Saint Louis University

About: Saint Louis University is a education organization based out in St Louis, Missouri, United States. It is known for research contribution in the topics: Population & Health care. The organization has 18927 authors who have published 34895 publications receiving 1267475 citations. The organization is also known as: SLU & St. Louis University.

A Multilevel Analysis of the Vulnerability, Disorder, and Social Integration Models of Fear of Crime

Abstract: The current research tests three conceptual models designed to explain citizens’ fear of crime—vulnerability, disorder, and social integration. These models are assessed for differential impact across the cognitive and affective dimensions of fear of crime. The analysis reported here considers the consecutive and simultaneous influence of individual- and city-level factors using multilevel modeling techniques. Recently collected survey data for 2,599 citizens nested within 21 cities across Washington State provide the empirical evidence for the analysis. Results indicate that the disorder model is best able to explain variation in both the cognitive and affective dimensions of citizens’ fear of crime across cities. The vulnerability and social integration models explain significantly less variation. Further, the vulnerability model lacks directional consistency across the observed dimensions of fear. Societal implications of the research findings are discussed.

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Abstract: Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing.

Metal-induced hepatotoxicity.

Abstract: Figure 3 summarizes several proposed mechanisms of iron- or copper-induced hepatotoxicity. It has long been suspected that free radicals may play a role in iron- and copper-induced cell toxicity because of the powerful prooxidant action of iron and copper salts in vitro. In the presence of available cellular reductants, iron or copper in low molecular weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in wide-ranging impairment in cellular function and integrity. However, cells are endowed with cytoprotective mechanisms (antioxidants, scavenging enzymes, repair processes) that act to counteract the effects of free radical production. Thus, the net effect of metal-induced free radicals on cellular function will depend on the balance between radical production and the cytoprotective systems As a result, there may be a rate of free radical production that must be exceeded before cellular injury occurs. Evidence has now accumulated that iron or copper overload in experimental animals can result in oxidative damage to lipids in vivo, once the concentration of the metal exceeds a threshold level. In the liver, this lipid peroxidation is associated with impairment of membrane-dependent functions of mitochondria (oxidative metabolism) and lysosomes (membrane integrity, fluidity, pH). Although these findings do not prove causality, it seems likely that lipid peroxidation is involved, since similar functional defects are produced by metal-induced lipid peroxidation in these organelles in vitro. Both iron and copper overload impair hepatic mitochondrial respiration, primarily through a decrease in cytochrome c oxidase activity. In iron overload, hepatocellular calcium homeostasis may be impaired through damage to mitochondrial and microsomal calcium sequestration. DNA has also been reported to be a target of metal-induced damage in the liver; this may have consequences as regards malignant transformation. The levels of some antioxidants in the liver are decreased in rats with iron or copper overload, which is also suggestive of ongoing oxidative stress. Reduced cellular ATP levels, lysosomal fragility, impaired cellular calcium homeostasis, and damage to DNA may all contribute to hepatocellular injury in iron and copper overload. There are few data addressing the key issue of whether free radical production is increased in patients with iron or copper overload. Patients with hereditary hemochromatosis have elevated plasma levels of TBA-reactants and increased hepatic levels of MDA-protein and HNE-protein adducts, indicative of lipid peroxidation. Mitochondria isolated from the livers of Wilson disease patients have evidence of lipid peroxidation, and some patients with Wilson disease have decreased hepatic and plasma levels of vitamin E. Additional investigation will be required to fully assess oxidant stress and its potential pathophysiologic role in patients with iron or copper overload.

Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells

Abstract: DNA viruses have evolved elaborate mechanisms to overcome host antiviral defences. In adenovirus-infected cells, programmed cell death (apoptosis) induced by the cytokine tumour necrosis factor (TNF) is inhibited by several adenovirus-encoded proteins. Occupation of the cell-surface receptor Fas, a member of the TNF-receptor superfamily that is expressed on most cell types, triggers apoptosis of that cell. Here we show that the adenovirus RID (for receptor internalization and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis, mediates internalization of cell-surface Fas and its destruction inside lysosomes within the cell. Fas has not previously been shown to be internalized and then degraded. RID also mediates internalization of the receptor for epidermal growth factor, but it does not affect the transferrin receptor or class I antigens of the major histocompatibility complex. Removal of Fas from the surface of adenovirus-infected cells expressing RID may allow infected cells to resist Fas-mediated cell death and thus promote their survival.

Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function.

Abstract: Background: In certain forms of severe heart failure there is sufficient improvement in cardiac function during ventricular assist device (VAD) support to allow removal of the device. However, it is critical to know whether there is sustained recovery of the heart and long-term patient survival if VAD bridging to recovery is to be considered over the option of transplantation. Methods: To determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we retrospectively evaluated 22 patients with non-ischemic heart failure successfully weaned from the Thoratec left ventricular assist device (LVAD) or biventricular assist device (BVAD) after recovery of ventricular function at 14 medical centers. All patients were in imminent risk of dying and were selected for VAD support using standard bridge-to-transplant requirements. There were 12 females and 10 males with an average age of 32 (range, 12-49). The etiologies were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients, for an average duration of 57 days (range, 11-190 days), before return of ventricular function and successful weaning from the device. Post-VAD survival was compared with 43 VAD bridge-to-transplant patients with the same etiologies who underwent cardiac transplantation instead of device weaning. Results: Nineteen of the 22 patients are currently alive. Three patients required heart transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of native hearts (transplant-free survival) post-VAD support is 86% at 1 year and 77% at 5 years, which was not significantly different (p = 0.94) from that of post-VAD transplanted patients, also at 86% and 77%, respectively. Conclusion: Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies and myocarditis is equivalent to that for cardiac transplantation. Recovery of the native heart, which can take weeks to months of VAD support, is the most desirable clinical outcome and should be actively sought, with transplantation used only after recovery of ventricular function has been ruled out.