tbuckley/cabot-search huggingface dataset:
Use of an Intrapericardial, Continuous-Flow, Centrifugal Pump in Patients Awaiting Heart Transplantation
Authors: Keith D. Aaronson, Mark S. Slaughter, Leslie W. Miller, Edwin C. McGee, William G. Cotts, Michael A. Acker, Mariell L. Jessup, Igor D. Gregoric, Pranav Loyalka, O.H. Frazier, Valluvan Jeevanandam, Allen S. Anderson, Robert L. Kormos, Jeffrey J. Teuteberg, Wayne C. Levy, David C. Naftel, Richard M. Bittman, Francis D. Pagani, David R. Hathaway, Steven W. Boyce
Journal: Circulation (2012)

Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes.We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly.A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.
Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells
Authors: Christopher S Bryant, Sanjeev Kumar, Sreedhar Chamala, Jay Shah, Jagannath Pal, Mahdi Haider, Shelly Seward, Aamer M Qazi, Robert Morris, Assaad Semaan, Masood A Shammas, Christopher Steffes, Ravindra B Potti, Madhu Prasad, Donald W Weaver, Ramesh B Batchu
Journal: Molecular Cancer (2010)

Abstract Background Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.
Christina Aitkenhead Herron (née Crawford)
Journal: BMJ (2006)

​FormerFormer medical officer of health Renfrew (b 1911; q Glasgow 1933; DPH), died from heart failure on 7 May 2006.



Figure 1



Christina's early posts included house jobs at Stobhill Hospital and the Royal Hospital for Sick Children, Glasgow. She developed a keen interest in public health and childhood development, gaining her DPH and writing several papers. During the second world war she worked as the assistant medical officer of health in Perth. After raising her family she returned to medicine as medical officer of health in Renfrew. She retired in 1976. Outside medicine Christina enjoyed gardening and family life. Predeceased by her husband, Henry, she leaves three children and seven grandchildren.
IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells
Authors: Marcel Batten, Nandhini Ramamoorthi, Noelyn M. Kljavin, Cindy S. Ma, Jennifer H. Cox, Hart S. Dengler, Dimitry M. Danilenko, Patrick Caplazi, Melanie Wong, David A. Fulcher, Matthew C. Cook, Cecile King, Stuart G. Tangye, Frederic J. de Sauvage, Nico Ghilardi
Journal: The Journal of Experimental Medicine (2010)

Maturation and selection of high-affinity B cell clones in the germinal center (GC) relies on support from T follicular helper (T(FH)) cells. T(FH) cells are characterized by their localization to the B cell follicle and their high expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21, which promotes immunoglobulin (Ig) class switching and production by B cells. We show that the heterodimeric cytokine IL-27 is critical for the function of T(FH) cells and for normal and pathogenic GC responses. IL-27 signaling to T cells results in the production of IL-21, a known autocrine factor for the maintenance of T(FH) cells, in a STAT3-dependent manner. IL-27 also enhances the survival of activated CD4(+) T cells and the expression of T(FH) cell phenotypic markers. In vivo, expression of the IL-27Rα chain is required to support IL-21 production and T(FH) cell survival in a T cell-intrinsic manner. The production of high-affinity antibodies is reduced, and pristane-elicited autoantibodies and glomerulonephritis are significantly diminished, in Il27ra(-/-) mice. Together, our data show a nonredundant role for IL-27 in the development of T cell-dependent antibody responses.
Antagonistic effects of gamma interferon and steroids on tissue antigenicity.
Authors: D Leszczynski, B Ferry, H Schellekens, P H van der Meide, P Häyry
Journal: The Journal of Experimental Medicine (1986)

A single injection of 10(5) U/kg of recombinant rat IFN-gamma increases the amount of tissue dendritic cells up to sixfold, and concomitantly induces the (capillary) endothelial cells to express class II MHC antigens. Both responses peak on the third day after IFN-gamma injection, and the antigen expression returns to basic levels on day 7. Simultaneous administration of 1 mg/kg/d of methylprednisolone entirely abolishes both responses. These observations demonstrate, for the first time, that IFN-gamma and steroids have antagonistic effects on class II MHC antigen presentation in tissue, and suggest that one immunosuppressive mechanism of glucocorticosteroids in organ transplantation is downregulation of graft antigenicity.
Behavior genetics and postgenomics
Authors: Evan Charney
Journal: Behavioral and Brain Sciences (2012)

The science of genetics is undergoing a paradigm shift. Recent discoveries, including the activity of retrotransposons, the extent of copy number variations, somatic and chromosomal mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challenging a series of dogmas concerning the nature of the genome and the relationship between genotype and phenotype. According to three widely held dogmas, DNA is the unchanging template of heredity, is identical in all the cells and tissues of the body, and is the sole agent of inheritance. Rather than being an unchanging template, DNA appears subject to a good deal of environmentally induced change. Instead of identical DNA in all the cells of the body, somatic mosaicism appears to be the normal human condition. And DNA can no longer be considered the sole agent of inheritance. We now know that the epigenome, which regulates gene expressivity, can be inherited via the germline. These developments are particularly significant for behavior genetics for at least three reasons: First, epigenetic regulation, DNA variability, and somatic mosaicism appear to be particularly prevalent in the human brain and probably are involved in much of human behavior; second, they have important implications for the validity of heritability and gene association studies, the methodologies that largely define the discipline of behavior genetics; and third, they appear to play a critical role in development during the perinatal period and, in particular, in enabling phenotypic plasticity in offspring. I examine one of the central claims to emerge from the use of heritability studies in the behavioral sciences, the principle of minimal shared maternal effects, in light of the growing awareness that the maternal perinatal environment is a critical venue for the exercise of adaptive phenotypic plasticity. This consideration has important implications for both developmental and evolutionary biology.
Cholesterol and risk of stroke: Cholesterol, stroke, and age
Authors: Anton J M de Craen, Gerard J Blauw, Rudi G J Westendorp
Journal: BMJ (2006)

EDITOR—Ebrahim et al studied whether blood cholesterol concentrations are predictive for haemorrhagic and ischaemic stroke in a large cohort of young and middle aged Korean civil servants.1 They found that low concentrations of cholesterol were associated with haemorrhagic stroke while high concentrations were associated with ischaemic stroke.

The …
Anticoagulants for Deep Venous Thrombosis
Authors: David K Cundiff
Journal: Journal of the Royal Society of Medicine (2001)

In their case report of superficial thrombophlebitis followed by pulmonary embolism (April 2001 JRSM, pp. 186-187) Dr Kesteven and Mr Robinson raise the question whether anticoagulants should be used to treat superficial venous thrombosis. This might be a good subject for a clinical trial; however, even the use of anticoagulants in venous thromboembolism—i.e. deep venous thrombosis (DVT) and pulmonary embolism (PE)—is open to doubt. No randomized placebo-controlled trial has ever been published supporting the efficacy or safety of anticoagulants in DVT. To justify anticoagulant treatment of DVT patients, textbooks and review articles generally lump DVT with PE and cite a placebo-controlled randomized trial of patients with PE by Barritt and Jordan1. The authors of this old and small study (n=35) used clinical signs and symptoms without lung scans or angiograms to diagnose PE. We now know that clinical suspicion of PE is confirmed by angiograms in only about 25% of cases2. Also, assignment of fatal PE as the cause of death was questionable in at least three of the five placebo group patients with severe underlying co-morbidity. In short, Barritt and Jordan's study does not qualify as scientific evidence supporting anticoagulant treatment to reduce the morbidity and/or mortality of patients with PE. Therefore, we cannot extrapolate the conclusion of Barritt and Jordan's trial to DVT patients or further extrapolate it to superficial venous thrombosis patients.

More recently in patients with DVT, Nielsen et al. compared heparin plus phenprocoumon anticoagulation with phenylbutazone in the only published randomized controlled trial3,4. It was a negative study with 1/48 anticoagulated patients and 0/42 phenylbutazone patients dying of pulmonary embolism.

For the articles and FDA correspondence detailing the case for withdrawing the indications for anticoagulants (heparins and vitamin K antagonists) in prophylaxis and treatment of venous thromboembolism, see my website: [http://hometown.aol.com/~dkcundiff/home.htm ].
Alteration at a Single Amino Acid Residue in the T Cell Receptor α Chain Complementarity Determining Region 2 Changes the Differentiation of Naive Cd4 T Cells in Response to Antigen from T Helper Cell Type 1 (Th1) to Th2
Authors: J. Magarian Blander, Derek B. Sant'Angelo, Kim Bottomly, Charles A. Janeway
Journal: The Journal of Experimental Medicine (2000)

To study whether changes in the structure of a T cell receptor (TCR) at a single peptide-contacting residue could affect T cell priming with antigenic peptide, we made transgenic mice with a point mutation in the TCR α chain of the D10.G4.1 (D10) TCR and bred them to D10 β chain transgenic mice. The mutation consisted of a leucine to serine substitution at position 51 (L51S), which we had already established contacted the second amino acid of the peptide such that the response to the reference peptide was reduced by ∼100-fold. A mutation in the reference peptide CA134–146 (CA-WT) from the arginine at peptide position 2 to glycine (R2G) restored full response to this altered TCR. When we examined in vitro priming of naive CD4 T cells, we observed that the response to doses of CA-WT that induced T helper cell type 1 (Th1) responses in naive CD4 T cells from mice transgenic for the D10 TCR gave only Th2 responses in naive CD4 T cells derived from the L51S. However, when we primed the same T cells with the R2G peptide, we observed Th1 priming in both D10 and L51S naive CD4 T cells. We conclude from these data that a mutation in the TCR at a key position that contacts major histocompatibility complex–bound peptide is associated with a shift in T cell differentiation from Th1 to Th2.
Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non-small-cell lung cancer (NCIC CTG BR.26): a double-blind, randomised, phase 3 trial
Authors: Peter M Ellis, Frances A Shepherd, Michael Millward, Francesco Perrone, Lesley Seymour, Geoffrey Liu, Sophie Sun, Byoung Chul Cho, Alessandro Morabito, Natasha B Leighl, Martin R Stockler, Christopher W Lee, Rafal Wierzbicki, Victor Cohen, Normand Blais, Randeep S Sangha, Adolfo G Favaretto, Jin Hyoung Kang, Ming-Sound Tsao, Carolyn F Wilson, Zelanna Goldberg, Keyue Ding, Glenwood D Goss, Penelope Ann Bradbury
Journal: The Lancet Oncology (2014)
Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer
Authors: Seung-Hyun Jung, Sun Shin, Min Sung Kim, In-Pyo Baek, Ji Youl Lee, Sung Hak Lee, Tae-Min Kim, Sug Hyung Lee, Yeun-Jun Chung
Journal: European Urology (2015)

Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown.Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA.We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization.Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared.The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied.HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression.In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA.
Using Tobacco-Industry Marketing Research to Design More Effective Tobacco-Control Campaigns
Authors: Pamela M. Ling
Journal: JAMA (2002)

To improve tobacco-control efforts by applying tobacco-industry marketing research and strategies to clinical and public health smoking interventions, we analyzed previously secret tobacco-industry marketing documents. In contrast to public health, the tobacco industry divides markets and defines targets according to consumer attitudes, aspirations, activities, and lifestyles. Tobacco marketing targets smokers of all ages; young adults are particularly important. During the 1980s, cost affected increasing numbers of young and older smokers. During the 1990s, eroding social acceptability of smoking emerged as a major threat, largely from increasing awareness of the dangers of secondhand smoke among nonsmokers and smokers. Physicians and public health professionals should use tobacco-industry psychographic approaches to design more relevant tobacco-control interventions. Efforts to counter tobacco marketing campaigns should include people of all ages, particularly young adults, rather than concentrating on teens and young children. Many young smokers are cost sensitive. Tobacco-control messages emphasizing the dangers of secondhand smoke to smokers and nonsmokers undermine the social acceptability of smoking.
Closed-Loop Insulin Delivery During Pregnancy Complicated by Type 1 Diabetes
Authors: Helen R. Murphy, Daniela Elleri, Janet M. Allen, Julie Harris, David Simmons, Gerry Rayman, Rosemary Temple, David B. Dunger, Ahmad Haidar, Marianna Nodale, Malgorzata E. Wilinska, Roman Hovorka
Journal: Diabetes Care (2011)

This study evaluated closed-loop insulin delivery with a model predictive control (MPC) algorithm during early (12-16 weeks) and late gestation (28-32 weeks) in pregnant women with type 1 diabetes.
Intramyocardial injection of naked DNA encoding HIF-1 /VP16 hybrid to enhance angiogenesis in an acute myocardial infarction model in the rat
Authors: K.-G. Shyu, M.-T. Wang, B.-W. Wang, C.-C. Chang, J.-G. Leu, P. Kuan, H. Chang
Journal: Cardiovascular Research (2002)

The therapeutic utility of hypoxia-inducible factor-1 (HIF-1) transcriptional regulatory system for ischemic hindlimb has been demonstrated. It is not yet known whether this transcriptional regulatory system can be used as a therapeutic strategy to enhance collateral vessel formation in myocardial tissues, where acute hypoxia occurs due to inadequate perfusion. We aimed to test the hypothesis that exogenous administration of HIF-1alpha/VP16 could enhance collateral vessel formation in a rat acute myocardial infarction model. Sprague-Dawley rats received ligation of the proximal left anterior descending coronary artery to induce acute myocardial infarction. Immediately after the ligation, 50 microg total plasmid DNA (control, plasmid encoding human vascular endothelial growth factor (pVEGF(165)), or pHIF-1alpha/VP16) was injected into the infarct area at three locations. Reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of HIF-1alpha and VEGF mRNA in the myocardium, but not in other organs at days 3 and 7. The infarct size significantly decreased from 37+/-4% (control) to 24+/-2% in the VEGF-treated group and 23+/-2% in the HIF-1alpha/VP16 treated group (P<0.05). Capillary density also significantly increased from 550+/-75/mm(2) (control) to 850+/-75/mm(2) in the VEGF group and 850+/-50/mm(2) in the HIF-1alpha/VP16-treated group (P<0.01). Combined therapy with HIF-1alpha/VP16 and VEGF resulted in higher capillary density (1230+/-50/mm(2)) than treatment with either therapy alone. Regional myocardial blood flow was also higher in the treated groups than in the control. Plasma levels of VEGF were also significantly higher in the HIF-1alpha/VP16 and VEGF-treated group than in the control group. The HIF-1alpha/VP16 hybrid transcription factor is able to reduce infarct size and enhance neovascularization in an acute ischemic myocardium. The potency of VEGF and HIF-1alpha/VP16 hybrid as therapeutic angiogenic factors in acute hypoxic myocardium is similar.
Expression of p53, p21 (Waf1/Cip1/Sdi1) and Fas antigen in collagen vascular and granulomatous lung diseases
Authors: R Kunitake, K Kuwano, H Miyazaki, M Kawasaki, N Hagimoto, M Fujita, Y Kaneko, N Hara
Journal: European Respiratory Journal (1998)

Fas is expressed in various cells and transduces the cell death signal. p21 is a mediator of p53-dependent G1 arrest associated with deoxyribonucleic acid (DNA) damage. The upregulation of p53 and p21 associated with DNA damage in idiopathic pulmonary fibrosis has been described previously. In this study, p53, p21, and Fas expression and DNA damage were examined in interstitial pneumonia associated with collagen vascular diseases (CVD-IP). DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labelling (TUNEL) and p53, p21 and Fas proteins were detected by immunohistochemistry in 13 cases of CVD-IP, 13 of sarcoidosis, seven of hypersensitivity pneumonitis (HP) and eight control patients with normal lung parenchyma. TUNEL-positive signals were found in bronchiolar or alveolar epithelial cells in 11 of 13 (85%) specimens of CVD-IP, but not in sarcoidosis, HP or controls, except for a case of chronic HP with pulmonary fibrosis. p53, p21 and Fas were detected in bronchiolar or alveolar epithelial cells in nine (69%), 10 (77%) and 12 (92%) of 13 specimens of CVD-IP, respectively, but not in sarcoidosis, HP or controls, except for a case of chronic HP. These results suggest that the upregulation of p53, p21 and Fas in bronchiolar and alveolar epithelial cells associated with deoxyribonucleic acid damage may participate in the process of pulmonary fibrosis in interstitial pneumonia associated with collagen vascular diseases and chronic hypersensitivity pneumonitis.
Big Heart, Tongue, and Kidneys—Stiff Intestines
Authors: Bert Lincoln Pear
Journal: JAMA (1979)

AMYLOIDOSIS can no longer be considered a rare disease. Localized deposits have been found within the heart, lung, kidney, liver, pancreas, and brain in as high as 16% of postmortem studies when appropriate stains were used.<sup>1</sup>Amyloid occurs within the heart in a substantial number of patients older than 60 years. This incidence increases with aging and can either contribute to heart failure or be its only cause.<sup>2,3</sup> Generalized amyloidosis may arise primarily or may be associated with plasmacytosis or multiple myeloma, but may also be a secondary accompaniment of a large variety of seemingly unrelated disorders (Table).<sup>4</sup>It is also a manifestation of aging. Amyloidosis is characterized by the extracellular deposition of an abnormal fibrillar protein between parenchymal cells and within connective tissues and blood vessels. Not all amyloid protein is alike chemically, although its fibrillar ultrastructure is similar. The underlying pathogenesis relates to a proteolytic