tbuckley/cabot-search huggingface dataset:
Abstract 3464: The effect of EPO-receptor in estrogen receptor positive breast cancer
Authors: Marica C. Vaapil, Susann Reinbothe, Anna-Maria Larsson, Caroline Wigerup, Jianmin Sun, Annika Jögi, Drorit Neumann, Lars Rönnstrand, Sven Påhlman
Journal: Cancer Research (2014)

Abstract The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, recent clinical trials have indicated that rhEPO treatment might promote tumor progression and have a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα+) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity in ERα+ breast cancer cells and diminished ERα+ phosphorylation on Ser118, results that further support a mechanism by which EPOR affects proliferation via ERα+ mediated mechanisms. In conclusion, we show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation in ERα+ expressing breast cancer cells, in part via its capacity to positively modulate ERα activity. Citation Format: Marica C. Vaapil, Susann Reinbothe, Anna-Maria Larsson, Caroline Wigerup, Jianmin Sun, Annika Jögi, Drorit Neumann, Lars Rönnstrand, Sven Påhlman. The effect of EPO-receptor in estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3464. doi:10.1158/1538-7445.AM2014-3464
Neurodevelopmental Trajectories, Disconnection, and Schizophrenia Risk
Authors: Matcheri S. Keshavan, Tomas Paus
Journal: JAMA Psychiatry (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Head injury doubles the risk of Alzheimer's disease
Authors: Scott Gottlieb
Journal: BMJ (2000)

Young adults who experience a moderate or severe head injury have more than double the risk of developing Alzheimer's disease and other forms of dementia later in life, according to a new study.

Dr Brenda Plassman from Duke University Medical Center in Durham, North Carolina, and colleagues looked for an association between head injury and Alzheimer's disease in more than 7000 US navy or marine veterans from the second world war. In all, 548 veterans with head injury and 1228 without head injury completed all assigned stages of the study.

The researchers found that any medical history of head injury more than doubled both the risk of developing Alzheimer's disease …
Abstract 3468: Integrin-β6 is required for transforming growth factor (TGF)-β-mediated epithelial-mesenchymal transition (EMT) and promotes the disease progression of intrahepatic cholangiocellular carcinoma
Authors: Takaaki Higashi, Hiromitu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Keita Sakamoto, Hidetoshi Nitta, Akira Chikamoto, Toru Toru, Hideo Baba
Journal: Cancer Research (2014)

Abstract Background: Intrahepatic cholangiocellular carcinoma (ICC) is characterized as a poor prognostic disease represented by the highly invasiveness. Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer invasion and metastasis, and then TGF-β signaling is a potent inducible factor of EMT. Integrin-β6, which is an epithelial restricted trans-membrane protein, promotes binding to extracellular matrix proteins (fibronectin, vitronectin and tenascin) facilitating cell migration and activates TGFβ1 via binding to the latency associated peptide (LAP) of the TGF-β complex during embryogenesis and wound healing. In this study, we investigated the role of integrin-β6 during TGF-β-mediated EMT using ICC cell lines, and examined the clinic-pathological significance of Integrinβ6 expression in ICC patients. Material and Methods: We measured integrin-β6 mRNA expression by real time PCR using 7 ICC cell lines (Hucct1, HuH28, OZ, RBE, Ssp25, TFK1, Ysccc). To examine the role of integrin-β6 during TGF-β-mediated EMT in ICC cell lines, we downregulated integrin-β6 expression by RNAi during TGF-β-medaited EMT. Furthermore, using 55 resected ICC specimens, we evaluated integrin-β6 expression by immunohistochemical staining. Results: Of 7 ICC cell lines, Ysccc and OZ cell lines revealed high integrin-β6 expressions. Addition of TGF-β to Ysccc cell successfully induced EMT, characterized by the upregulated vimentin expression, downregulated E-cadherin expression, spindle-shaped morphology, and high invasiveness, with the integrin-β6 induction. The inhibition of integrin-β6 expression using RNAi abolished TGF-β-mediated EMT induction. In clinical setting, high integrin-β6 expression was significantly associated with Stage IV, lymph node metastasis, and blood vessel invasion, and then resulted in worse prognosis compared with low expression group. Conclusion : Integrin-β6 is required for TGF-β-mediated EMT and promotes the disease progression of ICC. Citation Format: Takaaki Higashi, Hiromitu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Keita Sakamoto, Hidetoshi Nitta, Akira Chikamoto, Toru Toru, Hideo Baba. Integrin-β6 is required for transforming growth factor (TGF)-β-mediated epithelial-mesenchymal transition (EMT) and promotes the disease progression of intrahepatic cholangiocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3468. doi:10.1158/1538-7445.AM2014-3468
Abstract 16921: Atrial Fibrillation is Associated with Significant Physical Function Decline in Older Adults
Authors: Jared W Magnani, Na Wang, Melissa E Garcia, Caroline L Phillips, Lisa M Sullivan, Javed Butler, Anne Newman, Emelia J Benjamin, Tamara Harris
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) is associated with significant morbidity in older adults. The effect of AF on physical function has had limited investigation. We related incident AF to prospective change in physical function across serial assessments in the Dynamics of Health, Aging, and Body Composition Study (HABC). Methods: HABC is a prospective study of older adults age 70-79 initiated in 1997-98. Physical function has been assessed in the cohort with the HABC performance battery (HABCPPB), scored 0-4, consisting of gait speed, chair stands, and balance assessments, administered at years 1, 4, 6, 8 and 10. Incident AF was ascertained from linkage with Center for Medicare and Medicaid Services, and dated by the first in-patient or second of 2 out-patient encounters. We used mixed effects regression analysis to relate incident AF to 4-year decline in the HABCPPB. Analyses incorporated age and AF as time-varying covariates and relevant multivariable adjustment (demographics; smoking, alcohol; cardiovascular disease [CVD] risk factors; prevalent CVD; and time varying hypertension, diabetes, CVD, and cancer). Results: Following exclusions, 2753 (age 73.6±2.9 years, 52% women, 41% black race) HABC participants were eligible for the analysis. We determined that older adults who developed AF at ages 74, 78, and 82 had significantly greater ( P &lt;0.001) 4-year decline in physical function than those without AF. The Figure compares the trajectories of 4-year HABCPPB decline in those with and without AF at ages 70, 74, 78, and 82. For age centered at 74, the difference in 4-year decline in HABCPPB in those with and without AF was -0.10 (95% CI -0.21, 0.00); -0.21 (-0.31, -0.11) at age 78; and -0.32 (-0.48, -0.15) at age 82. These differences in physical function decline remained significant (P&lt;0.001) following multivariable adjustment. Conclusions: In a community-dwelling cohort of older adults, AF was associated with significant 4-year decline in physical function.
Cardiovascular Health of Patients With Cancer and Cancer Survivors
Authors: Ana Barac, Gillian Murtagh, Joseph R. Carver, Ming Hui Chen, Andrew M. Freeman, Joerg Herrmann, Cezar Iliescu, Bonnie Ky, Erica L. Mayer, Tochi M. Okwuosa, Juan Carlos Plana, Thomas D. Ryan, Anne K. Rzeszut, Pamela S. Douglas
Journal: Journal of the American College of Cardiology (2015)
Zygote and “Clonote” — The Ethical Use of Embryonic Stem Cells
Authors: Paul R McHugh
Journal: New England Journal of Medicine (2004)

The Stem-Cell DebateBioethics is a debate without rules about a future dimly apprehended — a debate that is ever in danger of slipping from judicious deliberations into secular sermons. I awoke to these facts soon after I had joined the President's Council on Bioethics, when we began to discuss embryonic stem cells. The discovery of pluripotential, infinitely self-replicating stem cells early in the 1980s had lit up a whole domain of cellular and developmental biology and suggested therapeutic approaches to chronic, debilitating, and incurable diseases such as Parkinson's disease and diabetes mellitus. But for some years, the U.S. government, . . .
Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease
Authors: A. Petit, O.E. Dadzie
Journal: British Journal of Dermatology (2013)

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research.
Genome Organization of the SARS-CoV
Authors: Jing Xu, Jianfei Hu, Jing Wang, Yujun Han, Yongwu Hu, Jie Wen, Yan Li, Jia Ji, Jia Ye, Zizhang Zhang, Wei Wei, Songgang Li, Jun Wang, Jian Wang, Jun Yu, Huanming Yang
Journal: Genomics Proteomics & Bioinformatics (2003)

Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.
LATE RECRUDESCENCE IN ENCEPHALITIS LETHARGICA WITH SUCCESSION OF NEW MANIFESTATIONS AT INTERVALS OF YEARS; THE PROBLEM OF PROGNOSIS
Authors: Alfred Gordon
Journal: Annals of Internal Medicine (1936)

Article1 June 1936LATE RECRUDESCENCE IN ENCEPHALITIS LETHARGICA WITH SUCCESSION OF NEW MANIFESTATIONS AT INTERVALS OF YEARS; THE PROBLEM OF PROGNOSISALFRED GORDON, F.A.C.P.ALFRED GORDON, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-12-1725 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is pretty well established that the virus of encephalitis lethargica may invade any area of the central nervous system but has a special affinity for the striatal region in the mid-brain. The Parkinsonian symptom-group is the usual clinical expression of this localization. As to the so-called sequelae, the literature shows a multiplicity of phenomena. The sensory system, the special sense organs, the motor system, the vegetative nervous system, the psychic functions—all may show morbid alterations. Some of these various manifestations are rare or very rare, while others are common. Hyperkinetic phenomena are the most frequent. Since, in some cases,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Received for publication September 27, 1935.Patients presented before the Philadelphia Neurological Society. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1936Volume 9, Issue 12Page: 1725-1728KeywordsAutonomic nervous systemCentral nervous systemEncephalitisMotor system ePublished: 1 December 2008 Issue Published: 1 June 1936 PDF downloadLoading ...
The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8
Authors: Susanna Ranta, Yonghui Zhang, Barbara Ross, Liina Lonka, Elina Takkunen, Anne Messer, Julie Sharp, Ruth Wheeler, Kenro Kusumi, Sara Mole, Wencheng Liu, Marcelo Bento Soares, Maria de Fatima Bonaldo, Aune Hirvasniemi, Albert de la Chapelle, T. Conrad Gilliam, Anna-Elina Lehesjoki
Journal: Nature Genetics (1999)
Abstract 18910: Angiotensin Converting Enzyme 2 Deficiency Results in Cardiac Insulin Resistance in Response to High-Fat Diet
Authors: Vaibhav B Patel, Jun Mori, Brent A McLean, Gary D Lopaschuk, Gavin Y Oudit
Journal: Circulation (2014)

Background: Activation of the renin-angiotensin system (RAS) can alter the cardiac energy substrate preference, thereby contributing to the progression of heart failure. Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the RAS where it metabolizes angiotensin (Ang) II into Ang (1-7). Hypothesis: Myocardial ACE2 was upregulated in response to high-fat diet in wildtype (WT) mice. We hypothesize that ACE2 upregulation is a compensatory response and loss of ACE2 will worsened obesity and its associated cardiomyopathy. Methods and Results: ACE2-null (ACE2-/y; ACE2KO) and WT litter-mate control mice were fed with high-fat diet (HFD; 45 kcal%) or control diet (10 kcal%) and studied at 6-months of age. In contrast to our hypothesis, loss of ACE2 resulted in decreased obesity in response to HFD compared to WT mice (body weight at 6-months: 45.9±4.3 in ACE2KO-HFD vs 51.4±1.55 in WT-HFD; p&lt;0.05). Conversely, ACE2KO-HFD mice showed increased fasting plasma glucose levels (6.76±0.7 in ACE2KO-HFD vs 5.11±0.6 in WT-HFD; p&lt;0.05) with worsened whole-body insulin resistance. We subjected hearts to ex vivo aerobic perfusions to measure cardiac energy metabolism. ACE2KO-HFD hearts showed markedly decreased cardiac work along with reduced insulin response suggesting increased myocardial insulin resistance. ACE2KO-HFD hearts relied predominantly on fat metabolism as the energy source, a feature observed in cardiomyopathy. Pressure-volume analysis showed worsened diastolic dysfunction in the ACE2KO hearts compared to WT hearts in response to HFD, which was primarily due to impaired active relaxation (Tau(Weiss): 7.41±0.4 in ACE2KO-HFD vs 6.26±0.52 in WT-HFD; p&lt;0.05). Metabolic and functional changes in the ACE2KO-HFD were associated with impaired insulin signaling (decreased p-Akt) and decreased phosphorylation of AMPK. ACE2KO-HFD hearts also showed increased pyruvate dehydrogenase kinase 4 expression and phosphorylation of pyruvate dehydrogenase. Conclusions: Renin-angiotensin system plays an important role in cardiac metabolism. We found a novel role of ACE2 in cardiac insulin signaling, where ACE2 negatively regulates obesity and hyperglycemia induced cardiac insulin-resistance and alterations in cardiac metabolism.
My most unfortunate mistake: Always double check
Authors: L. Bradley
Journal: BMJ (2000)

The attitudes of the professionals were more unexpected.Guided self management plans were seen as a low priority, and most patients were managed by monitoring or policing.Education appeared to mean, at the most basic level, ensuring that the correct drug was taken at the right time in the most effective way.Our findings suggest that attempts to introduce guided self management plans in primary care are unlikely to be successful.If guided self management is to work, new plans that are more patient centred need to be developed in place of those based on the medical model.Nurses need to be not only helped and supported by general practitioners but trained in techniques that enable changes in patient behaviour. 13In addition, we need to identify which patients need or are likely to accept guided self management.We thank the general practitioners, asthma nurses, and patients who volunteered to take part in this study.
Roadblocks to caspase-dependent cell death in cancer: Therapeutic strategies.
Authors: John C. Reed
Journal: Cancer Research (2006)

SY11-02   Bone marrow (BM)-derived cells regulate key processes in tumor development, such as the angiogenic switch, immune escape, and metastasis. Both BM-derived hematopoietic cells (HCs) and endothelial progenitor cells (EPCs) have been shown to contribute to tumor vascularization. This scenario has attracted great interest because these cells may represent novel targets for therapeutic interventions, and ideal vehicles for selective gene delivery to tumors. We have recently shown that a subset of BM-derived monocytes characterized by the expression of the Tie2 receptor (designated as TEMs for Tie2-Expressing Mononuclear cells) specifically homed to sites of angiogenesis in mice, including tumors. Although TEMs expressed some endothelial cell (EC) markers, they did not differentiate into ECs in tumors. By using lentiviral vector (LV)-mediated transgenesis, we generated mice expressing GFP under the control of the Tie2 gene transcription regulatory sequences. By using this mouse model, we phenotypically characterized the TEMs, tracked their origin from the BM, and isolated them from peripheral blood (PB) and tumors to study their function. We demonstrated that TEMs represent a distinct lineage of pro-angiogenic monocytes phenotypically and functionally determined in the circulation, and we are currently performing a transcriptional profile study by comparing TEMs with other tumor-infiltrating hematopoietic subsets. Remarkably, in different experimental models, TEMs isolated from PB or tumor samples had superior efficacy in promoting angiogenesis as compared to other circulating or tumor-infiltrating myeloid cells. By using a Tie2 promoter-driven thymidine kinase (tk) transgene and LV-mediated transgenesis, we generated transgenic mice that display a conditional angiogenesis-defective phenotype and dramatic tumor resistance. By using these mice and different transplantation strategies, we found that TEMs, and not EPCs, accounted for the major contribution of BM-derived cells to tumor angiogenesis. We proved the relevance of our findings in stringent models of oncogenesis, including human orthotopic brain and spontaneous pancreatic tumors. Remarkably, the selective elimination of TEMs completely prevented human glioma neovascularization in the mouse brain and induced substantial tumor regression. Our findings support the emerging paradigm that BM-derived cells recruited to tumors, rather than providing building blocks for postnatal vasculogenesis, comprise a functionally distinct myeloid lineage of paracrine inducers of angiogenesis. We are currently exploring the possibility of targeting anti-angiogenic drugs to tumors by using TEMs as gene therapy vehicles. Preliminary studies indicate that potent anti-tumor and/or anti-angiogenic molecules can be delivered to tumors via TEMs in the setting of a BM transplant, in the absence of systemic toxicity. Anti-tumor efficacy studies are ongoing and will be presented at the meeting.
Richter's transformation to diffuse large B‐cell lymphoma: A retrospective study reporting clinical data, outcome, and the benefit of adding rituximab to chemotherapy, from the <scp>I</scp>sraeli <scp>CLL</scp><scp>S</scp>tudy <scp>G</scp>roup
Authors: Tamar Tadmor, Lev Shvidel, Osnat Bairey, Neta Goldschmidt, Rosa Ruchlemer, Riva Fineman, Naomi Rahimi‐Levene, Yair Herishanu, Mona Yuklea, Ariela Arad, Ariel Aviv, Aaron Polliack
Journal: American Journal of Hematology (2014)

Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre‐existing chronic lymphocytic leukemia (CLL). Data on RS is sparse and mostly derived from case reports or small series of patients and only a few larger cohorts have been published. The purpose of this large retrospective study was to summarize our national experience with RS in CLL, examine possible risk factors, and analyze relevant demographic, laboratory and clinical parameters, including results of therapy and outcome. We first evaluated data obtained from 119 patients with RS diagnosed during 1971–2010 from 12 medical centers in Israel. The final cohort summarized consisted of 81 patients with RS who developed only diffuse large B‐cell lymphoma (DLBCL) after exclusion all cases with insufficient data and those who were not DLBCL. Median overall survival from time of diagnosis of RS was 8 months; after applying the Richter score, patients could be stratified into three prognostic groups, while all other clinical and laboratory parameters evaluated had no prognostic significance. Prior therapy for CLL had no impact on RS survival ( P = 0.8) and patients with therapy “naïve” RS and those who had already received chemotherapy prior to developing RS, had the same survival. The addition of rituximab to chemotherapy for RS improved 2 years overall survival from 19% in the chemotherapy alone arm to 42% ( P value of 0.001). Although prognosis of patients with RS remains dismal, this retrospective observation provides support for the use of chemo‐immunotherapy in DLBCL‐RS. Am. J. Hematol. 89:E218–E222, 2014. © 2014 Wiley Periodicals, Inc.