tbuckley/cabot-search huggingface dataset:
p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells
Authors: Carmela Ciccarelli, Francesco Marampon, Arianna Scoglio, Annunziata Mauro, Cristina Giacinti, Paola De Cesaris, Bianca M Zani
Journal: Molecular Cancer (2005)

Abstract Background p21 WAF1 , implicated in the cell cycle control of both normal and malignant cells, can be induced by p53-dependent and independent mechanisms. In some cells, MEKs/ERKs regulate p21 WAF1 transcriptionally, while in others they also affect the post-transcriptional processes. In myogenic differentiation, p21 WAF1 expression is also controlled by the myogenic transcription factor MyoD. We have previously demonstrated that the embryonal rhabdomyosarcoma cell line undergoes growth arrest and myogenic differentiation following treatments with TPA and the MEK inhibitor U0126, which respectively activate and inhibit the ERK pathway. In this paper we attempt to clarify the mechanism of ERK-mediated and ERK-independent growth arrest and myogenic differentiation of embryonal and alveolar rhabdomyosarcoma cell lines, particularly as regards the expression of the cell cycle inhibitor p21 WAF1 . Results p21 WAF1 expression and growth arrest are induced in both embryonal (RD) and alveolar (RH30) rhabdomyosarcoma cell lines following TPA or MEK/ERK inhibitor (U0126) treatments, whereas myogenic differentiation is induced in RD cells alone. Furthermore, the TPA-mediated post-transcriptional mechanism of p21 WAF1 -enhanced expression in RD cells is due to activation of the MEK/ERK pathway, as shown by transfections with constitutively active MEK1 or MEK2, which induces p21 WAF1 expression, and with ERK1 and ERK2 siRNA, which prevents p21 WAF1 expression. By contrast, U0126-mediated p21 WAF1 expression is controlled transcriptionally by the p38 pathway. Similarly, myogenin and MyoD expression is induced both by U0126 and TPA and is prevented by p38 inhibition. Although MyoD and myogenin depletion by siRNA prevents U0126-mediated p21 WAF1 expression, the over-expression of these two transcription factors is insufficient to induce p21 WAF1 . These data suggest that the transcriptional mechanism of p21 WAF1 expression in RD cells is rescued when MEK/ERK inhibition relieves the functions of myogenic transcription factors. Notably, the forced expression of p21 WAF1 in RD cells causes growth arrest and the reversion of anchorage-independent growth. Conclusion Our data provide evidence of the key role played by the MEK/ERK pathway in the growth arrest of Rhabdomyosarcoma cells. The results of this study suggest that the targeting of MEK/ERKs to rescue p21 WAF1 expression and myogenic transcription factor functions leads to the reversal of the Rhabdomyosarcoma phenotype.
Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms
Authors: Wenru Su, Qian Wan, Jingwen Huang, Longhui Han, Xiaoqing Chen, Guihua Chen, Nancy Olsen, Song Guo Zheng, Dan Liang
Journal: Journal of Allergy and Clinical Immunology (2015)
Matrix as an Interstitial Transport System
Authors: Dong Fan, Esther E. Creemers, Zamaneh Kassiri
Journal: Circulation Research (2014)

The extracellular matrix (ECM) is best known for its function as a structural scaffold for the tissue and more recently as a microenvironment to sequester growth factors and cytokines allowing for rapid and localized changes in their activity in the absence of new protein synthesis. In this review, we explore this and additional new aspects of ECM function in mediating cell-to-cell communications. Fibrillar and nonfibrillar components of ECM can limit and facilitate the transport of molecules through the extracellular space while also regulating interstitial hydrostatic pressure. In turn, transmembrane communications via molecules, such as ECM metalloproteinase inducer, thrombospondins, and integrins, can further mediate cell response to extracellular cues and affect ECM composition and tissue remodeling. Other means of cell-to-cell communication include extracellular microRNA transport and its contribution to gene expression in target cells and the nanotube formation between distant cells, which has recently emerged as a novel conduit for intercellular organelle sharing thereby influencing cell survival and function. The information summarized and discussed here are not limited to the cardiovascular ECM but encompass ECM in general with specific references to the cardiovascular system.
Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation
Authors: Ichiro Hanamura, James P. Stewart, Yongsheng Huang, Fenghuang Zhan, Madhumita Santra, Jeffrey R. Sawyer, Klaus Hollmig, Maurizio Zangarri, Mauricio Pineda-Roman, Frits van Rhee, Federica Cavallo, Bart Burington, John Crowley, Guido Tricot, Bart Barlogie, John D. Shaughnessy
Journal: Blood (2006)
Revision of a Non United Subtrochanteric Femoral Fracture Around a Failed Intramedullary Nail With the Use of Ria Products, Bmp-7 and Hydoxyapatite
Authors: C. Tzioupis, P. Panteliadis, Z. Gamie, A. Leonidou, S. Graham, E. Tsiridis
Journal: International Journal of Surgery (2010)
GPs worried about having to change to new untested software systems
Authors: Rebecca Coombes
Journal: BMJ (2004)

By 2010, every patient in England should have an individual electronic NHS care record.

In essence, this refers to a computer file that includes general practice and hospital records, detailing key treatments and care.

The 10 year contract to set up and run the NHS Care Records Service (NHS CRS) was awarded to BT in December 2003 and is worth £620m ($1.1bn; 932m).

The service will connect more than 30 000 GPs and 270 acute, community, and mental health NHS trusts in a single system.

Although much of the work is being developed nationally there are important local variations. BT will be the national application …
Immunofluorescence studies in recent myocardial infarction
Authors: J. Kuch, T. Chorzelski
Journal: Cardiovascular Research (1971)

Journal Article Immunofluorescence studies in recent myocardial infarction Get access Jerzy Kuch, Jerzy Kuch From the Institute of Cardiology and Department of Dermatology, School of Medicine, Warsaw Search for other works by this author on: Oxford Academic PubMed Google Scholar Tadeusz Chorzelski Tadeusz Chorzelski From the Institute of Cardiology and Department of Dermatology, School of Medicine, Warsaw Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 3, July 1971, Pages 353–355, https://doi.org/10.1093/cvr/5.3.353 Published: 01 July 1971
Intrinsic B cell defects in NZB and NZW mice contribute to systemic lupus erythematosus in (NZB x NZW)F1 mice.
Authors: L Reininger, T H Winkler, C P Kalberer, M Jourdan, F Melchers, A G Rolink
Journal: The Journal of Experimental Medicine (1996)

We have previously shown that long-term in vitro proliferating fetal liver pre-B cell lines derived from autoimmune-prone (NZB x NZW)F1 (BW) mice, but not normal (B6 x DBA2)F1 mice, can differentiate in severe combined immunodeficient (SCID) mice to produce elevated levels of serum immunoglobulin (Ig) M and IgG, and high titers of antinuclear antibodies The contribution of parental NZB and NZW strains to B cell abnormalities of BW hybrid mice was investigated here by preparing pre-B cells and transferring them into immunodeficient SCID- and RAG-2-targeted mice. We show that transfer of NZB pre-B cells led to a marked IgM hypergammaglobulinemia and to the production of limited amounts of IgG2a. On the other hand, the transfer of NZW pre-B cell lines led to moderately elevated IgM levels and marked hypergammaglobulinemia of IgG2a. High IgM and low IgG anti-DNA titers are found in the recipients of NZB pre-B cells, whereas those receiving NZW pre-B cells contained lower levels of IgM and high titers of IgG anti-DNA. In marked contrast, essentially identical titers of antibodies directed against a non-self-antigen, DNP, are found in all group of pre-B cell recipients. Thus, B-lineage cells of both NZB and NZW parental strains manifest abnormalities associated with the development of this lupus-like disease. Therefore, the present study strongly suggests a complex inheritance of B cell abnormalities in autoimmune-prone (NZB x NZW)F1 mice and emphasizes the critical importance of intrinsic B cell defects in the development of murine systemic lupus erythematosus.
COPD among non-smokers
Authors: Stig Hagstad, Linda Ekerljung, Anne Lindberg, Eva Rönnmark, Bo Lundbäck
Journal: European Respiratory Journal (2011)

Background: In westernized countries including Sweden, smoking and increasing age are the most important risk factors for COPD. Prevalence and risk factors of COPD among non-smokers are not well studied.

Aim: To study the prevalence and risk factors of COPD among never smokers and to determine the proportion of never smokers among subjects with COPD.

Methods: Of 5189 postal questionnaire responders (response rate 88%) aged 46-77 years from a stratified sample of the general population of Norrbotten, Sweden, a random sample of 1500 subjects were invited to structured interviews and lung functions test, and 1237 completed a lung function test with acceptable quality. Never smokers were defined as those who had smoked <1 cigarette/day for <1 year. COPD was defined as GOLD stage ≥II, as several medical conditions are associated with a FEV1/FVC <0.7.

Results: The prevalence of COPD among non-smokers was 3.4% and tended to be more common among women than men (4% vs 2.3%, NS) and was strongly age related particularly among men. For comparison the overall prevalence in ages >45 y COPD was 8.1% (similar in men and women). Among never smokers the prevalence of severe COPD (FEV1<50% of predicted) was 0.8 (women 0.9%; men 0.6%; NS). In contrast to men, severe cases of COPD were found among women aged <65 years. Of all men with COPD, 15% were never smokers versus twice that much among women. Increasing age was a significant risk factor, while passive smoking, manual work in industry and female sex tended to be associated with COPD among never smokers.

Conclusion: The prevalence of clinically relevant COPD among never smokers aged >45 y was 3.4% and was associated with increasing age. One out of seven men with COPD versus one out of three women had never been smokers.
Endothelial/Pericyte Interactions
Authors: Annika Armulik, Alexandra Abramsson, Christer Betsholtz
Journal: Circulation Research (2005)

Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in the blood vessel wall have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function. Failure of the interactions between the 2 cell types, as seen in numerous genetic mouse models, results in severe and often lethal cardiovascular defects. Abnormal interactions between the 2 cell types are also implicated in a number of human pathological conditions, including tumor angiogenesis, diabetic microangiopathy, ectopic tissue calcification, and stroke and dementia syndrome CADASIL. In the present review, we summarize current knowledge concerning the identity, characteristics, diversity, ontogeny, and plasticity of pericytes. We focus on the advancement in recent years of the understanding of intercellular communication between endothelial and mural cells with a focus on transforming growth factor beta, angiopoietins, platelet-derived growth factor, spingosine-1-phosphate, and Notch ligands and their respective receptors. We finally highlight recent important data contributing to the understanding of the role of pericytes in tumor angiogenesis, diabetic retinopathy, and hereditary lymphedema.
Outcome for Cancer Patients Requiring Mechanical Ventilation
Authors: Jeffrey S. Groeger, Peter White, David M. Nierman, Jill Glassman, Weiji Shi, David Horak, Kristen Price
Journal: Journal of Clinical Oncology (1999)

To describe hospital survival for cancer patients who require mechanical ventilation.A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired.Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52.This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted.
Reduced Antibody Responses to Vaccinations in Children Exposed to Polychlorinated Biphenyls
Authors: Carsten Heilmann, Philippe Grandjean, Pál Weihe, Flemming Nielsen, Esben Budtz-Jørgensen
Journal: PLoS Medicine (2006)

Background Developmental exposure to polychlorinated biphenyls (PCBs) has been implicated as a possible cause of deficient immune function in children. This study was designed to assess whether prenatal and postnatal exposure to PCBs impacts on antibody response to childhood immunizations. Methods and Findings Two birth cohorts were formed in the Faroe Islands, where exposures vary widely, because traditional diets may include whale blubber contaminated with PCBs. Prenatal exposure was determined from maternal concentrations of PCBs in pregnancy serum and milk. Following routine childhood vaccinations against tetanus and diphtheria, 119 children were examined at 18 mo and 129 children at 7 y of age, and their serum samples were analyzed for tetanus and diphtheria toxoid antibodies and for PCBs. The antibody response to diphtheria toxoid decreased at age 18 mo by 24.4% (95% confidence interval [CI], 1.63–41.9; p = 0.04) for each doubling of the cumulative PCB exposure at the time of examination. The diphtheria response was lower at age 7 y and was not associated with the exposure. However, the tetanus toxoid antibody response was affected mainly at age 7 y, decreasing by 16.5% (95% CI, 1.51–29.3; p = 0.03) for each doubling of the prenatal exposure. Structural equation analysis showed that the early postnatal exposure was the most important predictor of a decreased vaccination response. Conclusions Increased perinatal exposure to PCBs may adversely impact on immune responses to childhood vaccinations. The clinical implications of insufficient antibody production emphasize the need for prevention of immunotoxicant exposures.
Nuclear and cytoplasmic dynamics of sperm penetration, pronuclear formation and microtubule organization during fertilization and early preimplantation development in the human
Authors: Jonathan Van Blerkom, Patrick Davis, John Merriam, Jane Sinclair
Journal: Human Reproduction Update (1995)

Abstract This report describes spatial and temporal aspects of sperm penetration and intracytoplasmic migration, pronuclear evolution and the specificity of presyngamic opposition, stage-specific changes in cytoskeletal organization and the relative contribution of maternal and paternal components to mitotic spindle formation. These studies involved observations of living human oocytes during conventional insemination in vitro and after intracytoplasmic deposition of spermatozoa, analysis of chromatin organization and distribution during pronuclear evolution, and detection of actin and α-, rβ- and γ-tubulin by confocal immuno-fluorescence microscopy. Immature and mature oocytes, penetrated but unfertilized oocytes, fertilized but arrested eggs, and cleavage-stage embryos from normal and dispermic fertilizations were examined. The results demonstrate that sperm nuclear migration to the maternal perinuclear region is rapid and linear, occurs in the absence of a detectable cytoskeletal system and appears to be assisted by an unusual configuration of the sperm tail principal piece which results from either retained intracytoplasmic motility or the process by which the sperm tail is progressively incorporated into the oocyte. Our findings also show a specificity of pronuclear alignment that is associated with a polarized distribution of both maternal and paternal chromatin, and with the position of the sperm centrosome and the presence of microtubules nucleated from this structure. The results also indicate that a maternal microtubule nucleating capacity is present in the immature oocyte but is apparently inactive until spindle formation. The poles of the first mitotic spindle appear to be derived from the sperm centrosome, although some maternal contribution cannot be excluded. The sperm tail and centrosome persist in a single cell through the cleavage stages, and the latter serves as a prominent site of cytoplasmic microtubule nucleation. The results provide a detailed understanding of the cellular and nuclear morphodynamics of the human fertilization process and indicate subtle defects that may be responsible for early developmental failure.
Resting energy expenditure, body composition, and excess weight in the obese
Authors: Gary D. Foster, Thomas A. Wadden, James L. Mullen, Albert J. Stunkard, Jack Wang, Irene D. Feurer, Richard N. Pierson, Mei U. Yang, Elio Presta, Theodore B. Van Itallie, Paul S. Lemberg, Jeffery Gold
Journal: Metabolism (1988)
Nicotine Dependence: Biology, Behavior, and Treatment
Authors: Riju Ray, Robert A. Schnoll, Caryn Lerman
Journal: Annual Review of Medicine (2009)

Despite great advances in the understanding and treatment of nicotine dependence, close to 21% of adults in the United States continue to smoke. Tobacco use is the single greatest cause of premature and preventable death in the United States. This article reviews the epidemiology, assessment, neurobiology, genetic etiology, and treatment of nicotine dependence. Enhanced understanding of these dimensions of nicotine dependence may help to advance progress toward lowering the prevalence rate of tobacco use in the U.S. and lowering the rate of tobacco-related morbidity and mortality.
Endothelial Nitric Oxide Synthase Mediates Lymphangiogenesis and Lymphatic Metastasis
Authors: Johanna Lahdenranta, Jeroen Hagendoorn, Timothy P. Padera, Tohru Hoshida, Gregory Nelson, Satoshi Kashiwagi, Rakesh K. Jain, Dai Fukumura
Journal: Cancer Research (2009)

Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vascular endothelial growth factor (VEGF)-C and VEGF-D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NO synthase (NOS) expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and VEGF receptor-3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose-dependent manner. We find that an NOS inhibitor, L-NMMA, blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C-induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system.
Familial Sudden Death Is an Important Risk Factor for Primary Ventricular Fibrillation
Authors: Lukas R.C. Dekker, Connie R. Bezzina, José P.S. Henriques, Michael W. Tanck, Karel T. Koch, Marco W. Alings, Alfred E.R. Arnold, Menko-Jan de Boer, Anton P.M. Gorgels, H. Rolf Michels, Agnes Verkerk, Freek W.A. Verheugt, Felix Zijlstra, Arthur A.M. Wilde
Journal: Circulation (2006)

Primary ventricular fibrillation (VF) accounts for the majority of deaths during the acute phase of myocardial infarction. Identification of patients at risk for primary VF remains very poor.We performed a case-control study in patients with a first ST-elevation myocardial infarction (STEMI) to identify independent risk factors for primary VF. A total of 330 primary VF survivors (cases) and 372 controls were included; patients with earlier infarcts or signs of structural heart disease were excluded. Baseline characteristics, including age, gender, drug use, and ECG parameters registered well before the index infarction, as well as medical history, were not different. Infarct size and location, culprit coronary artery, and presence of multivessel disease were similar between groups. Analysis of ECGs performed at hospital admission for the index STEMI revealed that cumulative ST deviation was significantly higher among cases (OR per 10-mm ST deviation 1.59, 95% CI 1.25 to 2.02). Analysis of medical histories among parents and siblings showed that the prevalence of cardiovascular disease was similar between cases and controls (73.1% and 73.0%, respectively); however, familial sudden death occurred significantly more frequently among cases than controls (43.1% and 25.1%, respectively; OR 2.72, 95% CI 1.84 to 4.03).In a population of STEMI patients, the risk of primary VF is determined by cumulative ST deviation and family history of sudden death.
External validation of nomogram for the prediction of recurrence after curative resection in early gastric cancer
Authors: J.H. Kim, H.S. Kim, W.Y. Seo, C.M. Nam, K.Y. Kim, H.C. Jeung, J.F. Lai, H.C. Chung, S.H. Noh, S.Y. Rha
Journal: Annals of Oncology (2011)