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We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lipolysis by using recombinant adenovirus to express native and catalytically inactive HL (HL-145G) in apolipoprotein (apo)E-deficient mice characterized by increased plasma concentrations of apoB-48-containing remnants. In the absence of apoE, the mechanisms by which apoB-48-containing remnants are taken up by either low density lipoprotein (LDL)-receptor or LDL-receptor-related protein (LRP) remain unclear. Overexpression of either native or catalytically inactive HL in apoE-deficient mice led to similar reductions (P > 0.5) in the plasma concentrations of cholesterol (41% and 53%) and non high density lipoprotein (HDL)-cholesterol (41% and 56%) indicating that even in the absence of lipolysis, HL can partially compensate for the absence of apoE in this animal model. Although the clearance of [3H]cholesteryl ether from VLDL was significantly increased (approximately 2-fold; P < 0.02) in mice expressing native or inactive HL compared to luciferase controls, the fractional catabolic rates (FCR) of [125I-labeled] apoB- very low density lipoprotein (VLDL) in all three groups of mice were similar (P > 0.4, all) indicating selective cholesterol uptake. Hepatic uptake of [3H]cholesteryl ether from VLDL was greater in mice expressing either native HL (87%) or inactive HL-145G (72%) compared to luciferase controls (56%). Our combined findings are consistent with a role for HL in mediating the selective uptake of cholesterol from remnant lipoproteins in apoE-deficient mice, independent of lipolysis. These studies support the concept that hepatic lipase (HL) may serve as a ligand that mediates the interaction between remnant lipoproteins and cell surface receptors and/or proteoglycans. We hypothesize that one of these pathways may involve the interaction of HL with cell surface receptors, such as scavenger receptor (SR)-BI, that mediate the selective uptake of cholesteryl esters.—Amar, M. J. A., K. A. Dugi, C. C. Haudenschild, R. D. Shamburek, B. Foger, M. Chase, A. Bensadoun, R. F. Hoyt, Jr., H. B. Brewer, Jr., and S. Santamarina-Fojo. Hepatic lipase facilitates the selective uptake of cholesteryl esters from remnant lipoproteins in apoE-deficient mice. J. Lipid Res. 1998. 39: 2436–2442.

Abstract: Background: CD4+CD25HiFoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long‐term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long‐term baboon recipients who have received genetically modified cardiac xenografts from pig donors. Methods: Heterotopic cardiac xenotransplantation was performed on baboons using hearts obtained from GTKO.hCD46 (n = 8) and GTKO.hCD46.TBM (n = 5) genetically modified pigs. Modified immunosuppression regimen included antithymocyte globulin (ATG), anti‐CD20, mycophenolate mofetil (MMF), cobra venom factor (CVF), and costimulation blockade (anti‐CD154/anti‐CD40 monoclonal antibody). FACS analysis was performed on PBLs labeled with anti‐human CD4, CD25, and FoxP3 monoclonal antibodies (mAb) to analyze the percentage of Treg cells in six baboons that survived longer than 2 months (range: 42‐945 days) after receiving a pig cardiac xenograft. Results: Total WBC count was low due to immunosuppression in baboons who received cardiac xenograft from GTKO.hCD46 and GTKO.hCD46.hTBM donor pigs. However, absolute numbers of CD4+CD25HiFoxP3 Treg cells in PBLs of long‐term xenograft cardiac xenograft surviving baboon recipients were found to be increased (15.13 ± 1.50 vs 7.38 ± 2.92; P < .018) as compared to naïve or pre‐transplant baboons. Xenograft rejection in these animals was correlated with decreased numbers of regulatory T cells. Conclusion: Our results suggest that regulatory T (Treg) cells may contribute to preventing or delaying xenograft rejection by controlling the activation and expansion of donor‐reactive T cells, thereby masking the antidonor immune response, leading to long‐term survival of cardiac xenografts. [ABSTRACT FROM AUTHOR]

Background: Both intense endurance training and valvular regurgitation place a volume load on the right and left ventricles, potentially leading to dilation, but their effects in combination are not well-known. Purpose: The purpose of this case series is to describe the combined volume load of intense endurance athletic training and regurgitant valvular disease as well as the challenging assessment of each component's cardiovascular effect. Methods: In this article, the clinical course of three elite endurance athletes with congenital valvular disease were reviewed. Results: A swimmer with aortic regurgitation, a cyclist with aortic regurgitation, and a cyclist with pulmonary regurgitation were found to have severe dilation of the associated ventricles despite continuing to train at an elite level without symptoms. Conclusions: Because of the cumulative effects of endurance training and valvular regurgitation, each athlete manifested ventricular dilation out of proportion to their valvular disease and symptoms. Although the effects of congenital valvular disease and athletic remodeling on ventricular dilation have been thoroughly studied individually, their cumulative effect is not well understood. This complicates the assessment of athletes with valvular regurgitation and underscores the need for athlete-specific recommendations for valve replacement. [ABSTRACT FROM AUTHOR]

The article discusses research that analyzed the development of modern initiatives to protect athletes from sudden death from a historical and literary perspective. Topics covered include the definition and origins of ancient and modern sport, the association of sport and the risk of death in literature and sudden cardiac death in modern athletics.

Objectives We sought to investigate if autologous freshly isolated regulatory T cells (Tregs) provide a protective and supportive role when cotransplanted with mesenchymal stem cells (MSCs). Methods In a porcine model of chronic ischemia, autologous MSCs were isolated and expanded ex vivo for 4 weeks. Autologous Treg cells were freshly isolated from 100 mL peripheral blood and purified by fluorescence-activated cell sorting. MSCs and Treg cells were then cotransplanted into the chronic ischemic myocardium of Yorkshire pigs by direct intramyocardial injection (1.2 x 108 MSCs plus an average of 1.5 million Treg cells in 25 injection sites). Animals were killed 6 weeks postinjection to study the fate of the cells and compare the effect of combined MSCs + Treg cells transplantation versus MSCs alone. Results The coinjection of MSCs along with Tregs was safe and no deleterious side effects were observed. Six weeks after injection of the cell combination, spherical MSCs clusters with thin layer capsules were found in the injected areas. In animals treated with MSCs only, the MSC clusters were less organized and not encapsulated. Immunofluorescent staining showed CD25+ cells among the CD90+ (MSC marker) cells, suggesting that the injected Treg cells remained present locally, and survived. Factor VIII+ cells were also prevalent suggesting new angiogenesis. We found no evidence that coinjections were associated with the generation of cardiac myocytes. Conclusions The cotransplantation of Treg cells with MSCs dramatically increased the MSC survival rate, proliferation, and augmented their role in angiogenesis, which suggests a new way for future clinical application of cell-based therapy. [ABSTRACT FROM AUTHOR]

Racism is a term on which a great deal of discourse does and should turn in all realms of social work theory, practice, policy, and research. Because it is a concept heavily freighted with multiple and conflicting interpretations and used in a wide variety of ways, the idea and action of racism is not easy to teach or learn in a simple and straightforward manner. It is a term the meaning of which has been the subject of so much argument and mutation that its utility as a clear and reliable descriptor of a crucial form of ideology or behavior is less than certain. In this article, an analysis of the dispute over the proper definition of racism is undertaken, and an approach to teaching about the term is offered in an effort to provide both teachers and students with a clear, consistent, and useful understanding of this important and challenging phenomenon. [ABSTRACT FROM AUTHOR]

Objective. Significant structural changes occur in the rat vagina in response to sex steroid hormone deprivation and replacement. However, the mechanism by which these changes occur is not clearly understood and our current hypothesis is that these effects are mediated, at least in part, by the expression of sex steroid hormone receptors. The goal of this study was to assess changes in steroid hormone receptor expression and distribution in response to sex steroid hormone deprivation and administration. Methods. Female rats were either kept intact (controls) or ovariectomized. Ovariectomized animals were treated with vehicle, estradiol, testosterone, progesterone, or hormone combinations. Using immunohistochemistry, hormone receptor distribution was assessed in all layers of the vaginal wall. Results. After ovariectomy, estrogen receptor alpha (ERα) was up-regulated and progesterone receptor (PR) was down-regulated. Estradiol replacement restored these ovariectomy-induced changes, and this effect was dose-dependent. Androgen receptor (AR) expression was unaffected by ovariectomy or estradiol replacement. However, testosterone treatment resulted in increased AR density in the muscularis. Addition of either testosterone or progesterone to estradiol mitigated but did not abolish the effects of estradiol alone. Conclusion. Estradiol down-regulated ERα and up-regulated PR expression in the vagina, suggesting this may be a mechanism to prevent continued proliferation of the epithelium by surges of estradiol during the estrous cycle. Pessina MA, Hoyt RF, Goldstein I, and Traish AM. Differential regulation of the expression of estrogen, progesterone, and androgen receptors by sex steroid hormones in the vagina: Immunohistochemical Studies. J Sex Med 2006;3:804–814. [ABSTRACT FROM AUTHOR]

Evaluates the effects of ATP binding cassette transporter A1 on the development of diet-induced atherosclerosis. Evidence of spontaneous lesion formation; Role in macrophage cholesterol metabolism and atherogenesis; Modulation of low density lipoprotein.

Determines the manometric, ultrastructural, radiographic and physiological consequences of retrograde biliary infusion in normostatic and cholestatic mice. Intraluminal pressure changes that are dependent on infusion rate and volume caused by retrograde biliary infusion; Infusion viscosity's determination of intraluminal pressure changes.

Explores the possible effects of H+ and HCO3+ on pulmonary endocrine cells (PEC) in vitro using a fetal rat lung organ culture system. Pharmacological and physiological regulation of PEC in the absence of their innervation; Calcitonin gene-related peptide (CGRP)-like immunoreactive material; Potential Physiologic functions for CGRP.

Discusses the findings and anticipated outcomes of the seventh assembly of the World Council of Churches (WCC) in Canberra. Concerns of theology for discussion; Challenges of charismatic and pentecostal movements and African Independent churches for the WCC; Need of including the Aboriginal concept of theology and spirituality.

Transient cardiac ischemia activates cell survival signaling, conferring subsequent ischemia tolerance to the heart. This biological phenomenon, teemed ischemic preconditioning, results in improved clinical outcome and attenuated infarct size following myocardial infarction. To explore genomic modifications underpinning this ischemia tolerance, we delineated the regulation and function of the cardiac enriched mitochondrial uncoupling proteins 2 and 3 during delayed ischemic preconditioning in the rat. Cardiac transcripts of genes encoding uncoupling proteins 2 and 3 are upregulated in parallel with infarct size reduction in preconditioned hearts. Mitochondria isolated from preconditioned hearts exhibit an augmented inducible proton leak. In parallel, following anoxia-reoxygenation these mitochondria generate less hydrogen peroxide compared with non-preconditioned mitochondria. Preconditioning in rat cardiac derived myoblasts is abolished following uncoupling protein-2 depletion by RNA-interference. RNAi of uncoupling protein-3 partially attenuates the capacity to precondition these cells. Functional characterization of anoxia and reoxygenation tolerance following uncoupling protein 2 or 3 and combined 2 and 3 RNAi shows the largest reduction in viability follows depletion of both homologues. Uncoupling protein-2 depletion alone significantly attenuates anoxia-reoxygenation tolerance but uncoupling protein-3 depletion does not reduce anoxia tolerance. In parallel combined uncoupling protein depletion and isolated uncoupling protein-2 depletion augments ROS production in viable cardiomyocytes following anoxia-reoxygenation. Concurrent anti-oxidant administration ameliorates the uncoupling protein-depleted anoxia-susceptible phenotype. In conclusion, mitochondrial uncoupling proteins are necessary components of ischemia tolerance and function as components of the cellular antioxidant defense program. In the cytoprotective hierarchy, uncoupling protein-2 appears to play a greater role than uncoupling protein-3 in modulating ischemia/anoxia tolerance in heart-derived cells. [ABSTRACT FROM AUTHOR]

Pervasive SARS-CoV-2 infections in humans have led to multiple transmission events to animals. While SARS-CoV-2 has a potential broad wildlife host range, most documented infections have been in captive animals and a single wildlife species, the white-tailed deer. The full extent of SARS-CoV-2 exposure among wildlife communities and the factors that influence wildlife transmission risk remain unknown. We sampled 23 species of wildlife for SARS-CoV-2 and examined the effects of urbanization and human use on seropositivity. Here, we document positive detections of SARS-CoV-2 RNA in six species, including the deer mouse, Virginia opossum, raccoon, groundhog, Eastern cottontail, and Eastern red bat between May 2022-September 2023 across Virginia and Washington, D.C., USA. In addition, we found that sites with high human activity had three times higher seroprevalence than low human-use areas. We obtained SARS-CoV-2 genomic sequences from nine individuals of six species which were assigned to seven Pango lineages of the Omicron variant. The close match to variants circulating in humans at the time suggests at least seven recent human-to-animal transmission events. Our data support that exposure to SARS-CoV-2 has been widespread in wildlife communities and suggests that areas with high human activity may serve as points of contact for cross-species transmission., (© 2024. The Author(s).)