tbuckley/cabot-search huggingface dataset:
764. Attenuation of Treg Cells by GITR Ligand Led to Synergistic Enhancement of Treatment Efficacy with Immune-Stimulatory Therapies in Mice Bearing Metastatic 4T1 Breast Carcinoma
Authors: Li Chen, Tian-gui Huang, Marcia Meseck, Savio L.C. Woo
Journal: Molecular Therapy (2006)

CD25+CD4+ regulatory T cells (Treg) are capable of suppressing cytolytic activity of CD8+ T cells which may hamper the development of effective immune therapies against cancer. The glucocorticoid-induced TNF receptor family-related gene (GITR) is a membrane receptor is predominantly expressed on these Treg cells, and the immune-suppressive activity of Treg can be inhibited by its interaction with GITR Ligand (GITRL) expressed on antigen presenting cells. Depletion of Treg using anti-CD25 or blocking GITR signaling by GITRL alone, however, was not capable of eradicating pre-established tumors in laboratory animals. Implantation of poorly immunogenic but highly tumorigenic 4T1 breast carcinoma cells in the mammary glands of syngeneic Balb/c mice led to the development of orthotopic lesions that are spontaneously metastatic. We showed that an immune enhancement therapy by intratumoral delivery of a recombinant adenovirus vector expressing murine GMCSF and IL12 (Ad.mGMCSF-IRES-mIL12), in combination with intraperitoneal administration of a fusion protein of murine immunoglobulin with the ecto-domain of murine 4-1BB ligand (mIg-m4-1BBLs), in mice bearing 4T1 breast carcinoma led to significantly prolonged survival, although the treated animals eventually succumbed to tumor relapse. The Treg population was significantly elevated in the splenocytes of the treated animals and depletion of CD4+CD25+ cell population led to a significant increase in splenic T cell proliferation activity in vitro. We hypothesized that addition of a fusion protein made of murine immunoglobulin and the ecto-domain of GITR ligand (mIg-mGITRLs) to the treatment regimen would have a synergistic effect on anti-tumor immune responses through attenuation of Treg cell-mediated immune suppression, which would lead to much enhanced treatment efficacy. The data presented here show that mIg-mGITRLs has the ability to attenuate the immune suppressive activity of CD4+CD25+ Treg cells in vitro. Intraperitoneal administration of mIg-mGITRLs with Ad.mGMCSF-IRES-mIL12 + mIg-m4-1BBLs treatment in 4T1-bearing mice resulted in tumor-free and long-term survival in >60% of the animals. Furthermore, this combination therapy induced robust tumor-specific CTL activities and the long-term surviving animals were able to reject a challenge of live parental tumor cells. There were no apparent toxic effects and taken together, the results suggest this novel combination therapy induced a systemic and effective anti-tumor immunity that is persistent, which may be translated into an effective and safe treatment modality for metastatic breast cancer in humans.
THE TREATMENT OF LUPUS ERYTHEMATOSUS WITH MEPACRINE AND PARA-AMINOBENZOIC ACID.
Authors: H. BLACK
Journal: British Journal of Dermatology (1953)

Journal Article THE TREATMENT OF LUPUS ERYTHEMATOSUS WITH MEPACRINE AND PARA‐AMINOBENZOIC ACID. Get access H. BLACK, M.B., M.R.A.C.R., M.R.C.P.Ed. H. BLACK, M.B., M.R.A.C.R., M.R.C.P.Ed. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 65, Issue 6, 1 June 1953, Pages 195–203, https://doi.org/10.1111/j.1365-2133.1953.tb13200.x Published: 01 June 1953
Flavonoid‐Modified Surfaces: Multifunctional Bioactive Biomaterials with Osteopromotive, Anti‐Inflammatory, and Anti‐Fibrotic Potential
Authors: Alba Córdoba, María Satué, Manuel Gómez‐Florit, Margarita Hierro‐Oliva, Christiane Petzold, Staale P. Lyngstadaas, María Luisa González‐Martín, Marta Monjo, Joana M. Ramis
Journal: Advanced Healthcare Materials (2014)

Flavonoids are small polyphenolic molecules of natural origin with antioxidant, anti-inflammatory, and antibacterial properties. Here, a bioactive surface based on the covalent immobilization of flavonoids taxifolin and quercitrin on titanium substrates is presented, using (3-aminopropyl)triethoxysilane (APTES) as coupling agent. FTIR and XPS measurements confirm the grafting of the flavonoids to the surfaces. Using 2-aminoethyl diphenylborinate (DPBA, a flavonoid-specific dye), the modified surfaces are imaged by fluorescence microscopy. The bioactivity of the flavonoid-modified surfaces is evaluated in vitro with human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and human gingival fibroblasts (HGFs) and compared to that of simple flavonoid coatings prepared by drop casting. Flavonoid-modified surfaces show anti-inflammatory and anti-fibrotic potential on HGF. In addition, Ti surfaces covalently functionalized with flavonoids promote the differentiation of hUC-MSCs to osteoblasts--enhancing the expression of osteogenic markers, increasing alkaline phosphatase activity and calcium deposition; while drop-casted surfaces do not. These findings could have a high impact in the development of advanced implantable medical devices like bone implants. Given the broad range of bioactivities of flavonoid compounds, these surfaces are ready to be explored for other biomedical applications, e.g., as stent surface or tumor-targeted functionalized nanoparticles for cardiovascular or cancer therapies.
Comorbidity of Mental Disorders and Nicotine Dependence
Authors: John R. Hughes
Journal: JAMA (1991)

To the Editor.—  It is ironic that the recent article by Regier et al, 1 Comorbidity of Mental Disorders With Alcohol and Other Drug Abuse, omitted the most important drug disorder: nicotine dependence. Nicotine dependence is recognized by DSM-III-R , 2 is especially common among psychiatric patients, 3-5 causes more death and disability than all the other drug disorders combined, 6 and is quite treatable. 6 Despite this, even the fact that nicotine dependence was omitted was not recognized in the article. Such scientific practices propagate the erroneous conclusion that (1) cigarette use is not a dependence disorder, (2) the consequences of nicotine dependence are not as significant as dependence on other drugs, or (3) treatment of smoking cessation is not the responsibility of physicians and psychiatrists.
Detection of common hepatitis C virus subtypes with a third-generation enzyme immunoassa
Authors: K R Huber, C Sebesta, K Bauer
Journal: Hepatology (1996)

The causal agent of most posttransfusion non-A and non-B hepatitis infections was characterized in 1989 by molecular biological techniques as a positive-stranded, enveloped RNA virus, designated hepatitis C virus (HCV). Only since 1990 has it been possible to screen for an infection with antibody tests or direct amplification assays for the nucleic acid (i.e., reverse-transcription polymerase chain reaction [PCR]). However, these nucleic acid based tests are time consuming and rather expensive. Recently, third-generation enzyme immunoassays (EIAs) for HCV infection were introduced (i.e., Abbott Laboratories, North Chicago, IL; Ortho Diagnostics, Inc., Raritan, NJ; and Roche Diagnostics, Basel, Switzerland). The Roche Diagnostics EIA has been evaluated with our patient population. To this end, 1,090 samples were assayed by both EIA and PCR; 946 of all samples (87%) were negative, and 107 samples (9.8%) were positive by both tests. Thirty of the patients (2.7%) showed antibodies but no detectable virus, whereas 7 of all patients tested (0.6%) were PCR-positive but had not yet developed antibodies to the virus. Of these 7 patients, only one showed normal serum transaminases. Virus strain subtyping and quantification of viral load on the positive samples in parallel have been performed, and the fact that the EIA detects all the virus subtypes found in our hospital can be inferred. No correlation between subtypes, viral load, and immune response could be measured with this antibody test. Our results indicate that, in most circumstances (except in settings where immunocompromised patients are abundant), this EIA can replace the much more expensive PCR tests for the routine screening for HCV infection.
Case 44-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Richard F. Spark, Sanford I. Roth
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 41-year old man was admitted to the hospital because of Cushing's syndrome.At the age of six years and again at 12 years he had rheumatic fever; a murmur was first detected at the age of eight years. At 25 years of age hypertension was found. Two and a half years before admission he entered another hospital because of angina pectoris; the diastolic blood pressure ranged between 90 and 100. Two months later acute myocardial infarction occurred, followed by episodes of angina. Twenty-three months before admission he came to this hospital for study. The blood pressure . . .
Urinary White-cell Excretion After Iron-sorbitol-Citric-acid
Authors: J. D. Briggs, A. C. Kennedy, A. Goldberg
Journal: BMJ (1963)

PSORIASIS AND POLYARTHRITIS described.Fifteen had consistently negative Rose-Waaler tests.Three had psoriasis, the remaining 13 being free from skin or nail lesions.One patient had an erosive arthritis with predominant terminal interphalangeal-joint involvement, absence of psoriasis, and negative Rose-Waaler tests.It is thought that this case is an example of psoriatic arthritis without psoriasis.Four patients, only one of whom had psoriasis, had radiological features suggestive of psoriatic arthritis.Criteria are presented to enable the diagnosis of psoriatic arthritis to be made in the absence of psoriasis.Although the remaining patients had a joint disease clinically and radiologically indistinguishable from rheuma- toid arthritis, all but one had consistently negative Rose- Waaler tests and none had subcutaneous nodules of rheumatoid type.The importance of seeking a family history of psoriasis and of making a thorough examination for psoriasis in patients with sero-negative polyarthritis of undetermined aetiology is stressed.The presence of even trivial psoriasis is important in patients with arthritis in view of the dangers of chloroquine therapy in this skin disease.We are indebted to Professor J. T. Ingram and Dr. G.
Urinary Tract Complications in the Prolonged Immobilization of Children
Authors: L. A. Key
Journal: BMJ (1936)

rrms~.,experiments of Lacassagne on young male mice are of intense interest.He injected oestrin into their bodies; the animals developed breasts in which carcinoma appeared in the majority of instances.There is no sug- gestion of inflammation to be observed in the micro- scopical sections he made of the succession of changes that ended in carcinoma.
Inebriates in the Army.
Authors: T. D. Crothers
Journal: JAMA (1898)

Hartford, Conn., July 20, 1898. <h3>To the Editor:</h3> —I have received two very urgent letters for my opinion on what is asserted to be facts in relation to the appointment of several persons to very responsible positions in the army. It is said that these persons are moderate and periodic drinkers of spirits, who are frequently intoxicated, and I am requested to write an opinion of such persons and their disabilities for such service. I can not say anything of the individual cases mentioned, but the same business principles should prevail here as in civil life. The moderate or periodic drinker is not considered a safe man in positions of responsibility, no matter what his capacity may be otherwise. In the early days of the Civil War, a number of inebriates were in responsible positions on both sides, and some way sad disaster followed their bad judgment. In those days
Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy
Authors: C Girmenia, R Latagliata, S Tosti, SG Morano, F Celesti, L Coppola, A Spadea, M Breccia, R Battistini, A Tafuri, G Cimino, F Mandelli, G Alimena
Journal: Leukemia (1999)
CELLULAR REQUIREMENTS FOR THE PRIMARY IN VITRO ANTIBODY RESPONSE TO DNP-FICOLL
Authors: D. E. Mosier, B. M. Johnson, W. E. Paul, P. R. B. McMaster
Journal: The Journal of Experimental Medicine (1974)

The cellular requirements for the primary in vitro IgM and IgG response to dinitrophenyl-substituted Ficoll were examined. Neither thymus-derived lymphocytes nor macrophage-rich splenic adherent cells were required for anti-DNP antibody synthesis. DNP-Ficoll is therefore tentatively classified as a "thymic-independent" antigen.
Pacing-induced Heterogeneities in Intracellular Ca <sup>2+</sup> Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart
Authors: Gary L. Aistrup, James E. Kelly, Sunil Kapur, Michael Kowalczyk, Inbal Sysman-Wolpin, Alan H. Kadish, J. Andrew Wasserstrom
Journal: Circulation Research (2006)

Optical mapping studies have suggested that intracellular Ca2+ and T-wave alternans are linked through underlying alternations in Ca2+ cycling-inducing oscillations in action potential duration through Ca2+-sensitive conductances. However, these studies cannot measure single-cell behavior; therefore, the Ca2+ cycling heterogeneities within microscopic ventricular regions are unknown. The goal of this study was to measure cellular activity in intact myocardium during rapid pacing and arrhythmias. We used single-photon laser-scanning confocal microscopy to measure Ca2+ signaling in individual myocytes of intact rat myocardium during rapid pacing and during pacing-induced ventricular arrhythmias. At low rates, all myocytes demonstrate Ca2+ alternans that is synchronized but whose magnitude varies depending on recovery kinetics of Ca2+ cycling for each individual myocyte. As rate increases, some cells reverse alternans phase, giving a dyssynchronous activation pattern, even in adjoining myocytes. Increased pacing rate also induces subcellular alternans where Ca2+ alternates out of phase with different regions within the same cell. These forms of heterogeneous Ca2+ signaling also occurred during pacing-induced ventricular tachycardia. Our results demonstrate highly nonuniform Ca2+ signaling among and within individual myocytes in intact heart during rapid pacing and arrhythmias. Thus, certain pathophysiological conditions that alter Ca2+ cycling kinetics, such as heart failure, might promote ventricular arrhythmias by exaggerating these cellular heterogeneities in Ca2+ signaling.
Regulation of rabbit medullary collecting duct cell pH by basolateral Na+/H+ and Cl-/base exchange.
Authors: M D Breyer, H R Jacobson
Journal: Journal of Clinical Investigation (1989)

The collecting duct of the inner stripe outer medulla (OMCDi) is a major site of distal nephron acidification. Using the pH sensitive fluorescent dye 2'-7'-bis(carboxyethyl)-5,6,-carboxyfluorescein (BCECF) and quantitative spectrofluorometry to measure intracellular pH in isolated perfused OMCDi, we have characterized basolateral transport processes responsible for regulation of intracellular pH. Experiments suggesting the existence of basolateral Cl-/base exchange were performed. In HCO3- containing buffers, bath Cl- replacement resulted in reversible alkalinization of the OMCDi from 7.22 +/- 0.05 to 7.57 +/- 0.12. Similarly 0.1 mM bath 4',4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) alkalinized the OMCDi from 7.14 +/- 0.09 to 7.34 +/- 0.09 and blocked further alkalinization by bath Cl- removal (delta = + 0.02 pH units). The concentration dependence kinetics of Cl-/base exchange revealed a K1/2 of 10 mM for external Cl- with a Vmax of 0.50 pH U/min. Experiments suggesting the existence of basolateral Na+/H+ exchange were also performed. Replacement of bath Na+ by tetramethylammonium resulted in reversible cell acidification (7.14 +/- 0.09 to 6.85 +/- 0.1). Tubules that were acidified by a brief exposure to NH4Cl displayed recovery of cell pH back to baseline at a rate that was highly dependent on bath Na+ concentration. Half maximal recovery rate was achieved at 7 mM bath Na+ and Vmax was 0.605 pH U/min. The Na+-dependent rate of cell pH recovery after acidification was blocked by 0.2 mM bath amiloride. These results suggest that intracellular pH in the OMCDi is regulated by parallel basolateral Na+/H+ exchange and Cl-/base exchange.
Abstract 2689: Inhibition of metastasis of circulating tumor cells by extracellular matrix secreted by human embryonic cells
Authors: Rhiana Menen, Emmett Pinney, Mohamed K. Hassanein, Michael Bouvet, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract We have previously demonstrated the increased metastatic potential of human prostate cancer PC-3 CTCs compared to their parental counterparts in both chick embryo and mouse models. In the present study, we tested the effects of human embryonic extracellular matrix (ECM), secreted by human embryonic cells including conditioned medium (CM) and a semi-solid form (hECM), on metastasis of PC-3 CTC in the chick embryo model. The chorioallentoic membrane (CAM) of 18 chicken embryos were inoculated with either 106 PC-3 human prostate cancer cells or PC-3 CTCs, both stably expressing GFP. Twelve hours later, embryos were divided into 6 groups each containing three embryos: PC-3 parental control; PC-3 + CM; PC-3 + hECM; CTC control; CTC + CM; and CTC+ hECM. Twelve hours following inoculation of the cells, a single dose of 100 μL of either treatment was given to the appropriate group. Embryo brains were removed on day 8 post-inoculations, and processed for cryo-sectioning, generating 3 slides of brain tissue per embryo taken at various depths. Imaging was performed using the IV-100 scanning laser microscope (Olympus Corp, Tokyo, Japan) in order to count metastatic foci. PC-3 controls had an average of 11.1 metastatic foci compared to 2.55 in the PC-3 + hECM group (p&amp;lt; 0.0001) and 2.76 in the PC-3 + CM group (p&amp;lt; 0.0001) The treatment showed even greater response on the CTC cells which an average of 30.9 metastatic foci in the CTC controls compared to 4.38 in the CTC + hECM group (p&amp;lt; 0.0001) and 4.18 in the CTC + CM group (p&amp;lt; 0.0001). Thus, human embryonic secreted ECM compound drastically decreased the metastatic potential of human prostate cancer CTCs in the chick embryo model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2689. doi:1538-7445.AM2012-2689
Temporal Dynamics of the Human Vaginal Microbiota
Authors: Pawel Gajer, Rebecca M. Brotman, Guoyun Bai, Joyce Sakamoto, Ursel M. E. Schütte, Xue Zhong, Sara S. K. Koenig, Li Fu, Zhanshan (Sam) Ma, Xia Zhou, Zaid Abdo, Larry J. Forney, Jacques Ravel
Journal: Science Translational Medicine (2012)

Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
Book Review Blood Feuds: AIDS, blood, and the politics of medical disaster Edited by Eric A. Feldman and Ronald Bayer. 375 pp. New York, Oxford University Press, 1999. $29.95 (paper); $49.50 (cloth). 0-19-513160-6 (paper); 0-19-512929-6 (cloth).
Authors: James W. Curran
Journal: New England Journal of Medicine (1999)
Modulation of Cytokine Expression in Human Myeloid Dendritic Cells by Environmental Endocrine-Disrupting Chemicals Involves Epigenetic Regulation
Authors: Chih-Hsing Hung, San-Nan Yang, Po-Lin Kuo, Yu-Te Chu, Hui-Wen Chang, Wan-Ju Wei, Shau-Ku Huang, Yuh-Jyh Jong
Journal: Environmental Health Perspectives (2009)

Exposure to environmental endocrine-disrupting chemicals (EDCs) is often associated with dysregulated immune homeostasis, but the mechanisms of action remain unclear.The aim of this study was to test a hypothesis that EDCs regulate the functions of human dendritic cells, a front-line, immunoregulatory cell type in contact with the environment.We investigated circulating myeloid dendritic cells (mDCs) from five subjects and measured their responses, with or without coculture with autologous T cells, to two common EDCs, nonylphenol (NP) and 4-octylphenol (4-OP). EDC-associated cytokine responses, signaling events, and histone modifications were examined using ELISA, Western blotting, and chromatin immunoprecipitation (ChIP) assays, respectively.In all cases, mDCs treated with NP or 4-OP demonstrated increased expression of tumor necrosis factor-alpha (TNF-alpha) but decreased baseline and lipopolysaccharide (LPS)-induced (interleukin) (IL)-10 production; the increase in TNF-alpha was partially reversible by an estrogen receptor (ER) antagonist. Activation of the MKK3/6-p38 signaling pathway marked the effect of NP on TNF-alpha expression, concomitant with enhanced levels of methyltranferase complex [mixed-lineage leukemia (MLL) and tryptophan-aspartic acid repeat domain 5 (WDR5)] in the nucleus and of trimethylated H3K4, acetylated H3, and H4 at the TNFA gene locus. Further, up-regulated TNF-alpha expression was significantly suppressed in NP-treated mDCs by a histone acetyltransferase inhibitor. In the presence of NP-treated mDCs, T cells showed increased levels of IL-13 but decreased expression of interferon-gamma.These results suggest that NP and 4-OP may have functional effects on the response of mDCs via, in part, the ER, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent influence on the T-cell cytokine responses.
In Vivo Expansion of Regulatory T cells With IL-2/IL-2 mAb Complexes Prevents Anti-factor VIII Immune Responses in Hemophilia A Mice Treated With Factor VIII Plasmid-mediated Gene Therapy
Authors: Chao-Lien Liu, Peiqing Ye, Benjamin C Yen, Carol H Miao
Journal: Molecular Therapy (2011)

Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.