tbuckley/cabot-search huggingface dataset:
TCRζdimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues
Authors: Zhuoli Zhang, Claire L. Gorman, Anna-Chiara Vermi, Claudia Monaco, Andrew Foey, Sally Owen, Parisa Amjadi, Alena Vallance, Catherine McClinton, Federica Marelli-Berg, Pia Isomäki, Andrew Russell, Francesco Dazzi, Timothy J. Vyse, Fionula M. Brennan, Andrew P. Cope
Journal: Blood (2007)

Abstract The T-cell receptor ζ (TCRζ) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRζ expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRζ expression and effector function in T cells. We report here that TCRζdim lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRζbright counterparts, TCRζdim cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRζdim T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRζdim T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRζdim T cells make them promising cellular targets for the treatment of chronic inflammatory disease.
Utility of a New Procedure for Diagnosing Mental Disorders in Primary Care
Authors: Robert L. Spitzer
Journal: JAMA (1994)

<h3>Objective.</h3> —To assess the validity and utility of PRIME-MD (Primary Care Evaluation of Mental Disorders), a new rapid procedure for diagnosing mental disorders by primary care physicians. <h3>Design.</h3> —Survey; criterion standard. <h3>Setting.</h3> —Four primary care clinics. <h3>Subjects.</h3> —A total of 1000 adult patients (369 selected by convenience and 631 selected by site-specific methods to avoid sampling bias) assessed by 31 primary care physicians. <h3>Main Outcome Measures.</h3> —PRIME-MD diagnoses, independent diagnoses made by mental health professionals, functional status measures (Short-Form General Health Survey), disability days, health care utilization, and treatment/ referral decisions. <h3>Results.</h3> —Twenty-six percent of the patients had a PRIME-MD diagnosis that met full criteria for a specific disorder according to the<i>Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition</i>. The average time required of the primary care physician to complete the PRIME-MD evaluation was 8.4 minutes. There was good agreement between PRIME-MD diagnoses and those of independent mental health professionals (for the diagnosis of any PRIME-MD disorder, κ=0.71; overall accuracy rate=88%). Patients with PRIME-MD diagnoses had lower functioning, more disability days, and higher rates of health care utilization than did patients without PRIME-MD diagnoses (for all measures,<i>P</i>&lt;.005). Nearly half (48%) of 287 patients with a PRIME-MD diagnosis who were somewhat or fairly well-known to their physicians had not been recognized to have that diagnosis before the PRIME-MD evaluation. A new treatment or referral was initiated for 62% of the 125 patients with a PRIME-MD diagnosis who were not already being treated. <h3>Conclusion.</h3> —PRIME-MD appears to be a useful tool for identifying mental disorders in primary care practice and research. (<i>JAMA</i>. 1994;272:1749-1756)
A pharmacogenetic analysis of the Canadian Cancer Trials Group MY.10 clinical trial of maintenance therapy for multiple myeloma
Authors: Ming Han, Alli Murugesan, Nizar J. Bahlis, Kevin Song, Darrell White, Christine Chen, Matthew D. Seftel, Kang Howsen-Jan, Donna Reece, Keith Stewart, Yagang Xie, Annette E. Hay, Lois Shepherd, Marina Djurfeldt, Liting Zhu, Ralph M. Meyer, Bingshu E. Chen, Tony Reiman
Journal: Blood (2016)
Smoking Patterns and Epidemiology of Lung Cancer in the United States: Are They Compatible?
Authors: William Haenszel, Michael B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1956)

Smoking Patterns and Epidemiology of Lung Cancer in the United States: Are They Compatible? Get access William Haenszel, William Haenszel Biometry and Epidemiology Branch, National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin Michael B. Shimkin Biometry and Epidemiology Branch, National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 6, June 1956, Pages 1417–1441, https://doi.org/10.1093/jnci/16.6.1417 Published: 01 June 1956 Article history Received: 21 December 1955 Published: 01 June 1956
The Impact of Immunophenotypic Subtypes and Treatment Regimens on Patient Outcomes in Monomorphic Post-Transplant Lymphoproliferative Disorders (Diffuse Large B-Cell Lymphoma)
Authors: Dejan Radeski, Daniela Hoehn, Francesca Montanari, Bachir Alobeid, Yuan Zhang, Jennifer E Amengual, Ahmed Sawas, Changchun Deng, Owen A. O'Connor, Govind Bhagat
Journal: Blood (2014)
Role of interleukin-1 receptor 1/MyD88 signalling in the development and progression of pulmonary hypertension
Authors: Aurélien Parpaleix, Valérie Amsellem, Amal Houssaini, Shariq Abid, Marielle Breau, Elisabeth Marcos, Daigo Sawaki, Marion Delcroix, Rozenn Quarck, Aurélie Maillard, Isabelle Couillin, Bernhard Ryffel, Serge Adnot
Journal: European Respiratory Journal (2016)

Pulmonary artery smooth muscle cell (PA-SMC) proliferation and inflammation are key components of pulmonary arterial hypertension (PAH). Interleukin (IL)-1β binds to IL-1 receptor (R)1, thereby recruiting the molecular adaptor myeloid differentiation primary response protein 88 (MyD88) (involved in IL-1R1 and Toll-like receptor signal transduction) and inducing IL-1, IL-6 and tumour necrosis factor-α synthesis through nuclear factor-κB activation. We investigated the IL-1R1/MyD88 pathway in the pathogenesis of pulmonary hypertension. Marked IL-1R1 and MyD88 expression with predominant PA-SMC immunostaining was found in lungs from patients with idiopathic PAH, mice with hypoxia-induced pulmonary hypertension and SM22-5-HTT + mice. Elevations in lung IL-1β, IL-1R1, MyD88 and IL-6 preceded pulmonary hypertension in hypoxic mice. IL-1R1 −/− , MyD88 −/− and control mice given the IL-1R1 antagonist anakinra were protected similarly against hypoxic pulmonary hypertension and perivascular macrophage recruitment. Anakinra reversed pulmonary hypertension partially in SM22-5-HTT + mice and markedly in monocrotaline-treated rats. IL-1β-mediated stimulation of mouse PA-SMC growth was abolished by anakinra and absent in IL-1R1 −/− and MyD88 −/− mice. Gene deletion confined to the myeloid lineage (M.lys-Cre MyD88 fl/fl mice) decreased pulmonary hypertension severity versus controls, suggesting IL-1β-mediated effects on PA-SMCs and macrophages. The growth-promoting effect of media conditioned by M1 or M2 macrophages from M.lys-Cre MyD88 fl/fl mice was attenuated. Pulmonary vessel remodelling and inflammation during pulmonary hypertension require IL-1R1/MyD88 signalling. Targeting the IL-1β/IL-1R1 pathway may hold promise for treating human PAH.
Nonmechanical factors affecting aortocoronary vein graft flow.
Authors: Tyers Gf, O'Neill Mj, Messner Jt, Waldhausen Ja
Journal: Circulation (1975)

To study aortocoronary vein graft flow, hemodynamic measurements were made in 17 patients with 22 grafts while on cardiopulmonary bypass during ventricular fibrillation and sinus rhythm and 15 minutes after termination of cardiopulmonary bypass. When compared with graft flow to the stable working heart, flow to the nonworking heart in sinus rhythm was reduced 50%. When fibrillating, the nonworking heart received 33% more flow than when in sinus rhythm but still significantly less flow than the working heart. All hemodynamic parameters measured, including flow in 12 grafts, remained stable between 15 minutes and 60 minutes following cardiopulmonary bypass. In contrast, heart rate and flow in 10 grafts fell within five minutes after 1 mg of propranolol was given intravenously. Although it was still reduced, heart rate had begun to rise 30 minutes after propranolol, but graft flow did not begin to return toward predrug control levels until over 60 minutes after drug administration. Further reduction in aortocoronary vein graft flow after heart rate had started to increase supports the possibility of a direct propranolol action reducing myocardial oxygen consumption in addition to its bradycardiac effect. This study shows the sensitivity of intraoperative vein graft flow to physiological and pharmacological factors and the need to standardize the technique and timing of flow measurements if their value for predicting long-term graft patency is to be determined.
Chronic Nonbacterial Osteomyelitis With FDG Avid Rib Destruction and Extensive Lymphadenopathy
Authors: Yiyan Liu
Journal: Clinical Nuclear Medicine (2016)

Chronic nonbacterial osteomyelitis is a rare entity of unknown etiology and most likely an autoinflammatory disease. A 45-year-old man complained of a growing painful mass of the right chest wall. FDG PET/CT demonstrated a large destructive rib lesion with intense uptake and extensive FDG avid lymphadenopathy, which mimicked a malignant or metastatic disease. Both CT guided core-needle and excisional biopsies showed reactive/regenerative/granulomatous changes coupled with focal neutrophils and marrow atrophy, consistent with chronic osteomyelitis. Stains and cultures of surgical and wound specimens and multiple blood cultures were all negative for any kind of microorganism.
Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis
Authors: Laia Bruni, Mireia Diaz, Leslie Barrionuevo-Rosas, Rolando Herrero, Freddie Bray, F Xavier Bosch, Silvia de Sanjosé, Xavier Castellsagué
Journal: The Lancet Global Health (2016)

Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths.
Abstract #LB-172: Hypomethylation of a LINE-1 Promoter Activates a Truncated MET Transcript in Bladder Cancer
Authors: Erika Wolff, Hyang-Min Byun, Connie Cortez, Gerda Egger, Yvonne Tsai, Peter Nichols, Eila Skinner, Kimberly Siegmund, Allen Yang, Peter Jones, Gangning Liang
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

In addition to hypermethylation, global hypomethylation of repetitive elements such as long interspersed nuclear elements (LINE-1s or L1s) is also involved in tumorigenesis. Although there are nearly 500,000 L1s in the human genome only about 60 to 100 have potentially functional promoters, which are located within CpG islands and silenced by methylation in normal somatic cells. A full length L1 sequence has a sense promoter driving transcription of its two open reading frames and an antisense promoter driving transcription in the opposite direction that can act as an alternate promoter for surrounding genes. We show, for the first time, that the specific L1 in the MET proto-oncogene is silenced by DNA methylation, H3K9me3, and nucleosomal occupancy at the two transcriptional start sites, resulting in a tetranucleosomal structure. Upon hypomethylation the L1 antisense promoter becomes active allowing for transcription of an alternate form of MET, L1-MET. In addition to loss of DNA methylation, nucleosomes are evicted from the transcriptional start sites, resulting in a dinucleosomal structure, and those remaining contain the histone variant H2A.Z, and acetylated H3 and H3K4me3. The consequences of global hypomethylation at repetitive elements in cancer has long been the subject of speculation regarding the generation of genomic instability and potential activation of oncogenes. Ever since studies on viable yellow agouti (Avy) mice revealed that hypomethylation of a retrotransposon could induce ectopic expression of a gene and influence disease susceptibility it has been postulated that similar events may occur in humans. We show, for the first time, a direct relationship between hypomethylation of a retrotranspositional element and altered gene expression in humans and its occurance in a diseased state. Specifically, hypomethylation of a LINE-1 promoter induces an alternate transcript of the MET oncogene in bladder tumors and across the entire urothelium of tumor-bearing bladders. The robust expression of the truncated MET does not lead to the clonal expansion of cells harboring the defect, since the urothelium remains polyclonal. The widespread epigenetic alteration is more likely to be permissive for the growth of newly mutated cells rather than being directly responsible for the clonal evolution of the tumor. Finally, ROC curves based on the hypomethylation of the specific LINE-1 promoter within MET are extraordinarily specific and sensitive, providing a useful marker for the diagnosis and treatment of bladder cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-172.
The selection of a psychiatric curriculum for medical students: results of a survey
Authors: W Johnson, J Snibbe
Journal: American Journal of Psychiatry (1975)

A survey of 131 psychologists, psychiatrists, and nonpsychiatrist physicians taken to determine what doctors of medicine should know about psychiatry revealed that of the 21 topics assessed, there was a significant intergroup agreement on the 10 most important and the 5 least important topics. Interviewing, suicide evaluation, the chronically ill or dying patient, and psychiatric referral received high ratings by each group, and psychoanalytic theory, psychodynamics, and mental retardation received uniformly low ratings. The authors believe that these findings provide useful information for planning an undergraduate curriculum in psychiatry.
Thyrotropin-releasing hormone: differential antidepressant and endocrinological effects
Authors: F W Furlong, G M Brown, M F Beeching
Journal: American Journal of Psychiatry (1976)

In a double-blind study, three depressed subjects received thyrotropin-releasing hormone (TRH) on three successive days, and one subject similarly received placebo; all subjects were then given ECT. Two of the patients given TRH responded to ECT. One patient's reaction is of special significance because of her response to ECT, diminished thyroid-stimulating hormone response to TRH, increased growth hormone and prolactin response to stress, and antidepressant effect of TRH. These findings raise the possibility that previous conflicting reports about TRH's antidepressant effects stem from the combined study of endocrinologically distinct depressive subgroups and strongly suggest that there may be a specific subgroup that is responsive to TRH.
Primary cardiac angiosarcoma diagnosed by examinations for the symptom of anterior chest oppression
Authors: Yumi Yoshii, Yoshihiro Hayata, Shigeki Taniguchi, Tokiko Nakai, Chiho Obayashi, Emiko Shimoda, Masatoshi Hasegawa, Masanao Kobayashi, Kenji Nishio, Masatoshi Kanno
Journal: Annals of Oncology (2015)
Targeting β-catenin/CBP interaction in breast cancer.
Authors: A. Ring, O. Evgrafov, J. Knwoles, M. Kahn
Journal: Journal of Clinical Oncology (2011)

10516 Background: Aberrant regulation of the Wnt pathway has been shown to be associated with breast cancer. We hypothesize that (1) increased co-activator interaction of CBP with nuclear β-catenin is associated with a breast cancer stem-cell phenotype, disease progression, drug resistance, relapse and metastasis, and (2) the usage of the co-activator p300 leads to forced differentiation of cancer stem cells rendering them sensitive to existing chemotherapeutics. Methods: We have developed ICG-001, a small molecule antagonist of the CBP/β-catenin interaction. Breast cancer cells (MDA-MB-231, MDA-MB-468, MCF-7) were treated with ICG-001 and investigated for changes in proliferation, invasiveness and drug resistance. RNA sequencing and qRT-PCR were used to evaluate gene-expression. CoIP and CHiP assays demonstrated CBP/β-catenin disruption and differential coactivator usage at specific gene promoters. Protein expression was assessed by FACS and Immunoblotting. Viability assays were done to determine drug-sensitization. Stem cell assays were used to study the effect of ICG-001 on cancer stem cell populations. Preliminary in vivo studies explored the effect of ICG-001 on tumor growth. Results: ICG-001 treatment down-regulated anti-apoptotic (survivin) and mesenchymal markers (S100A4, vimentin) and up-regulated epithelial cell markers (e-cadherin, CD24) in basal-like breast cancer cells. ICG-001 disrupted the CBP/β-catenin interaction, and also re-sensitizes the hormone receptor-negative cell lines (MDA-MB-231, MDA-MB-468) to tamoxifen. ICG-001 eradicates cancer stem cell-like populations and reverses stem cell phenotype based on side population, Aldefluor and tumorsphere assays. Re-expression of CD24 is dependent on the usage of p300 in MDA-MB-231 cells (CD44+/CD24-). In vitro invasion assay demonstrated the loss of invasive potential. Preliminary in vivo studies suggested that ICG-001 alone could decrease tumor growth in a NOD/SCID mouse model. Conclusions: Antagonizing CBP/β-catenin signaling using a small molecule inhibitor is an attractive target for the treatment of resistant aggressive breast cancer and the eradication of breast cancer stem cells.
A rare cause of colonic thickening and lymphadenopathy
Authors: Emma L Culver, Lai Mun Wang, Helen Bungay, R W Chapman, J Collier
Journal: Gut (2016)

A 73-year-old retired analytic chemist presented with 4 weeks of epigastric discomfort, weight loss and loose stools. His medical history revealed pancreatic insufficiency on the background of a pancreatic mass, which had resolved 8 years previously, childhood eczema, and shellfish allergy. Laboratory investigation demonstrated an elevated C-reactive protein of 32 mm/L and IgG of 14.8 g/L with negative endomysial and auto-antibodies, normal blood count, liver function and amylase.

CT of the abdomen showed concentric thickening of the ascending colon and caecal wall with serosal abnormality and mesenteric lymphadenopathy (figure 1A, B). Ileocolonoscopy revealed an oedematous and inflamed proximal ascending colon, caecal valve and terminal ileum (figure 2A–C). The transverse colon, left colon and rectum were spared. Colonic biopsies showed an infiltrate rich in lymphocytes and plasma cells, with no granuloma or dysplasia (figure 3A⇓).



Figure 1 
(A) Coronal portal phase CT of the abdomen showing concentric thickening of the wall …
P-235 How often does the patient repeat screening colonoscopy? a study for personalized recommendation of screening colonoscopy interval
Authors: E.S. Kim, H.J. Chun, J.M. Lee, I.K. Yoo, S.H. Kim, J.M. Lee, H.S. Choi, B. Keum, Y.T. Jeen, J. Gu, S.B. Kim
Journal: Annals of Oncology (2016)
Immunotherapy With RNA Vaccination Coding For TAA In Renal Cell Carcinoma: Update On Immunological Responses and Correlation With Survival
Authors: Susanne M Rittig, Maik Häntschel, Katrin J Weimer, Annkristin Heine, Martin R Müller, Wolfram Brugger, Marius Horger, Olga Maksimovic, Arnulf Stenzl, Ingmar Hoerr, Hans-Georg Rammensee, Tobias A.W. Holderried, Lothar Kanz, Steve Pascolo, Peter Brossart
Journal: Blood (2013)
The Jak1/Jak2 Inhibitor Momelotinib Inhibits Alk2, Decreases Hepcidin Production and Ameliorates Anemia of Chronic Disease (ACD) in Rodents
Authors: Malte Asshoff, Matthew Warr, David Haschka, Piotr Tymoszuk, Verena Petzer, Egon Demetz, Pat Maciejewski, Markus Seifert, Manfred Nairz, Wilfried Posch, Peter Fowles, Guenter Weiss, Andy Whitney, Igor Theurl
Journal: Blood (2015)
Departments of Surgery and Mentorship
Authors: Gerard M. Doherty
Journal: JAMA Surgery (2016)

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High-Throughput Screening by Flow Cytometry Identifies Reduced Expression of CD48 As a Universal Characteristic of T-ALL and a Suitable Target for Minimal Residual Disease (MRD) Detection
Authors: Brent L. Wood, Greg Levin, Megan Wilson, Stuart S. Winter, Kimberly Dunsmore, Mignon L Loh, Michael J. Borowitz
Journal: Blood (2011)