bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatoprotective Effect of Nigella Sativa Linn (Kalajira) On Paracetamol-induced Liver Damage
Authors: Pal Dipali Rani , Nahar Shamusn , Roy Kanta , Talukder Shah Alam , Hossain Md. Motahar , Paul Paritosh Chandra , Eva Eliza Omar 
Published: April 2014

Paracetamol is the widely used non-steroidal anti-inflammatory drugs for the treatment of mild to moderate pain. It causes hepatotoxicity in therapeutic dose for prolonged time. It can induce centrilobular hepatic necrosis in large over doses. Nigella sativa (kalajira) is a medicinal plant has a protective role against hepatotoxicity. Therefore, the present study was designed to observe the protective role of Nigella sativa on paracetamol induced liver damage biochemically in Long Evans rats. The experiment was carried out in the Department of Anatomy, Dhaka Medical college, in the period of July 2003 to June 2004. Sixty matured Long Evans rats of either sex, age of 10-12 weeks and weighing between 150-200 gm were used in this study. They were divided into four equal groups. Group A was vehicle (distilled water) control group, Group B was Nigella oil treated group, Group C was paracetamol treated group and Group D was Paracetamol & Nigella sativa oil treated group. Paracetamol in a single dose of 3gm/kg body weight orally causes hepatotoxicity which was assessed bio-chemically. Nigella sativa oil at a dose of 800mg/kg body weight was administered orally for 4 weeks. It was found that significant elevation of serum alanine aminotransferase, serum aspartate aminotransferase, serum alkaline phosphatase and serum bilirubin level in paracetamol treated group. It was observed that 4 weeks oral treatment of Nigella sativa oil in Group D, decrease the level of serum alanine aminotransferase, serum aspartate aminotransferase, serum alkaline phosphatase and serum bilirubin. The result revealed that Nigella sativa oil able to give protection against paracetamol induced liver damage. However, more sophisticated biochemical studies like glutathione content and malondialdehyde level should be studied further. DOI: http://dx.doi.org/10.3329/bmj.v40i3.18677 Bangladesh Medical Journal 2011 Vol.40(3):52-54
Cutting Edge: Activation of the p38 Mitogen-Activated Protein Kinase Signaling Pathway Mediates Cytokine-Induced Hemopoietic Suppression in Aplastic Anemia
Authors: Verma Amit , Deb Dilip K. , Sassano Antonella , Kambhampati Suman , Wickrema Amittha , Uddin Shahab , Mohindru Mani , Van Besien Koen , Platanias Leonidas C. 
Published: April 2014

Abstract
Myelosuppressive cytokines, in particular IFN-γ and TNF-α, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-γ and TNF-α in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-γ and TNF-α on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.
Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4
Authors: Guillot Loïc , Balloy Viviane , McCormack Francis X. , Golenbock Douglas T. , Chignard Michel , Si-Tahar Mustapha 
Published: April 2014

AbstractThe collectin surfactant protein-A (SP-A) is involved in the innate host defense and the regulation of inflammatory processes in the lung. In this work we investigated the molecular mechanisms related to the immunostimulatory activity of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary cells. We demonstrate that SP-A-induced activation of the NF-κB signaling pathway and up-regulation of cytokine synthesis such as TNF-α and IL-10 are critically dependent on the TLR4 functional complex. These findings support the concept that TLR4 is a pattern recognition receptor that signals in response to both foreign pathogens and endogenous host mediators.
Cutting Edge: Urease Release by Helicobacter pylori Stimulates Macrophage Inducible Nitric Oxide Synthase
Authors: Gobert Alain P. , Mersey Benjamin D. , Cheng Yulan , Blumberg Darren R. , Newton Jamie C. , Wilson Keith T. 
Published: April 2014

Abstract
Inducible NO synthase (iNOS) expression and production of NO are both up-regulated with Helicobacter pylori infection in vivo and in vitro. We determined whether major pathogenicity proteins released by H. pylori activate iNOS by coculturing macrophages with wild-type or mutant strains deficient in VacA, CagA, picB product, or urease (ureA−). When filters were used to separate H. pylori from macrophages, there was a selective and significant decrease in stimulated iNOS mRNA, protein, and NO2− production with the ureA− strain compared with wild-type and other mutants. Similarly, macrophage NO2− generation was increased by H. pylori protein water extracts of all strains except ureA−. Recombinant urease stimulated significant increases in macrophage iNOS expression and NO2− production. Taken together, these findings indicate a new role for the essential H. pylori survival factor, urease, implicating it in NO-dependent mucosal damage and carcinogenesis.
The Protein Product of the Tumor Suppressor Gene, Melanoma Differentiation-Associated Gene 7, Exhibits Immunostimulatory Activity and Is Designated IL-24
Authors: Caudell Eva G. , Mumm John B. , Poindexter Nancy , Ekmekcioglu Suhendan , Mhashilkar Abner M. , Yang Xiaohong Helena , Retter Mark W. , Hill Paul , Chada Sunil , Grimm Elizabeth A. 
Published: April 2014

Abstract
The melanoma differentiation-associated gene 7 (mda-7) has been studied primarily in the context of its tumor suppressor activity. Although mda-7 has been designated as IL-24 based on its gene location in the IL-10 locus and its mRNA expression in leukocytes, no functional evidence supporting this cytokine designation exists. To further characterize MDA-7/IL-24 expression patterns in the human immune system, MDA-7/IL-24 protein levels were examined in human PBMC. MDA-7/IL-24 was detected in PHA- and LPS-stimulated whole PBMC lysate by Western blot and in PHA-activated CD56 and CD19 subsets by immunohistochemistry. The biological function of MDA-7/IL-24, secreted from Ad-MDA7-transfected HEK 293 cells, was assessed by examining the effect of MDA-7/IL-24 on the cytokine secretion profile of PBMC. Within 48 h MDA-7/IL-24 induced secretion of high levels of IL-6, TNF-α, and IFN-γ and low levels of IL-1β, IL-12, and GM-CSF from human PBMC as measured by ELISA. The MDA-7/IL-24-mediated induction of these Th1-type cytokines was inhibited by the addition of IL-10 to the PBMC cultures, suggesting that these two related protein family members may provide antagonistic functions. Therefore, because human blood leukocytes can be stimulated to produce MDA-7/IL-24, as well as respond to MDA-7/IL-24 by expressing secondary cytokines, MDA-7/IL-24 has the expression profile and major functional attributes that justify its designation as an IL.
Viral Abrogation of Stem Cell Transplantation Tolerance Causes Graft Rejection and Host Death by Different Mechanisms
Authors: Forman Daron , Welsh Raymond M. , Markees Thomas G. , Woda Bruce A. , Mordes John P. , Rossini Aldo A. , Greiner Dale L. 
Published: April 2014

AbstractTolerance-based stem cell transplantation using sublethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. We have shown that mouse bone marrow recipients treated with sublethal irradiation plus transient blockade of the CD40-CD154 costimulatory pathway develop permanent hematopoietic chimerism across allogeneic barriers. We now report that infection with lymphocytic choriomeningitis virus at the time of transplantation prevented engraftment of allogeneic, but not syngeneic, bone marrow in similarly treated mice. Infected allograft recipients also failed to clear the virus and died. Postmortem study revealed hypoplastic bone marrow and spleens. The cause of death was virus-induced IFN-αβ. The rejection of allogeneic bone marrow was mediated by a radioresistant CD8+TCR-αβ+NK1.1− T cell population. We conclude that a noncytopathic viral infection at the time of transplantation can prevent engraftment of allogeneic bone marrow and result in the death of sublethally irradiated mice treated with costimulation blockade. Clinical application of stem cell transplantation protocols based on costimulation blockade and tolerance induction may require patient isolation to facilitate the procedure and to protect recipients.
CD36 Is Differentially Expressed by CD8+ Splenic Dendritic Cells But Is Not Required for Cross-Presentation In Vivo
Authors: Belz Gabrielle T. , Vremec David , Febbraio Maria , Corcoran Lynn , Shortman Ken , Carbone Francis R. , Heath William R. 
Published: April 2014

Abstract
Cross-presentation allows the processing of Ags from donor cells into the MHC class I presentation pathway of dendritic cells (DCs). This is important for the generation of cytotoxic T cell immunity and for induction of self tolerance. Apoptotic cells are reported to be efficient targets for cross-presentation, and in vitro studies using human DCs have implicated CD36 in their capture. In support of a role for CD36 in cross-presentation, we show that this molecule is differentially expressed by CD8+ splenic DCs, which previously have been identified as responsible for cross-presentation in the mouse. Three different cross-presentation models were examined for their dependence on CD36. These included cross-priming to OVA-coated spleen cells and cross-tolerance to OVA transgenically expressed in the pancreatic islet β cells under constitutive conditions or during β cell destruction. In these models, CD36 knockout DCs were equivalent to wild-type DCs in their capacity to cross-present either foreign or self Ags, indicating that CD36 is not essential for cross-presentation of cellular Ags in vivo.
Transendothelial Migratory Pathways of Vδ1+TCRγδ+ and Vδ2+TCRγδ+ T Lymphocytes from Healthy Donors and Multiple Sclerosis Patients: Involvement of Phosphatidylinositol 3 Kinase and Calcium Calmodulin-Dependent Kinase II
Authors: Poggi Alessandro , Zocchi Maria Raffaella , Carosio Roberta , Ferrero Elisabetta , Angelini Daniela F. , Galgani Simona , Caramia Maria D. , Bernardi Giorgio , Borsellino Giovanna , Battistini Luca 
Published: April 2014

AbstractWe have previously reported that the Vδ2+TCRγδ+ T lymphocyte subset, expressing the NK receptor protein 1a (NKRP1a; CD161), is expanded in patients with relapsing-remitting multiple sclerosis and uses this molecule to migrate through endothelium. In this work, we show that Vδ1+ and Vδ2+ γδ T lymphocytes use distinct signal transduction pathways to accomplish this function. Indeed, we have found that Vδ1+ cells lack NKRP1a and selectively express the platelet endothelial cell adhesion molecule 1 (PECAM1; CD31), which drives transendothelial migration of this cell subset, at variance with Vδ2+ T cells, which are PECAM1 negative and use NKRP1a for transmigration. Interestingly, when Vδ2+ T cells were pretreated with two specific inhibitors of the calcium calmodulin-dependent kinase II KN62 and KN93, but not with the inactive compound KN92, the number of migrating cells and the rate of transmigration were significantly decreased. In turn, the phosphatidylinositol 3 kinase blockers wortmannin and LY294002 exerted a dose-dependent inhibition of Vδ1+ cell migration. Finally, NKRP1a and PECAM1 engagement led to activation of different signal transduction pathways: indeed, oligomerization of NKRP1a on Vδ2+ T cells activates calcium calmodulin-dependent kinase II, while occupancy of PECAM1 on Vδ1+ cells triggers the phosphatidylinositol 3 kinase-dependent Akt/protein kinase Bα activation. These findings suggest that subsets of γδ T lymphocytes may migrate to the site of lesion in multiple sclerosis using two different signaling pathways to extravasate.
Differentially Regulated Expression and Function of CD22 in Activated B-1 and B-2 Lymphocytes
Authors: Lajaunias Frédéric , Nitschke Lars , Moll Thomas , Martinez-Soria Eduardo , Semac Isabelle , Chicheportiche Yves , Parkhouse R. Michael E. , Izui Shozo 
Published: April 2014

AbstractCD22 is a B cell-restricted transmembrane protein that apparently controls signal transduction thresholds initiated through the B cell Ag receptor (BCR) in response to Ag. However, it is still poorly understood how the expression of CD22 is regulated in B cells after their activation. Here we show that the expression levels of CD22 in conventional B-2 cells are markedly down-regulated after cross-linking of BCR with anti-IgM mAb but are up-regulated after stimulation with LPS, anti-CD40 mAb, or IL-4. In contrast, treatment with anti-IgM mAb barely modulated the expression levels of CD22 in CD5+ B-1 cells, consistent with a weak Ca2+ response in anti-IgM-treated CD5+ B-1 cells. Moreover, in CD22-deficient mice, anti-IgM treatment did not trigger enhanced Ca2+ influx in CD5+ B-1 cells, unlike CD22-deficient splenic B-2 cells, suggesting a relatively limited role of CD22 in BCR signaling in B-1 cells. In contrast, CD22 levels were markedly down-regulated on wild-type B-1 cells in response to LPS or unmethylated CpG-containing oligodeoxynucleotides. These data indicate that the expression and function of CD22 are differentially regulated in B-1 and conventional B-2 cells, which are apparently implicated in innate and adaptive immunity, respectively.
Vaccination with Tumor Peptide in CpG Adjuvant Protects Via IFN-γ-Dependent CD4 Cell Immunity
Authors: Stern Britta V. , Boehm Bernhard O. , Tary-Lehmann Magdalena 
Published: April 2014

AbstractThe low frequency of tumor Ag-specific T cells in vivo has made it challenging to directly measure their clonal sizes and cytokine signatures. We used a new generation ELISPOT approach to study the constitutive immunogenicity of the RMA tumor in syngeneic B6 mice and adjuvant-guided immunity against an MHC class II-restricted RMA peptide, H11.1. The RMA tumor was found to activate cells of the innate immune system and to induce a type 1 polarized, RMA-specific CD4 and CD8 T cell response. With clonal sizes ∼10/106, the magnitude of this constitutively induced immune response did not suffice to control the tumor cell growth. In contrast, immunization with H11.1 peptide, using an immunostimulatory CpG oligonucleotide or CFA as adjuvant, engaged ∼25- or ∼10-fold higher clonal sizes of type 1 polarized CD4 cells, respectively. Therefore, the CpG oligonucleotide functioned as a stronger type 1 adjuvant and, unlike CFA, elicited protective immunity. The protection was IFN-γ dependent, as it was not inducible in IFN-γ knockout mice. Therefore, CpG adjuvant-guided induction of type 1 immunity against tumor Ags might be a promising subunit vaccination approach.
Murine Peyer’s Patches Favor Development of an IL-10-Secreting, Regulatory T Cell Population
Authors: Jump Robin L. , Levine Alan D. 
Published: April 2014

AbstractPeyer’s patches (PP) are believed to be the principal sites for induction of tolerance to Ags from food and commensal flora, yet the phenotype of T cells activated within the PP is largely unexplored. We hypothesize that exposure to Ags within the PP promotes differentiation of T cells with immunoregulatory functions. Cytokine production and cell surface marker expression of murine PP mononuclear cells (MC) are compared with those from mesenteric lymph nodes and peripheral lymph nodes (PLN). In response to stimulation through the TCR/CD3 complex, PP MC exhibit vigorous proliferation, modest production of IL-2, and significantly elevated synthesis of IL-10. Exogenous IL-12 enhances both IL-10 and IFN-γ secretion by activated PP MC. Cell surface marker analysis reveals that PP T cells consist of activated and memory subpopulations compared with the predominantly naive T cells identified in the PLN and mesenteric lymph nodes. Upon stimulation, only CD45RBlowCD4+ PP T cells produce IL-10, whereas secretion of IL-2, IL-4, and IFN-γ was not detected. Furthermore, PP MC, but not PLN MC, stimulated through the TCR/CD3 complex suppress proliferation of purified PLN T cells in vitro, evidence for a regulatory function among PP lymphocytes. We conclude that PP favor differentiation of an IL-10-producing, regulatory CD45RBlowCD4+ T cell population and that inhibition of T cell proliferation by activated PP MC may reflect regulatory activity consistent with T regulatory cells.
Catecholamines Inhibit the Antigen-Presenting Capability of Epidermal Langerhans Cells
Authors: Seiffert Kristina , Hosoi Junichi , Torii Hideshi , Ozawa Hiroaki , Ding Wanhong , Campton Kristina , Wagner John A. , Granstein Richard D. 
Published: April 2014

AbstractThe sympathetic nervous system modulates immune function at a number of levels. Within the epidermis, APCs (Langerhans cells (LC)) are frequently anatomically associated with peripheral nerves. Furthermore, some neuropeptides have been shown to regulate LC Ag-presenting function. We explored the expression of adrenergic receptors (AR) in murine LC and assessed their functional role on Ag presentation and modulation of cutaneous immune responses. Both purified LC and the LC-like cell lines XS52-4D and XS106 expressed mRNA for the ARs α1A and β2. XS106 cells and purified LC also expressed β1-AR mRNA. Treatment of murine epidermal cell preparations with epinephrine (EPI) or norepinephrine inhibited Ag presentation in vitro. Furthermore, pretreatment of epidermal cells with EPI or norepinephrine in vitro suppressed the ability of these cells to present Ag for elicitation of delayed-type hypersensitivity in previously immunized mice. This effect was blocked by use of the β2-adrenergic antagonist ICI 118,551 but not by the α-antagonist phentolamine. Local intradermal injection of EPI inhibited the induction of contact hypersensitivity to epicutaneously administered haptens. Surprisingly, injection of EPI at a distant site also suppressed induction of contact hypersensitivity. Thus, catecholamines may have both local and systemic effects. We conclude that specific ARs are expressed on LC and that signaling through these receptors can decrease epidermal immune reactions.
The Absence of Itk Inhibits Positive Selection Without Changing Lineage Commitment
Authors: Lucas Julie A. , Atherly Luana O. , Berg Leslie J. 
Published: April 2014

AbstractThe Tec family tyrosine kinase Itk is critical for efficient signaling downstream of the TCR. Biochemically, Itk is directly phosphorylated and activated by Lck. Subsequently, Itk activates phospholipase C-γ1, leading to calcium mobilization and extracellular signal-regulated kinase/mitogen-activated protein kinase activation. These observations suggested that Itk might play an important role in positive selection and CD4/CD8 lineage commitment during T cell development in the thymus. To test this, we crossed Itk-deficient mice to three lines of TCR transgenics and analyzed progeny on three different MHC backgrounds. Analysis of these mice revealed that fewer TCR transgenic T cells develop in the absence of Itk. In addition, examination of multiple T cell development markers indicates that multiple stages of positive selection are affected by the absence of Itk, but the T cells that do develop appear normal. In contrast to the defects in positive selection, CD4/CD8 lineage commitment seems to be intact in all the TCR transgenic itk−/− lines tested. Overall, these data indicate that altering TCR signals by the removal of Itk does not affect the appropriate differentiation of thymocytes based on their MHC specificity, but does impact the efficiency with which thymocytes complete their maturation process.
Down-Regulation of Monocyte Apoptosis by Phagocytosis of Platelets: Involvement of a Caspase-9, Caspase-3, and Heat Shock Protein 70-Dependent Pathway
Authors: Lang Detlef , Dohle Frank , Terstesse Martin , Bangen Philip , August Christian , Pauels Hans-Gerd , Heidenreich Stefan 
Published: April 2014

AbstractMonocytes interact and cross-talk with platelets in many settings including inflammation, hemostasis, or vascular disorders. During inflammatory diseases, there is a rapid targeting of monocytes and platelets to points of inflammation and endothelial injury, where they lie side-by-side. In this in vitro study, we investigated different interactions between monocytes and platelets and elucidated whether platelets might affect monocyte apoptosis. Freshly isolated human monocytes were rendered apoptotic by serum deprivation or CD95 ligation and cocultured with platelets. Monocyte apoptosis was determined by flow cytometry, TUNEL staining, DNA electrophoresis, and transmission electron microscopy imaging. We could show that monocyte apoptosis was highly suppressed when platelets were added to the cultures. Transmission electron microscopy depicted that monocytes completely ingested thrombocytes by phagocytosis. Blocking thrombocyte uptake by the phagocytosis inhibitor cytochalasin D abrogated the enhanced monocyte survival and led to high apoptosis levels. Monocyte survival was paralleled by down-regulation of caspase-9 and -3 and up-regulation of heat shock protein 70 during uptake of platelets. Platelet supernatants and contents of platelet granules were ineffective in altering monocyte senescence. Also, ingestion of latex beads or zymosan by monocytes was ineffective to mimic platelet-dependent rescue from apoptosis. In conclusion, this study shows that platelets can suppress apoptosis of monocytes by a specific phagocytosis-dependent process with further consequences for atherosclerotic or inflammatory conditions.
Regulation of Diabetes Development by Regulatory T Cells in Pancreatic Islet Antigen-Specific TCR Transgenic Nonobese Diabetic Mice
Authors: Kanagawa Osami , Militech Ana , Vaupel Barbala A. 
Published: April 2014

AbstractNonobese diabetic (NOD) mice carrying a transgenic TCR from an islet Ag-specific CD4 T cell clone, BDC2.5, do not develop diabetes. In contrast, the same transgenic NOD mice on the SCID background develop diabetes within 4 wk after birth. Using a newly developed mAb specific for the BDC2.5 TCR, we examined the interaction between diabetogenic T cells and regulatory T cells in NOD.BDC transgenic mice. CD4 T cells from NOD.BDC mice, expressing high levels of the clonotype, transfer diabetes to NOD.SCID recipients. In contrast, CD4 T cells expressing low levels due to the expression of both transgenic and endogenous TCR α-chains inhibit diabetes transfer. The clonotype-low CD4 T cells appear late in the ontogeny in the thymus and peripheral lymphoid organs, coinciding with resistance to cyclophosphamide-induced diabetes. These results demonstrate that diabetic processes in NOD.BDC mice are regulated by a balance between diabetogenic T cells and regulatory T cells. In the absence of specific manipulation, regulatory T cell function seems to be dominant and mice remain diabetes free. Understanding of mechanisms by which regulatory T cells inhibit diabetogenic processes would provide means to prevent diabetes development in high-risk human populations.