tbuckley/cabot-search huggingface dataset:
GABAergic Excitation of Vasopressin Neurons
Authors: Young-Beom Kim, Yoon Sik Kim, Woong Bin Kim, Feng-Yan Shen, Seung Won Lee, Hyun Joo Chung, Jeong Sook Kim, Hee Chul Han, Christopher S. Colwell, Yang In Kim
Journal: Circulation Research (2013)

Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension.Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension.In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA(A) agonist) microinjection into the supraoptic nuclei in hypertensive rats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection.We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na(+)-dependent hypertension.
Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice
Authors: Karrie K. Wong, Fred Brenneman, Alden Chesney, David E. Spaner, Reginald M. Gorczynski
Journal: Cancer Research (2012)

Abstract CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy controls, and there was a significant correlation with CLL disease stage. Infusion of sCD200hi CLL plasma into severely immunocompromised NOD.SCIDγcnull (NSG) mice enhanced the engraftment of CLL splenocytes as compared with mice receiving sCD200lo normal plasma. CLL cells were detected in both the spleen and peritoneal cavity of animals for up to 75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3 monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating engrafted CLL cells when administered 21 days after engraftment. Taken together, our findings point to sCD200 as a novel prognostic marker and therapeutic target for CLL. Furthermore, the humanized mouse model described here may prove valuable to preclinically assess new treatment regimens for CLL. Cancer Res; 72(19); 4931–43. ©2012 AACR.
Comment on: Tam et al. Defining Insulin Resistance From Hyperinsulinemic-Euglycemic Clamps. Diabetes Care 2012;35:1605–1610
Authors: Mayer B. Davidson
Journal: Diabetes Care (2012)

The euglycemic-hyperinsulinemic clamp is the gold standard for evaluating insulin sensitivity. As such, it is extremely helpful in evaluating the effect of an intervention or in comparing insulin sensitivities between two or more groups. What remains a challenge is to decide the values above which …
Effect of an Aqueous Extract of Cigarette-Smoke Condensate on Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene-Induced Sarcoma and Body Weight in the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K L Sydnor, C Allen, B Higgins
Journal: JNCI Journal of the National Cancer Institute (1972)
Immunobiomarkers in Small Cell Lung Cancer: Potential Early Cancer Signals
Authors: Caroline J. Chapman, Alison J. Thorpe, Andrea Murray, Celine B. Parsy-Kowalska, Jared Allen, Kelly M. Stafford, Alok S. Chauhan, Thomas A. Kite, Paul Maddison, John F. R. Robertson
Journal: Clinical Cancer Research (2010)

We investigated the presence of autoantibodies as immunobiomarkers to a panel of tumor-associated antigens in a group of individuals with small cell lung cancer (SCLC), a disease group that has a poor overall cancer prognosis and therefore may benefit most from early diagnosis.Sera from 243 patients with confirmed SCLC and normal controls matched for age, sex, and smoking history were analyzed for the presence of these early immunobiomarkers (i.e., autoantibodies to p53, CAGE, NY-ESO-1, GBU4-5, Annexin I, SOX2, and Hu-D) by ELISA.Autoantibodies were seen to at least 1 of 6 antigens in 55% of all the SCLC patients' sera tested, with a specificity of 90% compared with controls. Using a higher assay cutoff to achieve a specificity of 99%, autoantibodies were still detectable in 42% of SCLC patients (receiver operator characteristic area under the curve = 0.76). There was no significant difference in sensitivity when analyzed by stage of the cancer or by patient age or gender. The frequency of autoantibodies to individual antigens varied, ranging from 4% for GBU4-5 to 35% for SOX2. Levels of Annexin I autoantibodies were not elevated in patients with SCLC. Antibodies were also detected in 4 separate patients whose sera were taken up to 3 months before tumor diagnosis.The presence of an autoantibody to one or more cancer-associated antigens may provide an important addition to the armamentarium available to the clinician to aid early detection of SCLC in high-risk individuals.
Controlling Salmonella along the food chain in the European Union - progress over the last ten years
Authors: M Hugas, P A Beloeil
Journal: Eurosurveillance (2014)

Preview this article: Controlling Salmonella along the food chain in the European Union - progress over the last ten years, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/19/art20804-en-1.gif
mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients
Authors: Anieta M. Sieuwerts, Bianca Mostert, Joan Bolt-de Vries, Dieter Peeters, Felix E. de Jongh, Jacqueline M.L. Stouthard, Luc Y. Dirix, Peter A. van Dam, Anne Van Galen, Vanja de Weerd, Jaco Kraan, Petra van der Spoel, Raquel Ramírez-Moreno, Carolien H.M. van Deurzen, Marcel Smid, Jack X. Yu, John Jiang, Yixin Wang, Jan W. Gratama, Stefan Sleijfer, John A. Foekens, John W.M. Martens
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer. Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule–based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors. Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels. Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs. Clin Cancer Res; 17(11); 3600–18. ©2011 AACR.
Triterpenoid Electrophiles (Avicins) Suppress Heat Shock Protein-70 and X-Linked Inhibitor of Apoptosis Proteins in Malignant Cells by Activation of Ubiquitin Machinery: Implications for Proapoptotic Activity
Authors: Amos Gaikwad, Ann Poblenz, Valsala Haridas, Chunlei Zhang, Madeleine Duvic, Jordan Gutterman
Journal: Clinical Cancer Research (2005)

Abstract Avicins are plant-derived triterpenoid stress metabolites that have both proapoptotic and cytoprotective properties. Avicins induce apoptosis in Jurkat T leukemia cells by targeting mitochondria and release of cytochrome c that occurs in a p53-independent manner. However, postmitochondrial antiapoptotic barriers, such as increased expression of heat shock proteins (Hsp) and X-linked inhibitor of apoptosis proteins (XIAP), frequently exist in cancer cells and often account for resistance to chemotherapy and a poor prognosis. In this article, we show the role of avicins in the activation of stress-regulated ubiquitination and degradation of Hsp70 and XIAP. This is the first report showing the regulation of Hsp70 via the ubiquitin/proteasome pathway. We also show the induction of E3α ubiquitin ligase in avicin-treated Jurkat T leukemia cells, and its involvement in the degradation of XIAP. Avicin-mediated suppression of Hsp70 and XIAP was further confirmed in other leukemic/lymphoma cell lines and freshly isolated peripheral blood lymphocytes from Sezary syndrome patients. No change in the Hsp70 and XIAP proteins was observed in peripheral blood lymphocytes from normal donors. We propose that the ability of avicins to induce ubiquitination and regulate the degradation of Hsp70 and XIAP in leukemia cells could have important implications in the treatment of drug-resistant neoplasia and inflammatory disorders.
Lateral interactions in the superior colliculus, not an extended fixation zone, can account for the remote distractor effect
Authors: E. Olivier, M. C. Dorris, D. P. Munoz
Journal: Behavioral and Brain Sciences (1999)

Recordings of neuronal activity in the monkey superior colliculus (SC) suggest that the two apparently independent effects of a visual distractor on both temporal (latency) and spatial (metrics) saccade parameters may be the result of lateral interactions between subpopulations of saccade-related neurons located at different sites on the motor map of the superior colliculus. One subpopulation is activated during the planing and initiation of a saccade; the other is activated by the appearance of a distractor. The inhibitory or facilitative nature of this interaction depends on the distance between the distractor and the target and is consistent with the complex pattern of intrinsic and commissural collicular connections.
Haemodynamic Action of Thymoxamine (An Alpha-adrenergic Blocking Agent) in Occlusive Peripheral Arterial Disease
Authors: K. A. Myers, J. T. Hobbs, W. T. Irvine
Journal: Cardiovascular Research (1968)

Journal Article Haemodynamic Action of Thymoxamine (An Alpha-adrenergic Blocking Agent) in Occlusive Peripheral Arterial Disease Get access K. A. Myers, K. A. Myers * From the Surgical Unit, St. Mary's Hospital, London * Present address: Royal Melbourne Hospital, Australia. In receipt of a Smith and Nephew Fellowship and of a supplementary grant from the National Heart Foundation of Australia. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. T. Hobbs, J. T. Hobbs From the Surgical Unit, St. Mary's Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar W. T. Irvine W. T. Irvine From the Surgical Unit, St. Mary's Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 4, October 1968, Pages 360–366, https://doi.org/10.1093/cvr/2.4.360 Published: 01 October 1968 Article history Received: 14 December 1967 Published: 01 October 1968
The Birmingham COPD cohort study - Associations between CAT, lung health and health care use
Authors: Andy Dickens, Peymane Adab, Rachel Jordan, Alexandra Enocson, Jon Ayres, David Fitzmaurice
Journal: European Respiratory Journal (2013)

Introduction:  The COPD Assessment Test (CAT) gauges the impact of COPD on patients’ daily lives and now forms a key part of GOLD management recommendations. Longitudinal cohort studies are needed to better understand the utility of CAT in a primary care-based population.  Aims and objectives:  Using a primary care cohort, we will explore whether aspects of lung health and health care use are associated with CAT.  Methods:  Patients from primary care COPD registers were recruited into a three-year cohort study. An interim dataset was used to assess associations between CAT scores, lung health and health care use at baseline.  Results:  600 patients have been recruited so far, of which 13% had FEV1/FVC>70% and 73.4% fulfilled the LLN criteria for COPD. Patients with confirmed COPD had a mean CAT score of 20.4 (SD 9.0). Forced expiratory volume in 1 second (FEV1) % predicted was negatively associated with CAT (p  Conclusions:  CAT scores are strongly associated with lung health, health service use and co-morbidities. Pending longitudinal analysis, the data suggest CAT is useful in early identification of patients at risk of hospitalisation.
Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease
Authors: Hong Zheng, Catherine Matte-Martone, Hongmei Li, Britt E. Anderson, Srividhya Venketesan, Hung Sheng Tan, Dhanpat Jain, Jennifer McNiff, Warren D. Shlomchik
Journal: Blood (2007)
Lymphadenopathy-Associated-Virus Infection and Acquired Immunodeficiency Syndrome
Authors: J C Gluckman, D Klatzmann, L Montagnier
Journal: Annual Review of Immunology (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain
Authors: Lu Wen, Xianlong Li, Liying Yan, Yuexi Tan, Rong Li, Yangyu Zhao, Yan Wang, Jingcheng Xie, Yan Zhang, Chunxiao Song, Miao Yu, Xiaomeng Liu, Ping Zhu, Xiaoyu Li, Yu Hou, Hongshan Guo, Xinglong Wu, Chuan He, Ruiqiang Li, Fuchou Tang, Jie Qiao
Journal: Genome biology (2014)

Abstract Background 5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate of mC demethylation and may also be a stable epigenetic modification that influences chromatin structure. hmC is particularly abundant in mammalian brains but its function is currently unknown. A high-resolution hydroxymethylome map is required to fully understand the function of hmC in the human brain. Results We present genome-wide and single-base resolution maps of hmC and mC in the human brain by combined application of Tet-assisted bisulfite sequencing and bisulfite sequencing. We demonstrate that hmCs increase markedly from the fetal to the adult stage, and in the adult brain, 13% of all CpGs are highly hydroxymethylated with strong enrichment at genic regions and distal regulatory elements. Notably, hmC peaks are identified at the 5′splicing sites at the exon-intron boundary, suggesting a mechanistic link between hmC and splicing. We report a surprising transcription-correlated hmC bias toward the sense strand and an mC bias toward the antisense strand of gene bodies. Furthermore, hmC is negatively correlated with H3K27me3-marked and H3K9me3-marked repressive genomic regions, and is more enriched at poised enhancers than active enhancers. Conclusions We provide single-base resolution hmC and mC maps in the human brain and our data imply novel roles of hmC in regulating splicing and gene expression. Hydroxymethylation is the main modification status for a large portion of CpGs situated at poised enhancers and actively transcribed regions, suggesting its roles in epigenetic tuning at these regions.
Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response.
Authors: A D Wells, H Gudmundsdottir, L A Turka
Journal: Journal of Clinical Investigation (1997)

A detailed understanding of the effects of costimulatory signals on primary T cell expansion has been limited by experimental approaches that measure the bulk response of a cell population, without distinguishing responses of individual cells. Here, we have labeled live T cells in vitro with a stable, fluorescent dye that segregates equally between daughter cells upon cell division, allowing the proliferative history of any T cell present or generated during a response to be monitored over time. This system permits simultaneous evaluation of T cell surface markers, allowing concomitant assessment of cellular activation and quantitative determination of T cell receptor (TCR) occupancy on individual cells. Through this approach, we find that TCR engagement primarily regulates the frequency of T cells that enter the proliferative pool, but has relatively little effect on the number of times these cells will ultimately divide. In contrast, CD28-costimulation regulates both the frequency of responding cells (particularly at sub-maximal levels of TCR engagement), and more prominently, the number of mitotic events that responding cells undergo. When CD28-stimulation is blocked, provision of IL-2 restores the frequency of responding cells and the normal pattern of mitotic progression, indicating that the other CD28-induced genes are not required for this effect. An unexpected finding was that even at maximal levels of TCR engagement and CD28-mediated costimulation, only 50-60% of the original T cells in culture can be induced to divide. The nondividing cells are heterogeneous for naive versus memory markers, suggesting a more complex relationship between expression of memory markers and the ability to be recruited into the dividing pool. From these studies, we conclude that a stringent checkpoint regulates the participation of activated T cells in clonal expansion, with TCR and CD28 signals having both overlapping and differential effects on the induction and maintenance of T cell responses.
Good medium-term efficacy of tocilizumab in DMARD and anti-TNF-α therapy resistant reactive amyloidosis
Authors: Markku Hakala, Kai Immonen, Markku Korpela, Mikko Vasala, Markku J Kauppi
Journal: Annals of the Rheumatic Diseases (2012)

Incidence of reactive amyloidosis associated with rheumatic diseases is markedly decreasing1 as the presence of organ failure such as end-stage renal disease.2 However, we still encounter new cases of amyloidosis. While anti-TNF-α therapy may be effective in disease modifying antirheumatic drug (DMARD) resistant cases of amyloidosis, there are yet patients whose disease does not respond to that treatment.3 ,4 

We searched for reports on tocilizumab (TCZ), an anti-interleukin-6 receptor (anti-IL-6R) antibody, as treatment for reactive amyloidosis registered in the PUBMED. Altogether six such cases were found with encouraging treatment results.3–8 All the reports are based on single case reports with limited follow-up data. We present over 1-year experience on five patients who were treated with the drug for this indication. One of the patients was included in our preliminary report of the effect of …
Confusions about colour: a classification of discolorations of the skin
Authors: J.J. Nordlund, T.F. Cestari, H. Chan, W. Westerhof
Journal: British Journal of Dermatology (2006)

Abnormal skin colour can be the result of many different factors, such as blood flow, deposition of chemicals, or alterations in morphology, within the structure of the skin. At present, however, there is no standard language, jargon, or lexicon used throughout the dermatological community to describe these abnormalities, which creates an unsound basis for education, communication and investigative and therapeutic strategies. The critical need for a precise lexicon was identified by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) who have initiated the Dermatology Lexicon Project: 'in order to create a useful, sustainable lexicon'.1 As reported in a previous paper,2 the Pigmentary Disorders Academy (PDA) – a group of dermatologists with strong interests in normal and abnormal pigmentation – has produced a consensus lexicon for skin colour, normal and abnormal, in accordance with the concepts of the NIAMS programme. The present paper builds on the previous positioning document by providing the classification of currently recognized conditions resulting in skin discoloration according to the newly specified terminology. It is intended that this new terminology should result in more astute diagnosis and decision on therapy.