bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine
Authors: Ludwig Andreas , Schiemann Florian , Mentlein Rolf , Lindner Buko , Brandt Ernst 
Published: September 2022

AbstractDipeptidyl peptidase IV (DPP IV/CD26) is a costimulatory molecule as well as a protease highly expressed on T cells. Purified DPP IV has been recognized to inactivate peptide hormones, neuropeptides, and some chemokines by cleavage behind a proline residue at the penultimate N-terminal amino acid position. Here, we identified another substrate for DPP IV among the chemokine family: the interferon-inducible T cell α chemoattractant (I-TAC/CXCL11). Using a specific DPP IV inhibitor, we demonstrate that DPP IV is responsible for the cleavage of the chemokine by PHA/IL-2-treated T cells. As PHA/IL-2-treated T cells also express the CXCL11 receptor (CXCR3), we investigated whether truncation of CXCL11 would modulate its biological activity for these cells. Truncated CXCL11 [CXCL11(3–73)] had an eightfold reduced potential to bind and to regulate CXCR3, but was completely inactive in calcium flux and chemotaxis assays. However, consistent with its reduced but still considerable ability to down-regulate CXCR3, truncated CXCL11 desensitized T cell chemotaxis in response to the intact chemokine. Hence, CXCL11-induced T cell recruitment may be regulated by DPP IV-mediated proteolytic inactivation of CXCL11 and furthermore by desensitization of T cells via the degradation product CXCL11(3–73).
Expansion of dendritic cell precursors from human CD34+ progenitor cells isolated from healthy donor blood; growth factor combination determines proliferation rate and functional outcome
Authors: Bontkes Hetty J , de Gruijl Tanja D , Schuurhuis Gert Jan , Scheper Rik J , Meijer Chris J L M , Hooijberg Erik 
Published: September 2022

AbstractCD34+ haematopoietic progenitor cells, which circulate at extremely low frequencies in peripheral blood, are used to generate dendritic cells (DC) in vitro. Here, we describe a method to grow large numbers of DC precursors from these low frequent cells. Different combinations of early acting haematopoietic growth factors supported expansion of CD34+ cells. CD1a+ DC derived from precursors, expanded in fms-like tyrosine kinase-3 ligand (Flt3-L), stem-cell factor (SCF), interleukin (IL)-3, and IL-6, were less potent antigen-presenting cells (APC) compared to CD1a+ DC derived from precursors expanded in Flt3-L, trombopoietine (TPO), and SCF. Furthermore, the latter produced high levels of IL-12 and low levels of IL-10, a cytokine profile favorable for the priming cytotoxic T cells. In contrast, a mean increase of total cell number of 453-fold was obtained with Flt3-L, SCF, IL-3, and IL-6, and this increase was only 38-fold with Flt3-L, TPO, and SCF. Sequential cultures of both cocktails resulted in high numbers of potent APC, which can be useful DC-based cancer vaccines.
Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1
Authors: Xu Liang-Guo , Wu Min , Hu Jiancheng , Zhai Zhonghe , Shu Hong-Bing 
Published: September 2022

AbstractTALL-1 is a member of the tumor necrosis factor family that binds to BCMA, TACI, and BAFF-R, three receptors mostly expressed by mature B lymphocytes. Previous studies have shown that the TALL-1 signaling is critically involved in B cell proliferation, maturation, and progression of lupus-like, autoimmune diseases. In this report, we performed cDNA subtractive hybridization experiments to identify downstream genes up-regulated by TALL-1. These experiments indicated that 10 genes, including interleukin (IL)-10, lymphocyte activation gene-1 (LAG-1), GCP-2, PBEF, ferritin, PIM-2, TFG, CD27 ligand, DUSP5, and archain, were up-regulated at the mRNA level by TALL-1 stimulation in B lymphoma RPMI-8226 cells and/or primary B lymphocytes. We also demonstrated that TALL-1 activated transcription of IL-10 and LAG-1 in a nuclear factor-κB-dependent manner in reporter gene assays. Moreover, our findings indicated BAFF-R, but not TACI, could dramatically up-regulate IL-10 secretion by RPMI-8226 cells. The identification of TALL-1-up-regulated genes will help explain the mechanisms of TALL-1-triggered biological and pathological effects and to identify molecular targets for intervention of lupus-like autoimmune diseases.
Macrophage accumulation at a site of renal inflammation is dependent on the M-CSF/c-fms pathway
Authors: Le Meur Yannick , Tesch Gregory H , Hill Prudence A , Mu Wei , Foti Rita , Nikolic-Paterson David J , Atkins Robert C 
Published: September 2022

AbstractProduction of macrophage-colony stimulating factor (M-CSF), the major macrophage growth factor, is increased in tissues during inflammation. Therefore, w determined whether M-CSF, acting through its receptor c-fms, contributes to macrophage accumulation at a site of tissue injury. Daily treatment with anti-c-fms or control antibody was given to mice with renal inflammation resulting from unilateral ureteric obstruction (UUO). Following UUO, kidney M-CSF mRNA increased in association with macrophage accumulation (days 1, 5, and 10) and local macrophage proliferation (days 5 and 10). Anti-c-fms treatment caused a minor inhibition of monocyte recruitment at day 1, reduced macrophage accumulation by 75% at day 10, but did not affect blood monocyte counts or the CD4 and CD8 lymphocytic infiltrate. Prevention of macrophage accumulation by anti-c-fms treatment was associated with a 90% reduction in local macrophage proliferation at days 5 and 10 without evidence of increased macrophage apoptosis. Therefore, M-CSF/c-fms signaling plays a key role in macrophage accumulation during tissue injury.
The IL-12 response to herpes simplex virus is mainly a paracrine response of reactive inflammatory cells
Authors: Kumaraguru Udayasankar , Rouse B T 
Published: September 2022

AbstractHerpes simplex virus (HSV) infection results in rapid and sustained up-regulation of interleukin (IL)-12, but the primary cellular source of IL-12 after HSV infection is unknown. We demonstrate that this cytokine largely derives from inflammatory cells rather than from productively infected epithelial cells. For optimal IL-12 induction, epithelial cells needed to be infected with replication-competent virus, and cells needed to be able to synthesize proteins. Our results also indicate that HSV-infected cells generate intermediary products that signal recruited inflammatory cells, which themselves were not HSV-infected, to generate IL-12. Possible mechanisms by which infected cells communicate with inflammatory cells to cause IL-12 production are discussed.
IL-13 signal transduction in human monocytes: phosphorylation of receptor components, association with Jaks, and phosphorylation/activation of Stats
Authors: Roy Biswajit , Bhattacharjee Ashish , Xu Bo , Ford Dwayne , Maizel Abby L , Cathcart Martha K 
Published: September 2022

AbstractInterleukin (IL)-13 regulates monocyte function and is a potent stimulator of 15-lipoxygenase expression. In different cell types, the functional IL-13 receptor complex can be comprised of variable protein components and has not been thoroughly examined in human monocytes. Here, we identify the receptor components and upstream signaling events initiated by IL-13 in primary human blood monocytes. Th expression, phosphorylation and associated Jak kinases of the known, variable receptor components, IL-4Rα, IL-2Rγc, IL-13Rα1 and IL-13Rα2, were examined. We determined that IL-4Rα and IL13Rα1 are phosphorylated upon exposure to IL-13. Although IL-2Rγc is also expressed, it is not phosphorylated upon exposure to IL-13. Evaluation of the presence of IL-13Rα2 failed to reveal significant mRNA or protein expression. Earlier, our laboratory showed that IL-13 induced the phosphorylation of Jak2 and Tyk2 in monocytes and that expression of both Jaks was essential for downstream signaling by IL-13. Here, we report that Jak2 is associated with IL-4Rα, and Tyk2 is associated with the IL-13Rα1 component of the IL-13 receptor complex. Additionally, Stat proteins 1α, 3, 5A, 5B, and 6 are phosphorylated in response to IL-13. Further, the nuclear translocation and DNA binding of each of these Stats were induced by IL-13. These data represent the first complete report of the functional IL-13 receptor complex and early signaling events in human monocytes. This information is critical for understanding the IL-13 response of monocytes in inflammation.
Role of the autocrine chemokines MIP-1α and MIP-1β in the metastatic behavior of murine T cell lymphoma
Authors: Menten Patricia , Saccani Alessandra , Dillen Chris , Wuyts Anja , Struyf Sofie , Proost Paul , Mantovani Alberto , Wang Ji Ming , Van Damme Jo 
Published: September 2022

AbstractThe ESb-MP T-cell line is a highly malignant murine lymphoma, which preferentially metastasizes toward the kidney. This could be a result of the local production of monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T expressed and secreted (RANTES), which are chemotactic for ESb-MP cells. Here, we demonstrate that ESb-MP cells are already responsive to the chemotactic activity of macrophage inflammatory protein-1α (MIP-1α) and MIP-1β from 1 ng/ml onward. Moreover, upon stimulation with lipopolysaccharide (LPS) or virus, ESb-MP cells themselves produce significant amounts of MIP-1 (∼200 ng/ml). Indeed, the major autocrine chemoattractants, isolated from ESb-MP cells, were intact MIP-1α and MIP-1β. Pretreatment with LPS or addition of MIP-1 inhibited the in vitro migration of ESb-MP cells toward various chemokines. Moreover, compared with untreated lymphoma cells, LPS-treated cells produced significantly less metastasis in mice. The results represented here suggest that the role of chemokines in attracting tumor cells at secondary sites depends on a balance between autocrine-produced and tissue-derived chemokines. This delicate balance should be considered in the design of antichemokine strategies in different tumor types.
Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses
Authors: Parrish-Novak Julia , Foster Donald C , Holly Richard D , Clegg Christopher H 
Published: September 2022

AbstractInterleukin (IL)-21 was recently discovered using a functional cloning approach based on expression of its receptor. It is similar in domain organization and primary sequence to IL-2 and IL-15. Like these cytokines, IL-21 uses the common γ chain of the IL-2/15 receptor, which forms a heterodimeric receptor complex with IL-21R. IL-21 is produced by activated T cells, and it influences proliferation of T and B cells and cytolytic activity of natural killer cells. The elucidation of the unique biological effects of IL-21 represents an intense area of interest in current cytokine biology.
Disruption of the Nramp1 (also known as Slc11a1) gene in Kupffer cells attenuates early-phase, warm ischemia-reperfusion injury in the mouse liver
Authors: Wyllie Samuel , Seu Philip , Gao Feng Qin , Gros Phillippe , Goss John A 
Published: September 2022

AbstractAs the natural resistance-associated macrophage protein 1 Nramp1 (also known as Slc11a1) modulates Kupffer cell (KC) activation, and KC are responsible for the early phase of warm ischemia/reperfusion (I/R) to the liver, we hypothesized that livers of Nramp1−/− mice will be protected from early-phase I/R injury compared with livers of Nramp1+/+ mice. To test our hypothesis, we induced partial warm ischemia to the livers of Nramp1+/+ and Nramp1−/− mice for 45 min of by clamping the hilum of the median and left lateral lobes, followed by 30 or 60 min of reperfusion. Plasma glutamate oxaloacetate transaminase (pGOT) activity and tumor necrosis factor α (TNF-α) levels were measured, and liver sections were stained for polymorphonuclear leukocyte (PMN) accumulation. After 45 min of ischemia and 30/60 min of reperfusion of Nramp1+/+ and Nramp1−/− mice livers, we found significant increases in plasma pGOT activity and TNF-α levels in Nramp1+/+ mice at 30 and 60 min of reperfusion, respectively, compared with sham controls and all Nramp1−/− mice. A significant accumulation of PMNs was also found in livers of Nramp1+/+ mice at 60 min of reperfusion compared with all other groups. We have shown that disruption of the Nramp1 gene attenuates I/R injury to the mouse liver during the early phase of warm I/R injury. An increased understanding of the role played by Nramp1 is particularly important in the liver, as this organ is subjected to a wide variety of injuries during hemorrhagic shock, partial resections, and transplantation.
Role of CD80, CD86, and CTLA4 on mouse CD4+ T lymphocytes in enhancing cell-cycle progression and survival after activation with PMA and ionomycin
Authors: Mukherjee Sambuddho , Maiti Prasanta K , Nandi Dipankar 
Published: September 2022

AbstractCell surface interactions between the T cell costimulatory receptors, CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA4), with their cognate ligands, CD80 and CD86, on antigen-presenting cells play an important role in T cell activation. Although CD80 and CD86 are induced on T cells after activation, not much is known about their role in modulating T cell function. We show that CD80, CD86, and CTLA4 are induced on purified CD4+ T cells after in vitro activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and they play an essential role for proliferation and survival. Blockade of CTLA4-CD80/CD86 interactions greatly reduces PMA and ionomycin-mediated mouse CD4+ T cell activation. The three key features of this inhibition of activation are: First, late events in T cell activation (after 18 h) are affected; second, these cells do not undergo anergy; and third, CD4+CD25+ regulatory T cells are not responsible. Activation of T cells with PMA and ionomycin together with CTLA4-CD80/CD86 blockade results in decreased induction of CD25 and Bcl-XL, reduced interleukin (IL)-2, and enhanced transforming growth factor-β (TGF-β) production. Furthermore, extended CTLA4-CD80/CD86 blockade results in decreased cell-cycle progression and enhanced apoptosis in a large proportion of cells. This inhibition of T cell proliferation can be rescued completely with anti-CD28 or IL-2 and partially with TGF-β antagonists. This study reveals a functional role for CD80, CD86, and CTLA4 on CD4+ T lymphocytes and sheds light on the mechanisms by which these molecules enhance activation and survival with PMA and ionomycin.
Cyclosporin A inhibits dendritic cell maturation promoted by TNF-α or LPS but not by double-stranded RNA or CD40L
Authors: Duperrier K , Farre A , Bienvenu J , Bleyzac N , Bernaud J , Gebuhrer L , Rigal D , Eljaafari A 
Published: September 2022

AbstractHere, we investigated the influence of cyclosporin A (CsA) on dendritic cell (DC) generation. With this aim, human DC were propagated from monocytes in serum-free medium with granulocyte macrophage-colony stimulating factor and interleukin-4. DC were then exposed to tumor necrosis factor α (TNF-α) for maturation. Our results show that CsA does not impair commitment of monocytes into DC, as assessed by loss of CD14 and increase of CD40 and CD1a. However, TNF-α-induced DC maturation was affected, as CsA-treated DC expressed lower levels of human leukocyte antigen and costimulatory molecules but sustained levels of CD1a, and less DC expressed DC-lysosomal-associated-membrane-protein (LAMP) and CD83. Accordingly, CsA inhibited the allostimulatory and accessory cell functions of DC. Surprisingly, when other maturation stimuli were used, we observed that CsA significantly inhibited maturation induced by lipopolysaccharides but not by polyribocytidylic acid or CD40 ligand, as assessed by DC phenotype and functions. Therefore, our results indicate that CsA may differentially affect DC maturation.
Chronic ethanol consumption by mice results in activated splenic T cells
Authors: Song Kejing , Coleman Ruth A , Zhu Xiaoyan , Alber Carol , Ballas Zuhair K , Waldschmidt Thomas J , Cook Robert T 
Published: September 2022

AbstractPrevious studies have shown that T cells from human alcoholics overexpress activation or memory markers such as human leukocyte antigen-DR, CD45RO, CD57, and CD11b and may have reduced levels of CD62L. In those studies, we demonstrated that the increased CD57+ T cell population rapidly produces interferon-γ (IFN-γ) and tumor necrosis factor α, independent of a second signal requirement, consistent with an increased effector T cell population. In contrast to the length of alcohol abuse by human alcoholics, most work with mice has involved 2-week ethanol exposures or less, which result in decreased IFN-γ responses. In the present work, we have evaluated C57Bl/6 or BALB/c mice, which were administered 20% w/v ethanol in water for 3–13 weeks. In these mice, rapid cytoplasmic IFN-γ expression by T cells after stimulation through the T cell receptor was significantly increased versus normals. Studies of surface-activation markers showed that T cells from chronically ethanol-fed mice had reduced CD62L expression and an increased percentage of CD44hi T cells. The CD44hi subset was largely second signal-independent for secreted IFN-γ and interleukin (IL)-4 production at early times after stimulation. The enriched T cells of chronic ethanol mice secreted more IFN-γ and IL-4 than controls and equivalent IL-2 at early times after stimulation (6–24 h). The overall results support the concept that in humans and mice, chronic alcohol exposure of sufficient duration results in T cell activation or sensitization in vivo and an increased percentage of the effector/memory subset.
Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells
Authors: Kitaichi Nobuyoshi , Kotake Satoshi , Morohashi Taiki , Onoé Kazunori , Ohno Shigeaki , Taylor Andrew W 
Published: September 2022

AbstractTo evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)-susceptible mice with anti-CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti-CD161c antibodies deleted NK cells from the peripheral blood of EAU-susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti-CD161c antibody when compared with T cells from control mice. Although mice treated with anti-CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti-CD161c-treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti-CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1+ NK cells.
The Double Agent: NOB / RD
Authors: Davidson Michael 
Published: September 2022

Abstract
This essay explores the close relationship between the poet Robert Duncan and Norman O. Brown. Their long friendship and shared intellectual interests were generative for both, allowing Brown at one point to remark that the “poetry of Robert Duncan had made the writing of Love's Body possible.” Duncan responded in kind by featuring Brown in “Santa Cruz Propositions,” written while the poet was in residence at the University of California, Santa Cruz. That poem draws on Brown's theories of Eros as a daemonic power to criticize his (Duncan's) old friend, Denise Levertov, whose anti-war poetry he felt had grown shrill and hectoring. At the same time, the poem attempts to draw out Brown's Dionysian, poetic potential. Duncan made Norman O. Brown an unwitting co-conspirator in this effort by attempting to reveal the naked poet beneath the academic robes. Much of the essay is based on correspondence between the two figures.
Management of Chronic Subdural Hematoma: A Systematic Review and Component Network Meta-analysis of 455 Studies With 103 645 Cases
Authors: Henry Jack , Amoo Michael , Kissner Malia , Deane Thomas , Zilani Gulam , Crockett Matthew T. , Javadpour Mohsen 
Published: September 2022

BACKGROUND:Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment.OBJECTIVE:To assess and compare the risk of recurrence, morbidity, and mortality across various treatments for CSDH.METHODS:A systematic review and meta-analysis was performed. PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched from January 01, 2000, to July 07, 2021. The primary outcome was recurrence, and secondary outcomes were morbidity and mortality. Component network meta-analyses (CNMAs) were performed for surgical and medical treatments, assessing recurrence and morbidity. Incremental risk ratios (iRRs) with 95% CIs were estimated for each component.RESULTS:In total, 12 526 citations were identified, and 455 studies with 103 645 cases were included. Recurrence occurred in 11 491/93 525 (10.8%, 95% CI 10.2-11.5, 418 studies) cases after surgery. The use of a postoperative drain (iRR 0.53, 95% CI 0.44-0.63) and middle meningeal artery embolization (iRR 0.19, 95% CI 0.05-0.83) reduced recurrence in the surgical CNMA. In the pharmacological CNMA, corticosteroids (iRR 0.47, 95% CI 0.36-0.61) and surgical intervention (iRR 0.11, 95% CI 0.07-0.15) were associated with lower risk. Corticosteroids were associated with increased morbidity (iRR 1.34, 95% CI 1.05-1.70). The risk of morbidity was equivalent across surgical treatments.CONCLUSION:Recurrence after evacuation occurs in approximately 10% of cSDHs, and the various surgical interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials.
Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms
Authors: El Naamani Kareem , Saad Hassan , Chen Ching-Jen , Abbas Rawad , Sioutas Georgios S. , Amllay Abdelaziz , Yudkoff Clifford J. , Carreras Angeleah , Sambangi Abhijeet , Hunt Adam , Jain Paarth , Dougherty Jaime , Tjoumakaris Stavropoula I. , Gooch Michael R. , Herial Nabeel A. , Rosenwasser Robert H. , Zarzour Hekmat , Schmidt Richard F. , Jabbour Pascal M. 
Published: September 2022

BACKGROUND:The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce.OBJECTIVE:To compare the outcomes of PED and FRED in the treatment of intracranial aneurysms.METHODS:This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication.RESULTS:The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%;P= .017) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%;P= .573), and the rate of in-stent stenosis was approximately double in the FRED cohort (15.2% vs 6.9%;P= .172).CONCLUSION:Compared with PED, FRED offers modest 6-month occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity.