tbuckley/cabot-search huggingface dataset:
Measurement of brevetoxin levels by radioimmunoassay of blood collection cards after acute, long-term, and low-dose exposure in mice.
Authors: Ricky Woofter, M-Yasmine Bottein Dechraoui, Ian Garthwaite, Neale R Towers, Christopher J Gordon, José Córdova, John S Ramsdell
Journal: Environmental Health Perspectives (2003)

We developed a radioimmunoassay (RIA) using a sheep anti-brevetoxin antiserum to evaluate detection of brevetoxin on blood collection cards from mice treated with the brevetoxin congener PbTx-3. The RIA has high affinity for PbTx-3 [half-maximal effective concentration (EC(50)) +/- SE = 1.2 +/- 0.2 nM; n = 10] and recognizes both type 1 and type 2 brevetoxins, but not ciguatoxin. Direct comparison of the RIA with a radiolabeled [(3)H]-PbTx-3 receptor-binding assay (RBA) revealed excellent sensitivity, congener selectivity, and minimal interference from blood matrix. We first analyzed blood samples from an acute time course exposure, using a maximal nonlethal dose [180 microg/kg body weight (bw)] for 0.5, 1, 2, 4, and 24 hr. Mean blood brevetoxin levels were 36 nM at 30 min and stayed above 20 nM during the 1-4 hr time points. We next analyzed blood brevetoxin levels after longer exposure (0.5, 1, 2, 3, 4, or 7 days). Mean blood brevetoxin levels were 26.0 nM at 0.5 days, decreased to 8.2 nM at 1.0 day, and maintained a significant level (p < 0.05) of 1.3 nM at day 2. We next determined the lowest measurable dose using increasing concentrations of PbTx-3 (10-300 micro g/kg bw). Analysis of the blood samples at 60 min revealed a linear relationship between administered and internal doses (r(2) = 0.993). All doses of brevetoxin administered were detectable at 1 hr, with significant levels found for the lowest administered dose of 10 micro g/kg bw--a dose that was 10-fold lower than the lowest observable effect level. This RIA provides an optimal first-tier detection of brevetoxin from blood collection cards and, used in combination with the RBA and liquid chromatography-mass spectrometry, should provide a complete panel of methods to biomonitor brevetoxin exposure.
Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production
Authors: Dagmar Breitfeld, Lars Ohl, Elisabeth Kremmer, Joachim Ellwart, Federica Sallusto, Martin Lipp, Reinhold Förster
Journal: The Journal of Experimental Medicine (2000)

Chemokines and their receptors have been identified as major regulators controlling the functional organization of secondary lymphoid organs. Here we show that expression of CXC chemokine receptor 5 (CXCR5), a chemokine receptor required for B cell homing to B cell follicles, defines a novel subpopulation of B helper T cells localizing to follicles. In peripheral blood these cells coexpress CD45RO and the T cell homing CC chemokine receptor 7 (CCR7). In secondary lymphoid organs, CD4(+)CXCR5(+) cells lose expression of CCR7, which allows them to localize to B cell follicles and germinal centers where they express high levels of CD40 ligand (CD40L), a costimulatory molecule required for B cell activation and inducible costimulator (ICOS), a recently identified costimulatory molecule of the CD28 family. Thus, when compared with CD4(+)CD45RO(+)CXCR5(-) cells, CD4(+)CD45RO(+)CXCR5(+) tonsillar T cells efficiently support the production of immunoglobulin (Ig)A and IgG. In contrast, analysis of the memory response revealed that long-lasting memory cells are found within the CD4(+)CD45RO(+)CXCR5(-) population, suggesting that CXCR5(+)CD4 cells represent recently activated effector cells. Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells "follicular B helper T cells" (T(FH)).
P1158 EFFICACY AND SAFETY OF BOCEPREVIR-BASED THERAPY IN HCVG1 TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED FIBROSIS/CIRRHOSIS: THE ITALIAN AND SPANISH NPP EARLY ACCESS PROGRAM
Authors: S. Bruno, S. Bollani, J.M. Pascasio, A.L. Zignego, V. Di Marco, C. Magni, M. Rizzetto, A. Ciancio, A. Alberti, S. Piovesan, A. Mangia, J. De la Revilla, J.R. Larrubia, F. Gea, S. Babudieri, R. Perez-Alvarez, C. Colletta, R. Barcena, X. Forns, M. Romero-Gomez, M. Koch, M. Massari, M. Caremani, J. Crespo, J.M. Navarro, J. Arenas, M.B. Delgado, M. Pirisi, M. Zuin, A. Licata, F. Mazzotta, A. Colombo, M. Russello, I. Fermandez, T. Santantonio, C.M. Fernandez-Rodriguez, F. Farina, B. Ruiz Antoran, P. Maisonneuve, A. Craxì, J.L. Calleja
Journal: Journal of Hepatology (2014)
Abstract 4519: In vitro cell and in vivo animal studies of the demethylating agent in treating HER2-amplified breast cancer
Authors: Pang-Kuo Lo, Deepak Kanojia, Hexin Chen
Journal: Cancer Research (2011)

Abstract PURPOSE: The recent evidence shows that HER2-amplified breast cancers exhibit more frequent CpG island methylation than other types of breast cancers, suggesting epigenetic alterations are involved in HER2-mediated tumorigenesis. In this study, we addressed the possibility of the use of the demethylating agent (5-aza-2’-deoxycytidine, decitabine) for treatment of HER2-overexpressing breast cancer. EXPERIMENTAL DESIGN: Two cell model systems were used in this study: murine primary Her2-overexpressing tumor cell line (A6O5, derived from the tumor naturally developed in HER2/neu transgenic mice) and human HER2-overexpressing luminal breast cancer cell line MCF7-HER2-18. Cells were cultured in regular cell culture dishes with the serum-containing medium (adhesive culture) or in ultra-low attachment dishes with the serum-free sphere culture medium (tumorsphere culture) for drug testing. Tumors developed from A6O5 cells injected into mammary glands of HER2/neu transgenic mice were used as the xenograft model. The early spontaneous mammary tumors naturally developed in HER2/neu transgenic mice (size &amp;lt; 5 mm) were used for drug treatment. RESULTS: The in vitro growth of A6O5 was more significantly inhibited by decitabine than that of non-tumorigenic murine mammary epithelial cells. Consistently, MCF7-HER2-18 cells were more sensitive to decitabine-induced growth suppression than its control vector-transfected cell line MCF7-Neo. These results suggest that HER2 overexpression renders cancer cells more sensitive to the effect of decitabine. Surprisingly, the tumorsphere formation of A6O5 and MCF7-HER2-18 was dramatically abrogated by decitabine, suggesting that self-renewal of cancer stem cells in these two cell lines was annihilated by decitabine. Importantly, decitabine inhibited the in vivo growth of A6O5 xenograft tumors. For proof-in-principle of this study, we treated the HER2/neu transgenic mice bearing early developing mammary tumors with decitabine. Indeed, decitabine effectively suppressed the in vivo tumor growth of the decitabine-treated group compared to that of the vehicle-treated group. CONCLUSIONS: This study for the first time explores the potential of the demethylating agent in the treatment of HER2-amplified breast cancers using in vitro cell and in vivo animal models. These findings shed light on the translational application of epigenetic modifiers with the HER2-signaling blockers to treatment of HER2-amplified breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4519. doi:10.1158/1538-7445.AM2011-4519
Nasal administration of birch pollen allergen formulated with proteosomeTM adjuvant to sensitized mice induces increased IFN-γ and IgG2a that persist and are associated with suppression of increases in antigen-specific IgE following allergen challenge
Authors: C.R. Rioux, A.M. Gelinas, H. Diamantakis, N. Bellerose, S. Tran, M. Plante, G.H. Lowell, D.S. Burt
Journal: Journal of Allergy and Clinical Immunology (2003)
Extracorporeal photochemotherapy induces apoptosis of infiltrating lymphoid cells in patients with mycosis fungoides in early stages. A quantitative histological study
Authors: C. MIRACCO, P. RUBEGNI, G. DE ALOE, G. D'ASCENZO, C. MAZZATENTA, M.M. DE SANTI, M. FIMIANI
Journal: British Journal of Dermatology (1997)

Extracorporeal photochemotherapy (ExP) is a well-tolerated new form of chemoimmunotherapy, which is considered to be effective for cutaneous T-cell lymphoma (CTCL) and the treatment of choice for Sézary syndrome. Improvements have also been seen in patients with non-erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells are not detectable in the peripheral blood. In this study, we used ExP as a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other therapies. We observed a clinical improvement in the disease after 12 months of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin biopsies of large plaque lesions before and after the treatment. We undertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following parameters; lymphoid cell density (LCD), Ki67 + lymphoid cell nuclei percentage (Ki67 + Lcn percentage), and apoptotic index (AI). Significant decreases in the lymphoid cell infiltrate and in cell proliferation, and a significant increase in AI were observed after therapy. The mean LCD decreased from 187 +/- 33 to 34 +/- 17.7, Ki67 + Lcn mean percentage decreased from 16.9 +/- 3.9 to 4.9 +/- 2.4, and the AI mean value increased from 0.05 +/- 0.03 to 2.41 +/- 1.54. Our results suggest a role for apoptosis in the improvement of the skin lesions and are in line with some reports on the mode of action of ExP. Although the way in which ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell-mediated anticlonotypic activity against circulating pathogenic clones. Furthermore, a release of tumour necrosis factor alpha (TNF-alpha) by circulating monocytes has been demonstrated after ExP. Both are known to induce cell death by apoptosis.
Chromate-induced epimutations in mammalian cells.
Authors: Catherine B Klein, Lin Su, Darlene Bowser, Joanna Leszczynska
Journal: Environmental Health Perspectives (2002)

Epigenetic gene silencing by aberrant DNA methylation of gene promoter regions is a nonmutagenic but heritable epigenetic mechanism that may mistakenly cause the silencing of important cancer-related tumor suppressor genes. Using a transgenic, V79-derived, mammalian cell line (G12) that contains a bacterial gpt reporter gene in its DNA, we can study carcinogen-induced gene inactivation by mutagenic as well as epigenetic DNA methylation mechanisms. Whereas numerous carcinogens have previously been shown to be mutagenic in these cells, a few carcinogens, including nickel, diethylstilbestrol, and X-rays, are also capable of silencing the G12 cell gpt transgene by aberrant DNA methylation. Here we report for the first time that carcinogenic potassium chromate salts can also induce aberrant DNA methylation in this system. In contrast insoluble barium chromate produced significant level of mutations in these cells but did not cause DNA methylation changes associated with transgene expression.
Biological responses in stented arteries
Authors: Chiraz Chaabane, Fumiyuki Otsuka, Renu Virmani, Marie-Luce Bochaton-Piallat
Journal: Cardiovascular Research (2013)

Vascular walls change their dimension and mechanical properties in response to injury such as balloon angioplasty and endovascular stent implantation. Placement of bare metal stents induces neointimal proliferation/restenosis which progresses through different phases of repair with time involving a cascade of cellular reactions. These phases just like wound healing comprise distinct steps consisting of thrombosis, inflammation, proliferation, and migration followed by remodelling. It is noteworthy that animals show a rapid progression of healing after stent deployment compared with man. During stenting, endothelial cells are partially to completely destroyed or crushed along with medial wall injury and stretching promoting activation of platelets, and thrombus formation accompanied by inflammatory reaction. Macrophages and platelets play a central role through the release of cytokines and growth factors that induce vascular smooth muscle cell accumulation within the intima. Smooth muscle cells undergo complex phenotypic changes including migration and proliferation from the media towards the intima, and transition from a contractile to a synthetic phenotype; the molecular mechanisms responsible for this change are highlighted in this review. Since studies in animals and man show that smooth muscle cells play a dominant role in restenosis, drugs like rapamycin and paclitaxel have been coated on stent with polymers to allow local slow release of drugs, which have resulted in dramatic reduction of restenosis that was once the Achilles' heel of interventional cardiologists.
MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma
Authors: Wei-Chih Tsai, Paul Wei-Che Hsu, Tsung-Ching Lai, Gar-Yang Chau, Ching-Wen Lin, Chun-Ming Chen, Chien-Der Lin, Yu-Lun Liao, Jui-Ling Wang, Yat-Pang Chau, Ming-Ta Hsu, Michael Hsiao, Hsien-Da Huang, Ann-Ping Tsou
Journal: Hepatology (2008)

MicroRNAs (miRNAs), which are inhibitors of gene expression, participate in diverse biological functions and in carcinogenesis. In this study, we show that liver-specific microRNA-122 (miR-122) is significantly down-regulated in liver cancers with intrahepatic metastasis and negatively regulates tumorigenesis. Restoration of miR-122 in metastatic Mahlavu and SK-HEP-1 cells significantly reduced in vitro migration, invasion, and anchorage-independent growth as well as in vivo tumorigenesis, angiogenesis, and intrahepatic metastasis in an orthotopic liver cancer model. Because an inverse expression pattern is often present between an miRNA and its target genes, we used a computational approach and identified multiple miR-122 candidate target genes from two independent expression microarray datasets. Thirty-two target genes were empirically verified, and this group of genes was enriched with genes regulating cell movement, cell morphology, cell-cell signaling, and transcription. We further showed that one of the miR-122 targets, ADAM17 (a disintegrin and metalloprotease 17) is involved in metastasis. Silencing of ADAM17 resulted in a dramatic reduction of in vitro migration, invasion, in vivo tumorigenesis, angiogenesis, and local invasion in the livers of nude mice, which is similar to that which occurs with the restoration of miR-122.Our study suggests that miR-122, a tumor suppressor microRNA affecting hepatocellular carcinoma intrahepatic metastasis by angiogenesis suppression, exerts some of its action via regulation of ADAM17. Restoration of miR-122 has a far-reaching effect on the cell. Using the concomitant down-regulation of its targets, including ADAM17, a rational therapeutic strategy based on miR-122 may prove to be beneficial for patients with hepatocellular carcinoma.
Drug eluting stents remain a "major concern" in the longer term, finds study
Authors: D. Spurgeon
Journal: BMJ (2009)

A three year Canadian study of more than 6000 patients who had an angioplasty with either drug eluting or bare metal stents concludes that the medicated version, now used in 85% of procedures in the United States and in 40% or more elsewhere, could be associated with longer term adverse events ( CMAJ 2009;180:167-74, doi:10.1503/cmaj.080050).

An accompanying commentary, from Columbia University Medical Centre, New York, notes that “despite the large and favourable long-term data on the use of drug-eluting stents from randomised controlled trials, meta-analyses and observational studies, the long-term safety of drug-eluting stents, especially regarding late and very late stent thrombosis, …
Abstract 4871: Genomic amplifications in ovarian carcinoma are associated with specific histone modifications
Authors: Michelle M. Thiaville, Tian-Li Wang, Ie-Ming Shih, Lily Chen, Jianghui Xiong, Jason J. Xuan
Journal: Cancer Research (2010)

Abstract Genomic amplification is a frequent molecular genetic alteration in many cancer types that results in upregulation and thus activation of oncogenes located in the amplified regions. However, the mechanism by which amplified genes are upregulated is poorly understood. We hypothesized that epigenetic regulation of gene expression was important for activation in addition to the increased DNA copy number for genes within amplified genomic loci. To test this hypothesis, we used ovarian cancer as an example because it is a highly lethal disease and, more importantly, ovarian cancer cells are characterized by a high level of genomic instability as reflected by widespread DNA copy number changes. We analyzed the data from chromatin immunoprecipitation array (Chip-chip) and single nucleotide polymorphism (SNP) array to determine the correlation between specific histone modifications and genome-wide DNA copy number alterations in OVCAR3 ovarian cancer cells and ovarian surface epithelial cell culture. Among 8 histone marks examined, representing both heterochromatic and euchromatic chromatin, we identified the strongest correlation between increased DNA copy number and the active histone marks, histone H4 acetylation at lysine 5 (p-value 7.8×10^-6; FDR 5.2×10^-5) and lysine 12 (p-value 7.6×10^-5; FDR 2.6×10^-4). In contrast, there was no significant correlation between DNA amplification and repressive histone marks including histone H3 methylation at lysines 9 and 27. These correlations were validated by quantitative real-time PCR of ChIP samples at confirmed amplified regions on chromosomes 11 and 19, which harbor the RSF1 and AKT2 oncogenes. Furthermore, all genes within the amplicons were overexpressed in the OVCAR3 cell line harboring the amplicons as compared to a normal ovarian surface epithelial cell line. By using ovarian cancer as a disease model, our results indicate that an amplicon-associated specific histone modification pattern facilitates gene expression and suggest that both genetic (DNA copy number gain) and epigenetic (active histone marks) events contribute to upregulation of amplified genes which may ultimately contribute to the development of human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4871.
Insulin-Like Growth Factors and Ovarian Follicular Development*
Authors: LINDA C. GIUDICE
Journal: Endocrine Reviews (1992)

INSULIN-like growth factor-I (IGF-I) and its structural homologue, IGF-II, are low molecular weight peptides that promote cellular mitosis and differentiation in a variety of systems and are believed to play a role in cyclic ovarian follicular development. In 1978, IGF-I and IGF-II were purified and sequenced by Rinderkneckt and Humbel (1, 2), and since that time there has been an exponential accumulation of information regarding these peptides, as well as their receptors, and their binding proteins (IGFBPs), constituents of the "IGF autocrine/paracrine system." These constituents have been examined in various tissues in vivo under a variety of physiological conditions and in vitro in numerous cell and tissue culture systems in several species (for review see Refs. 3–9). A decade ago, research on the IGFs focused on skeletal growth in childhood, a subspecialty of pediatric endocrinology. In the intervening years, the arena of research inquiry extended to other disciplines, including nephrology, ophthalmology, adult endocrinology, surgery, genetics, and reproductive endocrinology. Adashi and colleagues (10) published in 1985, in this journal, an elegant and comprehensive monograph describing what was known at that time about the IGFs and their roles as intraovarian regulators of granulosa cell growth and function. New information on the IGF system in the ovary has been accumulating rapidly during the years since Adashi's review, mainly due to two major advances in science and medicine. First, advances in molecular biology have provided details of the structures of the IGFs, IGFBPs, and IGF receptors. Complementary and genomic DNA for most of the components of the IGF system have been cloned and sequenced (reviewed in Refs. 3–9), opening the way for understanding regulation and function of these peptides and proteins in the ovary, as well as in other tissues. Second, the clinical practice of reproductive endocrinology has been revolutionized by the advent of in vitro fertilization and embryo transfer (IVF-ET) as treatment for infertility due to a variety of causes. Follicular growth, in response to exogenous gonadotropin administration, can be observed by ultrasound, and human granulosa cells, components of follicular aspirates during oocyte retrieval for IVF-ET, have become plentiful for examination in the laboratory. In addition, the repertoire of agents used for ovulation induction for IVF-ET has increased, and GH, the main regulator of serum IGF-I levels, has been included as an adjunct to gonadotropins in some ovulation induction protocols. Along with studies on human follicular constituents and granulosa cells obtained from follicles exposed to a variety of ovulation induction agents, continued basic research in animal models has brought comparative physiology of normal and abnormal ovarian function into a new age of investigation.
BILATERAL CANCER OF THE BREAST IN THE FEMALE FOLLOWING PROLONGED IRRITATION
Authors: Robert B. McGraw
Journal: JAMA (1924)

An unmarried woman, aged 41, was admitted to the Second Medical Service at Bellevue Hospital, under Dr. Eugene Du Bois, Aug. 9, 1923, complaining of stabbing pains of four months' duration in the sacrum; the pains radiated to the right leg and to the amputation stump of the left leg. The patient stated that, at the age of 8, the left leg had been amputated at the midthigh, because of injury. Immediately after operation, she wore a crutch on the left side and has continued to do so ever since. At 23, pain in the right kidney region and urinary symptoms led to an exploratory operation, which disclosed a tuberculous kidney, and a nephrectomy was done. Just before this, the patient had fallen and fractured the right patella. This was repaired, by open operation, at the same time that the nephrectomy was done. After this operation, she used two crutches
The TEMPI Syndrome — A Novel Multisystem Disease
Authors: David B. Sykes, Wilfried Schroyens, Casey O'Connell
Journal: New England Journal of Medicine (2011)

To the Editor: The description of a man with erythrocytosis and perinephric fluid collections recently appeared in the Case Records of the Massachusetts General Hospital1 (Patient 1 in Table 1), and the authors of that article appealed to readers to share similar cases. Two additional patients were identified (Patients 2 and 3), and a review of the literature identified three more patients with similar findings2–4 (Patients 4, 5, and 6). These six patients shared five characteristics — telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric-fluid collections, and intrapulmonary shunting — defining a syndrome that we have termed the TEMPI . . .