complications occurred in 7/27 pregnancies (including one atrial septal defect requiring surgery). Two recipients died after the birth of their children (children aged 2.6 and 14.1 years). This study provides unique data relevant to both female and male recipients regarding new parenthood after heart transplantation and will promote more informed discussion with transplant recipients.
To evaluate the potential effects of seed orchard pollen contamination from surrounding background sources, we made control pollinations with outside orchard pollen and inside orchard pollen on trees ...of a Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) coastal-interior transition zone seed orchard. The resulting progeny were tested on a transition zone and a coastal site. After nine growing seasons, survival was above 90% on both sites for both pollen sources, and the trees height differences due to pollen source were statistically nonsignificant. Wildstand operational seedlots, used as controls, were 17% shorter than the "contaminated" seedlings. Orchard management implications of these results are discussed.
Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative ...regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal -2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-beta1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-beta1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal -2.9 kb promoter.
Acid suppression therapy (AST) is routinely used in critically ill patients to prevent stress-related mucosal bleeding (SRMB).
Our objective was to determine the impact of a structured educational ...intervention on AST used for prevention of SRMB on appropriateness of AST.
A single-center, retrospective, cohort study of appropriate use of AST in critically ill patients admitted to the medical intensive care unit (ICU) at an academic medical center between January to June of 2014 (no intervention) and January to June of 2015 (intervention) was conducted. The percentage of patients prescribed inappropriate AST, inappropriate AST at ICU transfer and hospital discharge, doses of inappropriate AST, and adverse effects associated with AST use were compared between periods using chi-square tests.
Patients in the intervention group (n=118) were 5 years older than patients in the no intervention group (n=101). AST was inappropriately initiated more frequently in the no intervention group (23% vs. 11%, p=0.012). Continuation of inappropriate AST at ICU transfer and hospital discharge was similar between groups (60% vs. 53%, p=0.277 and 18% vs. 14%, p=0.368, respectively).
Patients had appropriate AST initiated and inappropriate AST withheld more frequently when formal education was provided. This low-cost intervention strategy can be implemented easily at institutions where pharmacists interact with physicians on rounding services and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.
Abstract Objective Electroencephalograph recorded in the first day of life in newborns treated with hypothermia for hypoxic-ischemic encephalopathy could be utilized as a predictive tool for the ...severity of brain injury on magnetic resonance imaging and mortality. Study design This work was a retrospective study of newborns who were admitted for therapeutic hypothermia due to hypoxic-ischemic encephalopathy. All enrolled infants underwent encephalography within the first 24 hours of life and underwent brain magnetic resonance imaging after rewarming. All encephalographs were independently reviewed for background amplitude, continuity, and variability. Brain injury determined by magnetic resonance imaging was scored using methods described by Bonifacio et al. Results Forty-one newborns were included in the study. Each encephalograph variable correlated significantly with the severity of injury on brain magnetic resonance imaging ( P < 0.001 for each). The overall encephalograph severity estimated as mild, moderate, and severe also correlated with injury ( P < 0.001). Each encephalograph variable correlated with mortality ( P < 0.001 for each) and also the overall encephalograph severity ( P < 0.001). Conclusion Severity of electrographic findings on encephalograph in the first day of life during therapeutic hypothermia for hypoxic-ischemic encephalopathy correlated with the extent of injury on brain magnetic resonance imaging. This information may be useful for families and aid guide clinical decision making.
Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis and has been reported to be an independent risk factor for ischemic cardiovascular events. This study describes the age-dependent ...development of spontaneous coronary arterial thrombi that are associated with evidence of subendocardial myocardial infarction in mice transgenic for human PAI-1.
We generated two independent transgenic mice founder lines that express a stable variant of active human PAI-1 under control of the murine preproendothelin-1 (mPPET-1) promoter. Backcrossed homozygous transgenic animals from founder line I had plasma PAI-1 levels of 23+/-12 ng/mL. PAI-1 transgenic animals younger than 4 months do not exhibit any evidence of arterial or venous thrombosis. Ninety percent of transgenic animals (n=10) older than 6 months developed spontaneous occlusions of typically multiple, penetrating coronary arteries, with histological evidence of subendocardial infarction identified in 50% of animals.
This study shows that chronically elevated levels of PAI-1 are associated with age-dependent coronary arterial thrombosis in mice transgenic for human PAI-1. This is the first study of a murine model of coronary thrombosis that occurs in the absence of severe hypercholesterolemia or multiple genetic manipulations. These findings provide new evidence to support the hypothesis that PAI-1 excess contributes to the development of coronary arterial thrombosis.
We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, ...phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.
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