Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells.
AuthorsLonghi MP, Wright K, Lauder SN, Nowell MA, Jones GW, Godkin AJ, Jones SA, Gallimore AM,
JournalPLoS Pathog
PubMed ID18389078
'Currently, our understanding of mechanisms underlying cell-mediated immunity and particularly of mechanisms that promote robust T cell memory to respiratory viruses is incomplete. Interleukin (IL)-6 has recently re-emerged as an important regulator of T cell proliferation and survival. Since IL-6 is abundant following infection with influenza virus, we analyzed virus-specific ... More
Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission.
AuthorsDagda RK, Cherra SJ, Kulich SM, Tandon A, Park D, Chu CT,
JournalJ Biol Chem
PubMed ID19279012
'Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy ... More
IFN-gamma gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice.
AuthorsDierksheide JE, Baiocchi RA, Ferketich AK, Roychowdhury S, Pelletier RP, Eisenbeis CF, Caligiuri MA, VanBuskirk AM
JournalBlood
PubMed ID15498860
'Posttransplantation lymphoproliferative disorder (PTLD) is a devastating post-transplantation complication often associated with Epstein-Barr virus (EBV). Although the type and length of immunosuppression are risk factors, a patient''s inherent immune capacity also likely contributes to this disorder. This report uses severe-combined immunodeficient mice given injections of human peripheral blood leukocytes (hu ... More
A biochemical and functional characterization of diet-induced brain insulin resistance.
AuthorsMielke JG, Taghibiglou C, Liu L, Zhang Y, Jia Z, Adeli K, Wang YT
JournalJ Neurochem
PubMed ID15935073
'While considerable research has examined diminished insulin responses within peripheral tissues, comparatively little has been done to examine the effects of this metabolic disruption upon the CNS. The present study employed biochemical and electrophysiological assays of acutely prepared brain slices to determine whether neural insulin resistance is a component of ... More
Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion.
AuthorsLibura J, Slater DJ, Felix CA, Richardson C
JournalBlood
PubMed ID15528316
'Rearrangements involving the MLL gene on chromosome band 11q23 are a hallmark of therapy-related acute myeloid leukemias following treatment with topoisomerase II poisons including etoposide. Therapy-related and de novo genomic translocation breakpoints cluster within a well-characterized 8.3-kb fragment of MLL. Repair of etoposide-stabilized DNA topoisomerase II covalent complexes may initiate ... More
The effects of 2-methoxyoestrogen sulphamates on the in vitro and in vivo proliferation of breast cancer cells.
AuthorsUtsumi T, Leese MP, Chander SK, Gaukroger K, Purohit A, Newman SP, Potter BV, Reed MJ
JournalJ Steroid Biochem Mol Biol
PubMed ID15862969
'2-Methoxyoestrogen sulphamates are a new class of compounds, which inhibit breast cancer cell proliferation and are also potent inhibitors of steroid sulphatase (STS) activity. In the present study, we have used two cell proliferation assays (MTS and AB) to identify potent new compounds in this class. Similar IC(50) values were ... More
A positive regulatory role for suppressor of cytokine signaling 1 in IFN-gamma-induced MHC class II expression in fibroblasts.
AuthorsIlangumaran S, Finan D, La Rose J, Raine J, Silverstein A, De Sepulveda P, Rottapel R
JournalJ Immunol
PubMed ID12391216
'Suppressor of cytokine signaling 1 (SOCS1) is rapidly induced following stimulation by several cytokines. SOCS1 negatively regulates cytokine receptor signal transduction by inhibiting Janus family tyrosine kinases. Lack of such feedback regulation underlies the premature death of SOCS1(-/-) mice due to unbridled IFN-gamma signaling. We used mouse embryo fibroblasts derived ... More
Evaluation of the efficacy of disinfection procedures against Burkholderia cenocepacia biofilms.
AuthorsPeeters E, Nelis HJ, Coenye T
JournalJ Hosp Infect
PubMed ID18977555
'SUMMARY: In the present study we evaluated the efficacy of various procedures recommended for the disinfection of respiratory equipment and other materials in cystic fibrosis, using both planktonic and sessile Burkholderia cenocepacia cells. A modified European Suspension Test was performed to determine the effects of the disinfection procedures on planktonic ... More
Characterization of chemically induced hepatotoxicity in collagen sandwiches of rat hepatocytes.
AuthorsFarkas D, Tannenbaum SR
JournalToxicol Sci
PubMed ID15772367
'It has been shown that hepatocytes cultured in a collagen sandwich configuration maintain cell viability, morphology, and drug metabolizing activities for several weeks. The purpose of this study was to characterize chemically induced general toxicity in this system by exposing hepatocytes to eight different hepatotoxic compounds. Cell function and viability ... More
Lysophosphatidic acid acyltransferase-beta is a prognostic marker and therapeutic target in gynecologic malignancies.
AuthorsSpringett GM, Bonham L, Hummer A, Linkov I, Misra D, Ma C, Pezzoni G, Di Giovine S, Singer J, Kawasaki H, Spriggs D, Soslow R, Dupont J
JournalCancer Res
PubMed ID16230405
'Lysophosphatidic acid, the substrate for lysophosphatidic acid acyltransferase beta (LPAAT-beta), is a well-studied autocrine/paracrine signaling molecule that is secreted by ovarian cancer cells and is found at elevated levels in the blood and ascites fluid of women with ovarian cancer. LPAAT-beta converts lysophosphatidic acid to phosphatidic acid, which functions as ... More
A new Alamar Blue viability assay to rapidly quantify oligodendrocyte death.
AuthorsBack SA, Khan R, Gan X, Rosenberg PA, Volpe JJ
JournalJ Neurosci Methods
PubMed ID10522823
'We developed a rapid fluorometric viability assay for primary cultures of OL precursors (preOLs) or mature OLs that utilized the oxidation/reduction indicator dye Alamar Blue (AB). PreOLs had a lower rate of AB reduction than did mature OLs (0.02 +/- 0.01 units/min per cell versus 0.07 +/- 0.01). The assay ... More
Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation.
AuthorsLewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, Sherman DR
JournalJ Infect Dis
PubMed ID12508154
'The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The ... More
Development of colorimetric microtiter plate assay for assessment of antimicrobials against Acanthamoeba.
AuthorsMcBride J, Ingram PR, Henriquez FL, Roberts CW
JournalJ Clin Microbiol
PubMed ID15695656
'We have developed and optimized a 96-well microtiter plate assay, based on the reduction of alamarBlue, to assess the efficacies of much needed new antimicrobials against Acanthamoeba species. This assay has been optimized for determination of drug efficacy against two potentially pathogenic species, Acanthamoeba castellanii and Acanthamoeba polyphaga, and has ... More
Dysregulated ryanodine receptors mediate cellular toxicity: restoration of normal phenotype by FKBP12.6.
AuthorsGeorge CH, Higgs GV, Mackrill JJ, Lai FA
JournalJ Biol Chem
PubMed ID12754204
'Ca2+ homeostasis is a vital cellular control mechanism in which Ca2+ release from intracellular stores plays a central role. Ryanodine receptor (RyR)-mediated Ca2+ release is a key modulator of Ca2+ homeostasis, and the defective regulation of RyR is pathogenic. However, the molecular events underlying RyR-mediated pathology remain undefined. Cells stably ... More
Tetracyclines convert the osteoclastic-differentiation pathway of progenitor cells to produce dendritic cell-like cells.
AuthorsKinugawa S, Koide M, Kobayashi Y, Mizoguchi T, Ninomiya T, Muto A, Kawahara I, Nakamura M, Yasuda H, Takahashi N, Udagawa N
JournalJ Immunol
PubMed ID22250082
'Tetracyclines, such as doxycycline and minocycline, are used to suppress the growth of bacteria in patients with inflammatory diseases. Tetracyclines have been shown to prevent bone loss, but the mechanism involved is unknown. Osteoclasts and dendritic cells (DCs) are derived from common progenitors, such as bone marrow-derived macrophages (BMMs). In ... More
A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction.
AuthorsZemans RL, Briones N, Young SK, Malcolm KC, Refaeli Y, Downey GP, Worthen GS,
JournalJ Immunol Methods
PubMed ID19010330
'Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved ... More
TDAG51 is an ERK signaling target that opposes ERK-mediated HME16C mammary epithelial cell transformation.
AuthorsOberst MD, Beberman SJ, Zhao L, Yin JJ, Ward Y, Kelly K,
JournalBMC Cancer
PubMed ID18597688
'INTRODUCTION: Signaling downstream of Ras is mediated by three major pathways, Raf/ERK, phosphatidylinositol 3 kinase (PI3K), and Ral guanine nucleotide exchange factor (RalGEF). Ras signal transduction pathways play an important role in breast cancer progression, as evidenced by the frequent over-expression of the Ras-activating epidermal growth factor receptors EGFR and ... More
Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line.
AuthorsBopp SK, Lettieri T,
JournalBMC Pharmacol
PubMed ID18513395
'BACKGROUND: A broad spectrum of cytotoxicity assays is currently used in the fields of (eco)toxicology and pharmacology. To choose an appropriate assay, different parameters like test compounds, detection mechanism, specificity, and sensitivity have to be considered. Furthermore, tissue or cell line can influence test performance. For zebrafish (Danio rerio), as ... More
GSK-3ß regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1a.
AuthorsFlügel D, Görlach A, Kietzmann T
JournalBlood
PubMed ID22144179
'The hypoxia-inducible transcription factor-1a (HIF-1a) is a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions. Therefore, the identification of critical players regulating HIF-1a is not only important for the understanding of angiogenesis and different cancer phenotypes, but also for unraveling new therapeutic options. ... More
The challenge to measure cell proliferation in two and three dimensions.
AuthorsNg KW, Leong DT, Hutmacher DW
JournalTissue Eng
PubMed ID15738673
'Various assays, using different strategies, are available for assessing cultured cell proliferation. These include measurement of metabolic activity (tetrazolium salts and alamarBlue), DNA quantification using fluorophores (Hoechst 33258 and PicoGreen), uptake of radioactively-labeled DNA precursors such as [3H]thymidine, and physical counting (hemocytometer). These assays are well established in characterizing cell ... More
Cytotoxic effects of 110 reference compounds on HepG2 cells and for 60 compounds on HeLa, ECC-1 and CHO cells. II mechanistic assays on NAD(P)H, ATP and DNA contents.
AuthorsSchoonen WG, de Roos JA, Westerink WM, Débiton E,
JournalToxicol In Vitro
PubMed ID15826807
'In this study the focus is on the comparison of fluorometric assays, using Alamar Blue (AB) and Hoechst 33342 coloration, and luminometric assays, using Cyto-Lite and ATP-Lite, for toxicity measurements. With AB, ATP-Lite and Cyto-Lite the energy status of the cell is measured and with Hoechst 33342 the amount of ... More
Expression of G protein-coupled receptor 19 in human lung cancer cells is triggered by entry into S-phase and supports G(2)-M cell-cycle progression.
'It has long been known that G protein-coupled receptors (GPCR) are subject to illegitimate expression in tumor cells. Presumably, hijacking the normal physiologic functions of GPCRs contributes to all biologic capabilities acquired during tumorigenesis. Here, we searched for GPCRs that were expressed in lung cancer: the mRNA encoding orphan G ... More
EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion.
AuthorsNakada M, Niska JA, Tran NL, McDonough WS, Berens ME
JournalAm J Pathol
PubMed ID16049340
'Eph receptor tyrosine kinases mediate neurodevelopmental processes such as boundary formation, vasculogenesis, and cell migration. Recently, we found that overexpression of EphB2 in glioma cells results in reduced cell adhesion and increased cell invasion. Since R-Ras has been shown to play a critical role in EphB2 regulation of integrin activity, ... More
Phototoxic effects of 635-nm light on canine transitional cell carcinoma cells incubated with 5-aminolevulinic acid.
AuthorsRidgway TD, Lucroy MD
JournalAm J Vet Res
PubMed ID12602579
'To determine whether transitional cell carcinoma (TCC) cells incubated in media containing 5-aminolevulinic acid (ALA) would produce sufficient protoporphyrin IX (PpIX) to cause lethal phototoxic effects when exposed to 635-nm light.' ... More
Augmentation of the bactericidal activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by amino acid substitutions.
AuthorsNagaoka I, Kuwahara-Arai K, Tamura H, Hiramatsu K, Hirata M
JournalInflamm Res
PubMed ID15750713
'Mammalian myeloid and epithelial cells express various peptide antibiotics (such as defensins and cathelicidins) that contribute to the innate host defense against invading micro-organisms. Among these, human cathelicidin CAP18/LL-37 (L1-S37) possesses potent antibacterial activities against Gram-positive and Gram-negative bacteria. In this study, to develop peptide derivatives with improved bactericidal actions, ... More
Connexin mediates gap junction-independent resistance to cellular injury.
AuthorsLin JH, Yang J, Liu S, Takano T, Wang X, Gao Q, Willecke K, Nedergaard M
JournalJ Neurosci
PubMed ID12533603
'Although gap junctions regulate essential processes during development and differentiation, the role of gap junctions in cell death is poorly understood. We demonstrate here that the forced expression of connexin 43 (Cx43), the main constituent of astrocytic gap junctions, protected against cell injury with a potency that was comparable with ... More
Comparison of alamar blue and MTT assays for high through-put screening.
AuthorsHamid R, Rotshteyn Y, Rabadi L, Parikh R, Bullock P
JournalToxicol In Vitro
PubMed ID15251189
'The performance of alamar blue and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell viability assays in a high through-put format were compared. A total of 117 drugs chosen for their wide range of therapeutic areas were screened at 10 microM using both assays in human hepatoma cell line HepG2. Except for terfenadine ... More
Inhibition of tyrosine kinases blocks adhesion-induced T-cell coactivation without interfering with T-cell adhesion to endothelial cell-surface ligands.
AuthorsNowlin DM, Cardarelli PM, Young L, Mah J, Felts KA, Mastrangelo M, Cobb RR
JournalInflammation
PubMed ID11936754
'Integrin and cell adhesion molecule-regulated cellular adhesion plays an integral part in the recruitment and activation of lymphocytes. T-cell activation is a dynamic process subject to integrin-dependent and -independent regulation. Stimulation of human peripheral blood T cells by the anti-CD3 monoclonal antibody results in a rapid upregulation of integrin affinity. ... More
The Leishmania donovani UMP synthase is essential for promastigote viability and has an unusual tetrameric structure that exhibits substrate-controlled oligomerization.
AuthorsFrench JB, Yates PA, Soysa DR, Boitz JM, Carter NS, Chang B, Ullman B, Ealick SE
JournalJ Biol Chem
PubMed ID21507942
'The final two steps of de novo uridine 5''-monophosphate (UMP) biosynthesis are catalyzed by orotate phosphoribosyltransferase (OPRT) and orotidine 5''-monophosphate decarboxylase (OMPDC). In most prokaryotes and simple eukaryotes these two enzymes are encoded by separate genes, whereas in mammals they are expressed as a bifunctional gene product called UMP synthase ... More
Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment.
'We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of ... More
Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance.
AuthorsMacKeigan JP, Murphy LO, Blenis J
JournalNat Cell Biol
PubMed ID15864305
'Evasion from apoptosis is a hallmark of cancer, and recent success using targeted therapeutics underscores the importance of identifying anti-apoptotic survival pathways. Here we utilize RNA interference (RNAi) to systematically screen the kinase and phosphatase component of the human genome. In addition to known kinases, we identified several new survival ... More
The cross-linked biopolymer hyaluronic acid as an artificial vitreous substitute.
AuthorsSchramm C, Spitzer MS, Henke-Fahle S, Steinmetz G, Januschowski K, Heiduschka P, Geis-Gerstorfer J, Biedermann T, Bartz-Schmidt KU, Szurman P
JournalInvest Ophthalmol Vis Sci
PubMed ID22199245
Biopolymers are promising substances in the development of a new vitreous substitute to overcome the drawbacks associated with current hydrophobic tamponade materials.
Chemosensitization of carmustine with maitake beta-glucan on androgen-independent prostatic cancer cells: involvement of glyoxalase I.
To improve the poor efficacy (< 10%) of chemotherapy for patients with hormone-refractory prostate cancer, we investigated a possible cytotoxic effect of carmustine/beta-glucan combination on prostatic cancer PC-3 cells, focusing on a glutathione-dependent detoxifying enzyme, glyoxalase I (Gly-I). ... More
Effects of secreted frizzled-related protein 3 on osteoblasts in vitro.
AuthorsChung YS, Baylink DJ, Srivastava AK, Amaar Y, Tapia B, Kasukawa Y, Mohan S
JournalJ Bone Miner Res
PubMed ID15312239
To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation. We found that sFRP3 unexpectedly increased osteoblast differentiation, suggesting it may act through other mechanisms besides acting as a decoy receptor for Wnt's. ... More
Resistance of planktonic and biofilm-grown Burkholderia cepacia complex isolates to the transition metal gallium.
AuthorsPeeters E, Nelis HJ, Coenye T
JournalJ Antimicrob Chemother
PubMed ID18310047
The Burkholderia cepacia complex is a group of pathogens that can cause severe pulmonary infections in cystic fibrosis (CF) patients. The aim of the present study was to investigate the in vitro activity of gallium against planktonic and biofilm-grown B. cepacia complex isolates. ... More
Identification of bis-quindolines as new antiinfective agents.
AuthorsMardenborough LG, Zhu XY, Fan P, Jacob MR, Khan SI, Walker LA, Ablordeppey SY
JournalBioorg Med Chem
PubMed ID15911310
Several N-substituted quindolines were made to further evaluate the role of N-alkylation on the activity of indoloquinolines as antifungal agents. While N-5 substitution is required for these activities, N-10 alkylation alone leads to inactive products but is tolerated in the presence of N-5 alkyl groups. It was also discovered that ... More
Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis.
New classes of drugs are needed to treat tuberculosis (TB) in order to combat the emergence of resistance to existing agents and shorten the duration of therapy. Targeting DNA gyrase is a clinically validated therapeutic approach using fluoroquinolone antibiotics to target the gyrase subunit A (GyrA) of the heterotetramer. Increasing ... More
Assessment of neuronal viability with Alamar blue in cortical and granule cell cultures.
AuthorsWhite MJ, DiCaprio MJ, Greenberg DA
JournalJ Neurosci Methods
PubMed ID9007759
Alamar blue, a redox indicator of cell viability in nonneuronal systems, was used to assess neuronal viability in cultures prepared from embryonic rat cerebral cortex and neonatal rat cerebellum. Alamar blue fluorescence varied linearly with cell number and was decreased by treating cortical or cerebellar granule cell cultures with excitatory ... More
A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue.
AuthorsTanaka TQ, Williamson KC,
JournalMol Biochem Parasitol
PubMed ID21316401
Efforts to move from malaria control to eradication will require new approaches to block malaria transmission, such as the development of anti-malarial drugs with gametocytocidal activity. Here fluorescent oxidoreduction indicator alamarBlue is used to develop a screen for gametocyte viability. The fluorescent signal increases linearly with gametocyte number (R(2)=0.99) and ... More
The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action.
AuthorsSmith DE, Hanna R, Della Friend Moore H, Chen H, Farese AM, MacVittie TJ, Virca GD, Sims JE
JournalImmunity
PubMed ID12530978
Regulation of the activity of the proinflammatory cytokine IL-1 is complex, involving transcriptional and translational control, precursor processing, a receptor antagonist (IL-1ra), and a decoy receptor. Here we report that the soluble form of the IL-1 receptor accessory protein (AcP) increases the affinity of binding of human IL-1alpha and IL-1beta ... More
Paper-supported 3D cell culture for tissue-based bioassays.
AuthorsDerda R, Laromaine A, Mammoto A, Tang SK, Mammoto T, Ingber DE, Whitesides GM,
JournalProc Natl Acad Sci U S A
PubMed ID19846768
Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. ... More
Inactivation of lactate dehydrogenase by several chemicals: implications for in vitro toxicology studies.
AuthorsKendig DM, Tarloff JB,
JournalToxicol In Vitro
PubMed ID17079110
Lactate dehydrogenase (LDH) release is frequently used as an end-point for cytotoxicity studies. We have been unable to measure LDH release during studies using para-aminophenol (PAP) in LLC-PK(1) cells. When LLC-PK(1) cells were incubated with either PAP (0-10 mM) or menadione (0-1000 microM), viability was markedly reduced when assessed by ... More
Design of the artificial acellular feeder layer for the efficient propagation of mouse embryonic stem cells.
AuthorsNagaoka M, Hagiwara Y, Takemura K, Murakami Y, Li J, Duncan SA, Akaike T,
JournalJ Biol Chem
PubMed ID18614540
Embryonic stem (ES) cells are pluripotent-undifferentiated cells that have a great interest for the investigation of developmental biology. Murine ES cells maintain their pluripotency by the supplementation of the leukemia inhibitory factor (LIF). LIF is reported to act as a matrix-anchored form, and immobilized cytokines are useful to sustain their ... More
A single amino acid difference between human and monkey interleukin (IL)-1beta dictates effective binding to soluble type II IL-1 receptor.
AuthorsSmith DE, Ketchem RR, Moore H, Anderson Z, Renshaw BR, Friend DJ, Sims JE
JournalJ Biol Chem
PubMed ID12356774
Soluble type II interleukin (IL)-1 receptor (sIL1R-II) binds human IL-1beta with high affinity and neutralizes its activity. Recombinant sIL1R-II is considered a potentially useful anti-IL-1 therapeutic, and preclinical studies have been undertaken with this molecule in primates. To better understand the cytokine-receptor interactions occurring in this nonhuman context, monkey IL-1 ... More
Tumors can evade immune responses through suppressor signals that dysregulate host effector cell function. In this study we demonstrate that tumor-derived suppressor molecules impede host antitumor immune activity through dysregulation of multiple macrophage (Mphi) pathways, including suppressed production of cytotoxic and immunostimulatory agents and impaired expression of the interferon regulatory ... More
Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects.
AuthorsXu WS, Perez G, Ngo L, Gui CY, Marks PA
JournalCancer Res
PubMed ID16140952
Histone deacetylase (HDAC) inhibitors can induce various transformed cells to undergo growth arrest and/or death. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor which is in phase I/II clinical trials and has shown antitumor activity in hematologic and solid tumors at doses well tolerated by patients. HDAC is the target ... More
Immunosuppression in specific-pathogen-free broilers administered infectious bursal disease virus vaccines by in ovo route.
AuthorsCorley MM, Giambrone JJ
JournalAvian Dis
PubMed ID12495040
The effect of two infectious bursal disease virus (IBDV) vaccines (IBDV-immune complex [Icx] and IBDV-2512), administered in ovo, on the cell-mediated immunity of specific-pathogen-free (SPF) broilers was examined. A decrease (P < 0.05) in the T-cell mitogenic response occurred in birds vaccinated with both vaccines on days 9 and 21 ... More
Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro.
AuthorsWyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA
JournalAntiviral Res
PubMed ID14516921
Human metapneumovirus (hMPV) is a newly recognized pathogen that like its better-known relative, human respiratory syncytial virus (hRSV), appears to be ubiquitous and an important cause of respiratory disease in diverse subpopulations. No antivirals or vaccines are currently approved for the treatment or prevention of hMPV infections. However, ribavirin is ... More
Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide, a new antiviral strategy for influenza virus.
AuthorsLee KK, Pessi A, Gui L, Santoprete A, Talekar A, Moscona A, Porotto M
JournalJ Biol Chem
PubMed ID21994935
We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol conjugation and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside of intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose ... More
MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression, invasion and intrinsic tumorigenicity of melanoma cells.
AuthorsGarrido C, Paco L, Romero I, Berruguilla E, Stefansky J, Collado A, Algarra I, Garrido F, Garcia-Lora AM
JournalCarcinogenesis
PubMed ID22219178
The alteration of MHC class I (MHC-I) expression is a frequent event during cancer progression, allowing tumor cells to evade the immune system. We report that the loss of one major histocompatibility complex haplotype in human melanoma cells not only allowed them to evade immunosurveillance but also increased their intrinsic ... More
Early gene response in lithium chloride induced apoptosis.
AuthorsZhang WV, Jüllig M, Connolly AR, Stott NS
JournalApoptosis
PubMed ID15711924
Depending on the cellular context, lithium chloride can lead to enhanced proliferation, cell cycle arrest or apoptosis in mammalian cells. Although substantial work has been made to elucidate the downstream events in the case of lithium chloride-induced cellular proliferation, the molecular response to lithium chloride treatment in the apoptotic scenario ... More
Modulation of JB6 mouse epidermal cell transformation response by the prostaglandin F2alpha receptor.
Prostaglandin F(2alpha) (PGF(2alpha)) modulates clonal selection processes in the mouse skin model of carcinogenesis. In this study we investigated whether JB6 mouse epidermal cells expressed a functional PGF(2alpha) receptor (FP) coupled with a cell-transformation response. Treatment of JB6 cells with an FP agonist (fluprostenol) potently (pM-nM) increased anchorage-dependent and anchorage-independent ... More
Functional differences among FimA variants of Porphyromonas gingivalis and their effects on adhesion to and invasion of human epithelial cells.
AuthorsNakagawa I, Amano A, Kuboniwa M, Nakamura T, Kawabata S, Hamada S
JournalInfect Immun
PubMed ID11748193
Fimbriae of Porphyromonas gingivalis, a periodontopathogen, play an important role in its adhesion to and invasion of host cells. The fimA genes encoding fimbrillin (FimA), a subunit protein of fimbriae, have been classified into five types, types I to V, based on nucleotide sequences. We previously reported that P. gingivalis ... More
In vivo efficacy of glycopeptide-colistin combination therapies in a Galleria mellonella model of Acinetobacter baumannii infection.
AuthorsHornsey M, Wareham DW
JournalAntimicrob Agents Chemother
PubMed ID21502628
The treatment of Acinetobacter baumannii infections poses a significant clinical challenge, with isolates resistant to all commonly used agents increasingly being reported. With few new agents in the pipeline, clinicians are increasingly turning to combinations of antimicrobials in the hope that they may act synergistically together. In this study we ... More
In vitro and in vivo antifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistant Candida albicans.
To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs. A preliminary in vitro study showed ... More
The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells.
AuthorsDjordjevic T, Pogrebniak A, BelAiba RS, Bonello S, Wotzlaw C, Acker H, Hess J, Görlach A
JournalFree Radic Biol Med
PubMed ID15683718
Endothelial dysfunction is characterized by increased levels of reactive oxygen species (ROS) and a prothrombotic state. The mechanisms linking thrombosis to ROS production in the endothelium are not well understood. We investigated the role of thrombin in regulating NADPH oxidase-dependent ROS production and expression of its subunit p22phox in the ... More
Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity.
AuthorsMalinin NL, Wright S, Seubert P, Schenk D, Griswold-Prenner I
JournalProc Natl Acad Sci U S A
PubMed ID15710903
Based on a variety of genetic, biochemical, and neuropathological evidence, amyloid-beta peptide (Abeta) has been suggested to be causal in Alzheimer's disease (AD). Abeta has been shown to mediate neurodegenerative and inflammatory changes associated with amyloid plaques, as well as exert direct neurotoxicity through oligomeric forms of Abeta. The mechanism ... More
TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle.
AuthorsPera T, Sami R, Zaagsma J, Meurs H
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID21873447
Increased airway smooth muscle (ASM) mass is a major feature of airway remodeling in asthma and chronic obstructive pulmonary disease. Growth factors induce a proliferative ASM phenotype, characterized by an increased proliferative state and a decreased contractile protein expression, reducing contractility of the muscle. Transforming growth factor-ß-activated kinase 1 (TAK1), ... More
The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine-induced neurotoxicity.
AuthorsNoelker C, Bacher M, Gocke P, Wei X, Klockgether T, Du Y, Dodel R
JournalNeurosci Lett
PubMed ID15894425
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons of the substantia nigra pars compacta. 6-Hydroxydopamine (6-OHDA) is specific to dopaminergic neurons in intrastriatal rodent models. It induces neuronal death either via uncoupling mitochondrial oxidative phosphorylation resulting in energy deprivation or alternatively, is associated ... More
Toxic potential of five freshwater Phormidium species (Cyanoprokaryota).
AuthorsTeneva I, Dzhambazov B, Koleva L, Mladenov R, Schirmer K
JournalToxicon
PubMed ID15804520
Among the Cyanoprokaryota (blue-green algae), the genus Phormidium has thus far rarely been studied with respect to toxin production and potentially resulting human and environmental health effects. We here show that five previously unexplored freshwater species of this genus (Ph. bijugatum, Ph. molle, Ph. papyraceum, Ph. uncinatum, Ph. autumnale) are ... More
The cytochrome c maturation locus of Legionella pneumophila promotes iron assimilation and intracellular infection and contains a strain-specific insertion sequence element.
Previously, we obtained a Legionella pneumophila mutant, NU208, that is hypersensitive to iron chelators when grown on standard Legionella media. Here, we demonstrate that NU208 is also impaired for growth in media that simply lack their iron supplement. The mutant was not, however, impaired for the production of legiobactin, the ... More
Macrophage effector functions controlled by Bruton's tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance.
AuthorsMukhopadhyay S, Mohanty M, Mangla A, George A, Bal V, Rath S, Ravindran B
JournalJ Immunol
PubMed ID11884462
Macrophages from X-linked immunodeficient (xid) mice lacking functional Bruton's tyrosine kinase (Btk) show poor NO induction and enhanced IL-12 induction, and contribute to delayed clearance of injected microfilaria (mf) in vivo. We now show that Btk is involved in other macrophage effector functions, such as bactericidal activity and secretion of ... More
Febrile-range hyperthermia augments lipopolysaccharide-induced lung injury by a mechanism of enhanced alveolar epithelial apoptosis.
AuthorsLipke AB, Matute-Bello G, Herrero R, Kurahashi K, Wong VA, Mongovin SM, Martin TR
JournalJ Immunol
PubMed ID20200273
Fever is common in critically ill patients and is associated with worse clinical outcomes, including increased intensive care unit mortality. In animal models, febrile-range hyperthermia (FRH) worsens acute lung injury, but the mechanisms by which this occurs remain uncertain. We hypothesized that FRH augments the response of the alveolar epithelium ... More
A novel cell-associated protection assay demonstrates the ability of certain antibiotics to protect ocular surface cell lines from subsequent clinical Staphylococcus aureus challenge.
AuthorsWingard JB, Romanowski EG, Kowalski RP, Mah FS, Ling Y, Bilonick RA, Shanks RM
JournalAntimicrob Agents Chemother
PubMed ID21628536
In vivo effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new in vitro method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline ... More