bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-risk breast lesions: role of multi-parametric DCE-MRI in detection and histopathological upgrade prediction
Authors: Hussein Samar Ahmed , EL-Dhurani Salwa , Abdelnaby Yasmine , Fahim Mohamed , Abdelazeem Hazem , Moustafa Amr Farouk 
Published: September 2022

Abstract
Background
High-risk breast lesions represent 3–21% of all breast lesions and are non-obligate precursors of malignancy. Various studies have evaluated the value of DCE-MRI including DWI and ADC mapping in the detection of high-risk breast lesions, differentiating them from malignant lesions and predicting upgrade risk after surgical excision reducing misdiagnosis and overtreatment. This study is a retrospective review of all image-guided breast biopsy procedures performed in 2021 at our institution, identified 68 patients with histopathologically proven high-risk breast and available MRI examinations with no concurrent ipsilateral malignancy. Image analysis of MRI examinations included morphological criteria, enhancement pattern, dynamic curves, DWI and ADC mapping assessment. Since our knowledge of high-risk breast lesions is still growing, this study is important to evaluate the merits of DCE-MRI in the assessment of high-risk breast lesions, to allow optimization of treatment, better limit it to those women at risk, and avoid overtreatment in women at low risk.

Results
The mean ADC value of high-risk breast lesions was not significantly different from that of malignant breast lesions (p value = 0.015). Non-mass enhancement and type III enhancing curve proved to be significant indicators of high-risk breast lesions upgrade in surgical pathology. Cut-off average ADC value for differentiating upgraded high-risk lesions from non-upgraded high-risk lesions proved 1.24 mm2/sec with sensitivity and specificity of 94 & 100%, respectively.

Discussion
Management of high-risk breast lesions is important in the screening setting, as they are non-obligate precursors of malignancy, and also function as risk indicators. Frequency and upgrade rates of high-risk lesions detected by MRI provide a reference for clinical management. DCE-MRI has a high negative predictive value in predicting the upgrade risk of high-risk lesions. In this study, non-mass enhancement and type III curve were proven to be indicators of high-risk lesion upgrade. Limitations of the study included small number of patients and limited follow-up period.

Conclusions
The use of multi-parametric DCE-MRI including DWI and ADC mapping provides complementary information to detect high-risk breast lesions and predict their upgrade rate.
Therapeutic manipulation of host cell death pathways to facilitate clearance of persistent viral infections
Authors: Cooney James , Allison Cody , Preston Simon , Pellegrini Marc 
Published: September 2022

AbstractMost persistent viral infections can be controlled, but not cured, by current therapies. Abrogated antiviral immunity and stable latently infected cells represent major barriers to cure. This necessitates life-long suppressive antiviral therapy. Achieving a cure for HIV, hepatitis B virus, Epstein Barr-virus, and others, requires novel approaches to facilitate the clearance of infected cells from the host. One such approach is to target host cell death pathways, rather than the virus itself. Here, we summarize recent findings from studies that have utilized therapeutics to manipulate host cell death pathways as a means to treat and cure persistent viral infections.
Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system
Authors: Kunitomi Akane , Hori Toshiyuki , Imura Akihiro , Uchiyama Takashi 
Published: September 2022

Abstract
We investigated whether gp34, the ligand of OX40, expressed on EC is involved in costimulation of T cells. Normal CD4+ T cells were stimulated with anti-CD3-coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of irradiated human umbilical vein endothelial cells (HUVEC). Stimulation of T cells with each of these mitogens results in significant T-cell proliferation only when HUVEC were present, and this proliferation was inhibited markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC. The addition of anti-IL-2R α chain and anti-IL-2R β chain mAbs abolished the costimulatory effects of HUVEC. Thus, the augmentation of T-cell proliferation appears to be attributable to increased IL-2 production. These results suggest that gp34 expressed on HUVEC plays a role in potentiation of T-cell immune response by providing OX40+ T cells with costimulatory signals.
The effects of NO synthase inhibitors on murine collagen-induced arthritis do not support a role of NO in the protective effect of IFN-γ
Authors: Vermeire Kurt , Thielemans Leen , Matthys Patrick , Billiau Alfons 
Published: September 2022

AbstractDBA/1 mice deficient in expressing the interferon-γ (IFN-γ) membrane receptor (IFN-γR KO mice) are more susceptible to collagen-induced arthritis (CIA) than wild-type mice, indicating that endogenous IFN-γ plays a protective role in the pathogenesis of CIA. In IFN-γR KO mice, nitric oxide (NO) production during CIA is impaired. Because NO is known to exert immunosuppressive and anti-inflammatory effects in certain model systems, the protective effect of IFN-γ might be mediated by NO. Here, we tested in wild-type mice whether inhibition of NO production by metabolic inhibitors, aminoguanidine (AG) and L-N-(1-iminoethyl)lysine (L-NIL), could mimic the ablation of the IFN-γ receptor. A high-dose regimen of AG supplied in the drinking water inhibited NO production, disease development, and anticollagen antibody production but was also associated with transient body weight loss. At a dose and time regimen that still inhibited NO production but did not cause body weight loss, AG failed to affect disease scores. Treatment with L-NIL, which more specifically than AG affects inducible NO production, caused a slight increase in anticollagen antibody production although not significantly affecting disease occurrence. These data indicate that the diminished capacity of the IFN-γR KO mice to produce NO following immunization with collagen is unlikely to account for their higher susceptibility to CIA.
Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis
Authors: O’Neill Sean , O’Neill Amanda J , Conroy Eimear , Brady Hugh R , Fitzpatrick John M , Watson R William G 
Published: September 2022

Abstract
Acute pancreatitis (AP) may lead to the development of multiple organ dysfunction syndrome (MODS), especially in severe cases. Resolution of such inflammatory responses is dependent on neutrophil apoptosis. Delays in this apoptotic response are associated with persistent inflammation and subsequent tissue damage. The aim of this study is to determine the effects of AP on neutrophil apoptosis and to investigate the underlying mechanisms involved. Neutrophils and serum were isolated from control (n=10) and from patients with AP (mild, n=35, and severe, n=5). Neutrophil apoptosis was assessed by propidium iodide DNA staining using flow cytometry. Caspase, glutathione-S-transferase (GST), and Mcl-1 protein expression were assessed by SDS-PAGE western blotting. Serum interleukin (IL)-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were measured by ELISA. Neutrophils isolated from patients with AP show a significant delay in spontaneous neutrophil apoptosis. Serum factors contributed to this delay with increases in IL-1β and GM-CSF. Isolated neutrophils were resistant to Fas antibody-induced apoptosis. Caspases represent a central mechanism for spontaneous and Fas antibody-induced neutrophil apoptosis. Procaspase 3 expression was decreased in mild and severe cases, but this effect was independent of serum factors. Increases in GST expression may also contribute to the antiapoptotic effect. Altered caspase expression may represent an additional factor contributing to delayed neutrophil apoptosis. This may contribute to the development of AP and its related complications.
Age-associated increase of basal corticosterone levels decreases ED2high, NF-κBhigh activated macrophages
Authors: Kizaki Takako , Ookawara Tomomi , Iwabuchi Kazuya , Onoé Kazunori , Day Noorbibi K , Good Robert A , Maruyama Naoki , Haga Shukoh , Matsuura Nobuo , Ohira Yoshinobu , Ohno Hideki 
Published: September 2022

Abstract
The proportion of cells with a high density of ED2 (ED2high cells) in peritoneal cells from old rats was significantly lower than that from young rats. The expression of major histocompatibility complex class II (MHC class II) molecules, the antigen presentation, production of interleukin (IL)-1β and IL-6, and nuclear factor-κB activity in ED2high cells were markedly higher than those in cells with a low density of ED2 (ED2low cells), although no significant difference was observed in the expression of MHC class II molecules and the antigen presentation between ED2high cells from young and old rats. Meanwhile, basal corticosterone concentration in serum and glucocorticoid (GC) receptor mRNA expression in peritoneal cells increased significantly in old rats. The proportion of ED2high cells was increased by adrenalectomy in young rats. Furthermore, nuclear translocation of GC receptor was observed in ED2low cells, whereas GC receptor was detected in cytoplasmic extracts from ED2high cells. These results suggest that the decrease in functional ED2high macrophages with age results in the age-associated decline of immune responses, which is regulated, in part, by the basal GC concentration.
LFA-1 (CD11a/CD18) triggers hydrogen peroxide production by canine neutrophils
Authors: Lu Huifang , Ballantyne Christie , Smith C Wayne 
Published: September 2022

AbstractThe respiratory burst of neutrophils stimulated by chemotactic factors is markedly augmented by Mac-1-dependent adhesion such as the interaction of Mac-1 (CD11b/CD18) with intercellular adhesion molecule-1 (ICAM-1; CD54) expressed on the surface of parenchymal cells (e.g., cardiac myocytes). In the current study, we evaluate the hypothesis that lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) can also trigger the respiratory burst in neutrophils. To isolate LFA-1/ICAM-1 interactions from Mac-1/ICAM-1 interactions, full-length chimeric ICAM-1 was developed and expressed in L cells with domains 1 and 2 from canine ICAM-1 and domains 3–5 from human ICAM-1 (C1,2;H3–5). We have shown that canine neutrophils do not bind to human ICAM-1. We demonstrated that chimeric ICAM-1 C1,2;H3–5 supported only LFA-1-dependent adhesion of canine neutrophils and that such adhesion triggered rapid onset of H2O2 production from canine neutrophils. The following seven experimental conditions distinguished LFA-1-dependent H2O2 production from Mac-1-dependent production: It did not require exogenous chemotactic stimulation; H2O2 release was more rapid, but the amount released was &lt;40% of that mediated by Mac-1 adhesion; it was inhibited by anti-CD11a and anti-ICAM-1 antibodies; in contrast to that mediated by Mac-1, it was not inhibited by anti-CD11b antibody, neutrophil inhibitory factor (NIF), or cytochalasin B or H7. Thus, canine neutrophils seem to be able to utilize two members of the β2 integrin family to interact with ICAM-1 and signal H2O2 production, with LFA-1 at an early stage without prior chemotactic stimulation and Mac-1 at a later stage requiring chemotactic stimulation.
Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells
Authors: Yang De , Chen Qian , Chertov Oleg , Oppenheim Joost J 
Published: September 2022

Abstract
Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host defense by disrupting the cytoplasmic membrane of microbes. Here we show that human neutrophil defensins selectively induce the migration of human CD4+/CD45RA+ naive and CD8+, but not CD4+/CD45RO+ memory, T cells. Moreover, human neutrophil defensins are chemotactic for immature human dendritic cells derived from either CD34+ progenitors or peripheral blood monocytes. Upon maturation induced by treatment with tumor necrosis factor α (TNF-α), dendritic cells lose their responsiveness to human neutrophil defensins. The chemotactic effect of human neutrophil defensins on both T and dendritic cells is pertussis toxin-sensitive, suggesting that a Giα protein-coupled receptor is responsible. Human neutrophil defensins are also chemotactic for immature murine dendritic cells. These data suggest that, in addition to their antimicrobial role, human neutrophil defensins also contribute to adaptive immunity by mobilizing T cells and dendritic cells.
Suppression of TNF-α production in human mononuclear cells by an adenosine kinase inhibitor
Authors: Eigler Andreas , Matschke Verena , Hartmann Gunther , Erhardt Simon , Boyle David , Firestein Gary S , Endres Stefan 
Published: September 2022

Abstract
Adenosine exerts potent anti-inflammatory activities through inhibition of cytokine synthesis by activated monocytes. Adenosine is rapidly phosphorylated intracellularly by adenosine kinase. GP515, an adenosine kinase inhibitor, prevents the phosphorylation of adenosine to AMP and thereby locally enhances the adenosine concentration. GP515 has exhibited significant anti-inflammatory effects in several murine models of inflammation. In this study we investigated the effect of GP515 alone and in combination with exogenous adenosine or with rolipram, a phosphodiesterase inhibitor, on tumor necrosis factor α (TNF-α) synthesis in human peripheral blood mononuclear cells (PBMC) or whole blood. Lipopolysaccharide (LPS; 10 ng/mL)-stimulated PBMC were incubated in the absence or presence of these substances. GP515 alone showed a dose-dependent suppression of TNF-α production with an IC50 of 80 μM. The TNF-α-inhibiting effects of adenosine and GP515 were reversed in the presence of the cAMP antagonist (Rp)-cAMPS, supporting the hypothesis of a cAMP-mediated pathway. Combinations of GP515 with either adenosine or rolipram led to an additive inhibition of TNF-α synthesis. These experiments are the first to demonstrate efficacy of an adenosine kinase inhibitor in TNF-α suppression in cells of human origin. The findings form a basis to investigate these strategies in animal models of TNF-α-mediated chronic inflammatory diseases.
Induction of neutrophil death resembling neither apoptosis nor necrosis by ONO-AE-248, a selective agonist for PGE2 receptor subtype 3
Authors: Liu Jiajia , Akahoshi Tohru , Jiang Shixu , Namai Rie , Kitasato Hidero , Endo Hirahito , Kameya Toru , Kondo Hirobumi 
Published: September 2022

Abstract
An increase of intracellular cAMP mediated by prostaglandin E2 (PGE2) has been shown to delay spontaneous apoptosis of neutrophils. It has been demonstrated that a selective agonist for PGE2 receptor subtype 3 (the EP3 receptor) is capable of decreasing cAMP and stimulating phosphoinositide turnover in various types of cells. We investigated the effect of a selective EP3 receptor agonist, ONO-AE-248, on neutrophil viability. ONO-AE-248 rapidly caused a unique form of neutrophil death. The agonist primarily induced morphological changes of the nucleus, including fusion of the lobules, decreased compactness of the chromatin, and blebbing and rupture of the nuclear membrane. This was followed by an increase of plasma membrane permeability and cell lysis. During these processes, neither apoptotic changes such as nuclear condensation, DNA fragmentation, and expression of phospholipid phosphatidylserine on the plasma membrane nor necrotic changes such as chromatin clumping and organelle destruction were apparent in the treated neutrophils. The fatal effect of the agonist might be specific for neutrophils because it failed to promote the rapid death of other types of cells. Although activation of neutrophils by ONO-AE-248 was not evident, experiments using metabolic inhibitors demonstrated that the agonist caused neutrophil death via the activation of protein kinase C in the presence of intracellular ATP. These findings indicated that EP3 receptor-mediated signals might promote a novel form of neutrophil death, which differs from typical apoptosis or necrosis.
Human neutrophil cathepsin G down-regulates LPS-mediated monocyte activation through CD14 proteolysis
Authors: Le-Barillec Karine , Pidard Dominique , Balloy Viviane , Chignard Michel 
Published: September 2022

Abstract
A major property of monocytes/macrophages is to recognize and to be activated by bacterial wall components such as LPS, through membrane receptors including the key element CD14. We demonstrate that CD14 expression is down-regulated, as judged by flow cytometry analysis, upon incubation of human monocytes with purified cathepsin G (CG), a releasable neutrophil serine proteinase. The progressive decrease of CD14 expression due to increasing concentrations of CG highly correlates (P &lt; 0.0001) with the decreased synthesis of tumor necrosis factor α (TNF-α) in response to lipopolysaccharide (LPS). This effect is dependent on the enzymatic activity of CG but is not exerted through an activation of monocytes. Immunoblot analysis reveals that CD14 (Mr = 57,000) is directly cleaved by CG and released into the extracellular medium as a high-Mr species (Mr = 54,000). In this context, incubation of monocytes with activated neutrophils leads to a down-regulation of CD14 expression, a process blocked by a serine proteinase inhibitor. These data suggest a paradoxical anti-inflammatory property for CG.
Expression of α4-integrins on human neutrophils
Authors: Kirveskari Juha , Bono Petri , Granfors Kaisa , Leirisalo-Repo Marjatta , Jalkanen Sirpa , Salmi Marko 
Published: September 2022

Abstract
α4 Integrins are important adhesion molecules mediating binding of lymphocytes, monocytes, and eosinophils to multiple cellular and extracellular ligands. Mature neutrophils have been recently suggested to express α4-integrins as well. We studied whether human neutrophils can synthesize α4-integrins upon activation in vitro or in vivo. Two anti-α4 mAbs, but not multiple subclass-matched non-binding controls, reacted with granulocytes in an inducer and time-dependent manner. Nevertheless, staining with Ig subclass-specific second-stage reagents surprisingly revealed that commercial anti-α4 mAbs contain two distinct Igs, the α4-specific IgG1 and an IgG2a of an unknown specificity. We showed that in vitro inductions used by us and others only induce the binding of nonspecific IgG2a from the commercial HP2/1 to activated neutrophils. By reverse-transcriptase polymerase chain reaction, α4 mRNA was not detectable in purified neutrophils. Our results show that α4 integrin protein and mRNA are absent from normal and stimulated human neutrophils.
β2 Integrin (CD11/CD18)-mediated signaling involves tyrosine phosphorylation of c-Cbl in human neutrophils
Authors: Willeke Thomas , Behrens Sandra , Scharffetter-Kochanek Karin , Gaehtgens Peter , Walzog Barbara 
Published: September 2022

AbstractLeukocyte adhesion molecules of the β2 integrin (CD11/CD18) family mediate cell-cell and cell-substrate interactions of human polymorphonuclear neutrophils (PMN) during their recruitment to sites of inflammation. To elucidate the molecular events that follow extracellular ligand interactions of β2 integrins, protein tyrosine signaling was studied subsequent to integrin engagement by Western blotting technique. Upon adhesion to immobilized fibrinogen, a native ligand of the β2 integrins Mac-1 (CD11b/CD18) and gp150/95 (CD11c/CD18), tyrosine phosphorylation of several proteins including a 120-kDa protein was observed in human PMN. This effect was specific for β2 integrins because it was absent in PMN derived from CD18-deficient mice, which lack any β2 integrin expression. Moreover, no signaling was detectable upon engagement of CD29 and CD61, the β-subunits of the β1 and β3 integrins, respectively, revealing the unique function of the β2 integrins in PMN. By means of immunoprecipitation, the most prominent protein that became tyrosine phosphorylated upon β2 integrin engagement was identified as the 120-kDa protein c-Cbl. The observed signaling was independent of both pertussis toxin-sensitive heterotrimeric G-proteins as well as the small G-protein ras. Inhibition of β2 integrin-mediated signaling by herbimycin A prevented adhesion, shape change, and spreading of PMN to immobilized fibrinogen, demonstrating the biological significance of the observed effect. Together, the present data suggest that the β2 integrins fulfill a unique function among the leukocyte integrins in human PMN by activating an intracellular signal transduction cascade that leads to tyrosine phosphorylation of c-Cbl and allows subsequent adhesion, shape change, and spreading.
Permissive factors for HIV-1 infection of macrophages
Authors: Wahl Sharon M , Greenwell-Wild Teresa , Hale-Donze Hollie , Moutsopoulos Niki , Orenstein Jan M 
Published: September 2022

AbstractImmunodeficiency, the consequence of HIV-1 infection, predisposes the host to opportunistic infections. In turn, opportunistic pathogens influence target cell susceptibility to HIV-1 infection and replication. Although the advent of highly active antiretroviral therapy (HAART) has altered these sequelae, co-infections may prevail in some parts of the world and in failed HAART regimens. Moreover, immune activation as occurs in tonsil and non-infectious mucosal inflammatory lesions may also be associated with proximal sites of viral replication. These connections between enhancement of HIV-1 infection and activation/inflammation warrant further elucidation of the factors promoting permissiveness to HIV-1 infection. Using the opportunistic pathogen Mycobacterium avium as an in vitro model, we demonstrated that co-infection facilitated HIV-1 infection of monocyte-macrophages by multiple pathways. M. avium activated NF-κB, the downstream consequences of which included augmented expression of tumor necrosis factor α and CCR5 receptors, both permissive for sustaining HIV-1 infection. Pronounced viral replication in lymph nodes co-infected with M. avium and HIV-1 paralleled these in vitro findings. Furthermore, reduction in viral burden is associated with treatment of infected or inflamed tissues, underscoring the link between immune activation and viral replication.
HIV-1 genotypes in peripheral blood monocytes
Authors: Zhu Tuofu 
Published: September 2022

Abstract
CD4+ T cells and tissue macrophages are well defined as the major targets for human immunodeficiency virus type 1 (HIV-1) infection and replication, and their infection accounts for many aspects of HIV-1 pathogenesis in vivo. HIV-1 genotype and phenotype in monocytes and their potential roles in pathogenicity in vivo remain unknown. Herein is an overview of our initial work on HIV-1 genotype in purified CD14+ monocytes isolated longitudinally during the course of infection starting from the time of infection. Our data provide evidence for HIV-1 evolution in monocytes and their role as a reservoir of HIV-1 in vivo. A better understanding of HIV-1 in monocytes may greatly help the development of new therapeutic strategies for HIV-1 infection.