Sacrificial utilitarian judgments do reflect concern for the greater good: Clarification via process dissociation and the judgments of philosophers.

Researchers have used "sacrificial" trolley-type dilemmas (where harmful actions promote the greater good) to model competing influences on moral judgment: affective reactions to causing harm that motivate characteristically deontological judgments ("the ends don't justify the means") and deliberate cost-benefit reasoning that motivates characteristically utilitarian judgments ("better to save more lives"). Recently, Kahane, Everett, Earp, Farias, and Savulescu (2015) argued that sacrificial judgments reflect antisociality rather than "genuine utilitarianism," but this work employs a different definition of "utilitarian judgment." We introduce a five-level taxonomy of "utilitarian judgment" and clarify our longstanding usage, according to which judgments are "utilitarian" simply because they favor the greater good, regardless of judges' motivations or philosophical commitments.

Radial growth of Pinus sylvestris growing on alluvial terraces is sensitive to water-level fluctuations.

Along the Alpine river Lech (Tyrol, Austria), poorly grown Scots pine (Pinus sylvestris) stands dominate on dry alluvial terraces, which are made up of coarse calcareous gravel. Here we evaluated the impact of environmental factors, such as precipitation, temperature and water table, on annual variability of radial growth. Tree-ring chronologies from six stands comprising different age classes were developed by extracting two core samples from more than 15 trees per plot.

Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta.

In the arterial circulation, regions of disturbed flow (DF), which are characterized by flow separation and transient vortices, are susceptible to atherogenesis, whereas regions of undisturbed laminar flow (UF) appear protected. Coordinated regulation of gene expression by endothelial cells (EC) may result in differing regional phenotypes that either favor or inhibit atherogenesis. Linearly amplified RNA from freshly isolated EC of DF (inner aortic arch) and UF (descending thoracic aorta) regions of normal adult pigs was used to profile differential gene expression reflecting the steady state in vivo.

Fidelity and enhanced sensitivity of differential transcription profiles following linear amplification of nanogram amounts of endothelial mRNA.

Although mRNA amplification is necessary for microarray analyses from limited amounts of cells and tissues, the accuracy of transcription profiles following amplification has not been well characterized. We tested the fidelity of differential gene expression following linear amplification by T7-mediated transcription in a well-established in vitro model of cytokine [tumor necrosis factor alpha (TNFalpha)]-stimulated human endothelial cells using filter arrays of 13,824 human cDNAs. Transcriptional profiles generated from amplified antisense RNA (aRNA) (from 100 ng total RNA, approximately 1 ng mRNA) were compared with profiles generated from unamplified RNA originating from the same homogeneous pool.

The convergence of haemodynamics, genomics, and endothelial structure in studies of the focal origin of atherosclerosis.

The completion of the Human Genome Project and ongoing sequencing of mouse, rat and other genomes has led to an explosion of genetics-related technologies that are finding their way into all areas of biological research; the field of biorheology is no exception. Here we outline how two disparate modern molecular techniques, microarray analyses of gene expression and real-time spatial imaging of living cell structures, are being utilized in studies of endothelial mechanotransduction associated with controlled shear stress in vitro and haemodynamics in vivo. We emphasize the value of such techniques as components of an integrated understanding of vascular rheology.

Hemodynamics and the focal origin of atherosclerosis: a spatial approach to endothelial structure, gene expression, and function.

Atherosclerosis originates at predictable focal and regional sites that are associated with complex flow disturbances and flow separations in large arteries. The spatial relationships associated with hemodynamic shear stress forces acting on the endothelial monolayer are considered in experiments that model regions susceptible to atherosclerosis (flow disturbance) and resistant to atherosclerosis (undisturbed flow). Flow disturbance in vitro induced differential expression at the single gene level as illustrated for the intercellular communication gene and protein, connexin 43.

A spatial approach to transcriptional profiling: mechanotransduction and the focal origin of atherosclerosis.

The initiation and progression of focal atherosclerotic lesions has long been known to be associated with regions of disturbed blood flow. Improved precision in experimental models of spatially defined flow has recently been combined with regional and single-cell gene-expression profiling to investigate the relationships linking haemodynamics to vessel-wall pathobiology.

Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro.

Hemodynamic regulation of the endothelial gap junction protein connexin43 (Cx43) was studied in a model of controlled disturbed flows in vitro. Cx43 mRNA, protein expression, and intercellular communication were mapped to spatial variations in fluid forces. Hemodynamic features of atherosclerotic lesion-prone regions of the vasculature (flow separation and recirculation) were created for periods of 5, 16, and 30 h, with laminar shear stresses ranging between 0 and 13.

Connexin43 gene expression in the rabbit arterial wall: effects of hypercholesterolemia, balloon injury and their combination.

The specialized functions of endothelium require intercellular communication between endothelial cells within the monolayer, and between endothelium and other cells present in the vessel wall. This is accomplished by a combination of paracrine soluble mediators and direct gap-junctional intercellular communication (GJIC) mediated by a family of connexin proteins. A prominent connexin expressed by vascular cells in vivo and in vitro is connexin 43 (Cx43).

Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction.

Blood flow interactions with the vascular endothelium represent a specialized example of mechanical regulation of cell function that has important physiological and pathological cardiovascular consequences. The endothelial monolayer in vivo acts as a signal transduction interface for forces associated with flowing blood (hemodynamic forces) in the acute regulation of artery tone and chronic structural remodeling of arteries, including the pathology of atherosclerosis. Mechanisms related to spatial relationships at the cell surfaces and throughout the cell that influence flow-mediated endothelial mechanotransduction are discussed.

Effects of wall shear stress and fluid recirculation on the localization of circulating monocytes in a three-dimensional flow model.

There is a correlation between the location of early atherosclerotic lesions and the hemodynamic characteristics at those sites. Circulating monocytes are key cells in the pathogenesis of atherosclerotic plaques and localize at sites of atherogenesis. The hypothesis that the distribution of monocyte adhesion to the vascular wall is determined in part by hemodynamic factors was addressed by studying monocyte adhesion in an in vitro flow model in the absence of any biological activity in the model wall.

Changes in gap junction connexin-43 messenger ribonucleic acid levels associated with rat ovarian follicular development as demonstrated by in situ hybridization.

Objective: The purpose was to evaluate the changes in gap junction connexin-43 messenger ribonucleic acid levels associated with rat ovarian follicular development. Gap junctions connect the plasma membranes of adjacent cells through cell-to-cell channels, allowing synchronization of cellular events, including ovarian follicular development. Ovarian gap junctions consist of the protein connexin-43.

Gap junctional communication between vascular cells. Induction of connexin43 messenger RNA in macrophage foam cells of atherosclerotic lesions.

The structure and function of blood vessels depend on the ability of vascular cells to receive and transduce signals and to communicate with each other. One means by which vascular cells have been shown to communicate is via gap junctions, specifically connexin43. In atherosclerosis, the normal physical patterns of communication are disrupted by the subendothelial infiltration and accumulation of blood monocytes, which in turn can differentiate into resident foam cells.

Hemodynamic forces and vascular cell communication in arteries.

As the interface between the blood and the rest of the vessel wall, the endothelium is directly affected by hemodynamic shear stress (frictional) forces that locally regulate vascular tone and are implicated in the localization of atherosclerosis. There are many diverse responses of endothelial cells to hemodynamically related mechanical stresses ranging from ion channel activation to gene regulatory events. The processes of force transmission from the blood to the cell, and force transduction within the endothelium to electrophysiologic, biochemical, and transcriptional responses are poorly understood.

Comparative binding and degradation of lipoprotein(a) and low density lipoprotein by human monocyte-derived macrophages.

The binding and degradation of equimolar concentrations of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) isolated from the same individual were studied in primary cultures of human monocyte-derived macrophages (HMDM). At 4 degrees C, LDL receptor-mediated binding of both Lp(a) and LDL was of low affinity, being 0.8 and 0.

Rat ovarian apolipoprotein E: localization and gonadotropic control of messenger RNA.

Apolipoprotein E (apo E) is a 35-kDa protein found in association with various lipoproteins. It is synthesized by a wide variety of tissues, including the ovary. It can serve several functions, such as 1) transport of excess cholesterol from peripheral tissue to the liver; 2) directed movement of cholesterol from areas of high to low cholesterol concentration within tissue or organs; and 3) inhibition of the conversion of theca progesterone to androgen, thus acting as an autocrine or paracrine factor within the ovary.

Human ovarian granulosa cell culture: determination of blood cell contamination and evaluation of possible culture purification steps.

Objective: To determine the degree of blood cell contamination in GC preparations; to assess techniques of GC purification; and to determine possible effects of contaminating cells and purification techniques on cultured GC in terms of steroid hormone production.

Design: Contamination of GC by white blood cells was assessed by Wright's stain and immunohistochemistry. Purification was attempted by: (1) Ficoll density centrifugation (to remove polymorphonuclear leukocytes [PML]); (2) incubation in tissue culture plastic dishes (to remove adherent monocyte/macrophages); and (3) incubation in the presence of high salt (to remove lymphocytes).

Liver transplantation.

A multidisciplinary approach is necessary in addressing the needs of a patient with end-stage liver disease. The development of the liver transplant program at MHI was a natural extension of the transplant and critical care programs already in place. The case report described exemplifies that valuable input from ancillary support groups is necessary for a successful liver transplant program.

Modification of low density lipoproteins by polymorphonuclear cell elastase leads to enhanced uptake by human monocyte-derived macrophages via the low density lipoprotein receptor pathway.

In previous studies we reported that polymorphonuclear cell (PMN) elastase cleaves apoB-100 of human plasma low density lipoprotein (LDL) into seven or eight large Mr fragments (1, Polacek, D., R.E.

In vitro proteolysis of human plasma low density lipoproteins by an elastase released from human blood polymorphonuclear cells.

In vitro incubation of human plasma low density lipoproteins (LDL) with human blood polymorphonuclear cells (PMN) for 1 h at 37 degrees C resulted in an increased (2-4-fold) release into the medium of an enzymatic activity which co-eluted with LDL by column chromatography at physiological ionic strength but dissociated from it in high salt media in an ultracentrifugal field. The release of this enzymatic activity increased with increasing concentration of LDL in the medium and caused the hydrolysis of the LDL apoprotein B100 as indicated by the appearance of 7-8 low molecular weight bands (immunoreactive with anti-LDL) which were not present in the electropherogram of control LDL. The proteolytic activity was identified as an elastase by the following criteria: 1) capacity to hydrolyze the synthetic substrate methoxysuccinyl-Ala-Ala-Pro-Val-4-methylcoumaryl-7-amide known to be specific for the PMN elastase, 2) pattern of apo-B proteolysis identical to that exhibited by pure PMN elastase, 3) inhibition of the proteolysis by the elastase inhibitor methoxysuccinyl-Ala-Ala-Pro-Val-CH2Cl, 4) identity in molecular weight (28,000-30,000) of this activity with a pure preparation of PMN elastase labeled with [3H]diisopropylfluorophosphate.

The enzyme that cleaves apolipoprotein A-II upon in vitro incubation of human plasma high-density lipoprotein-3 with blood polymorphonuclear cells is an elastase.

The proteolytic activity directed against apolipoprotein A-II (apo-A-II) which is released from human blood polymorphonuclear cells (PMN) when they are incubated with human plasma high-density lipoprotein-3 (HDL3) was studied to assess the properties and site specificity of the enzyme. When 125I-apo-A-II-labeled HDL3 was incubated with the PMN protease at 37 degrees C, a complete cleavage of apo-A-II was observed which paralleled the formation of bands of approximately 11,000 and 7,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 7,000-dalton component had the following N-terminal sequence: NH2-Thr-Asp-Tyr-Gly-Lys-Asp-Leu-Met-Glu-Lys.

Factors controlling the release from human blood polymorphonuclear cells in vitro of a proteolytic activity directed against apolipoprotein A-II.

Human high-density lipoprotein class-3 (HDL3) was incubated with freshly isolated blood polymorphonuclear leukocytes (PMN) at 37 and 4 degrees C. At both temperatures the release of proteolytic activity (PA) causing the specific hydrolysis of apo-A-II was dependent on the concentration of HDL3 in the medium. At 37 degrees C, the efflux of PA was linear and no saturation was reached up to an HDL3 protein concentration in the medium of 800 micrograms/ml.

Rapid fractionation of human high density apolipoproteins by high performance liquid chromatography.

A simple and rapid fractionation procedure (30 min) has been developed for the isolation of the major apoproteins from human serum high density lipoproteins by molecular sieving in a high performance liquid chromatographic column. Apo A-I, apoA-II and the C peptides are quantitatively resolved up to a protein load of 3 mg. The technique has also been successfully applied to the final purification of A apoproteins which had been isolated by conventional chromatographic procedures and as a sensitive analytical tool for assessing apoprotein purity.