tbuckley/cabot-search huggingface dataset:
eIF4E Activation Is Commonly Elevated in Advanced Human Prostate Cancers and Significantly Related to Reduced Patient Survival
Authors: Jeremy R. Graff, Bruce W. Konicek, Rebecca L. Lynch, Chad A. Dumstorf, Michele S. Dowless, Ann M. McNulty, Stephen H. Parsons, Leslie H. Brail, Bruce M. Colligan, Jonathan W. Koop, Bernadette M. Hurst, James A. Deddens, Blake L. Neubauer, Louis F. Stancato, Harry W. Carter, Larry E. Douglass, Julia H. Carter
Journal: Cancer Research (2009)

Elevated eukaryotic translation initiation factor 4E (eIF4E) function induces malignancy in experimental models by selectively enhancing translation of key malignancy-related mRNAs (c-myc and BCL-2). eIF4E activation may reflect increased eIF4E expression or phosphorylation of its inhibitory binding proteins (4E-BP). By immunohistochemical analyses of 148 tissues from 89 prostate cancer patients, we now show that both eIF4E expression and 4E-BP1 phosphorylation (p4E-BP1) are increased significantly, particularly in advanced prostate cancer versus benign prostatic hyperplasia tissues. Further, increased eIF4E and p4E-BP1 levels are significantly related to reduced patient survival, whereas uniform 4E-BP1 expression is significantly related to better patient survival. Both immunohistochemistry and Western blotting reveal that elevated eIF4E and p4E-BP1 are evident in the same prostate cancer tissues. In two distinct prostate cancer cell models, the progression to androgen independence also involves increased eIF4E activation. In these prostate cancer cells, reducing eIF4E expression with an eIF4E-specific antisense oligonucleotide currently in phase I clinical trials robustly induces apoptosis, regardless of cell cycle phase, and reduces expression of the eIF4E-regulated proteins BCL-2 and c-myc. Collectively, these data implicate eIF4E activation in prostate cancer and suggest that targeting eIF4E may be attractive for prostate cancer therapy.
Cardiac Stem Cell Biology
Authors: Elena Matsa, Karim Sallam, Joseph C. Wu
Journal: Circulation Research (2014)

Cardiac regeneration strategies and de novo generation of cardiomyocytes have long been significant areas of research interest in cardiovascular medicine. In this review, we outline a variety of common cell sources and methods used to regenerate cardiomyocytes and highlight the important role that key Circulation Research articles have played in this flourishing field.
Deception by Design: Pharmaceutical Promotion in the Third World
Authors: T. I. Bhutta
Journal: BMJ (1996)

Joel Lexchin Consumers International Regional Office for Asia and the Pacific, $15 + postage, pp 91 ISBN 967 9973 68 9

Developing countries are being flooded with drugs, most of which are useless, expensive, or dangerous. All too often the pharmaceutical industry's promotion of drugs leads to irrational prescribing by doctors. Companies spend about 20-30% of their sales budget on promotion, providing free samples to doctors to create demand for their products. In recent years in many developing countries with developing market economies, prices of medicines have sometimes risen by 400-500%.

The main sources of information on new and existing products are the drug companies, either through mailings or visits by …
Kids, Cholesterol, Carotids, and Coronaries
Authors: Michael I. Weintraub
Journal: JAMA (1991)

<h3>To the Editor.</h3> —The commentary by Resnicow et al<sup>1</sup>is confusing and misdirected. Scientific knowledge is currently inadequate in predicting that children with elevated cholesterol levels will become symptomatic adults. To focus only on cholesterol metabolism as the sole biologic marker for adult atherosclerosis appears unjustified. Atherosclerosis begins in childhood, yet the events that promote it are not completely understood. Previous knowledge relied upon autopsy data demonstrating fatty streaks and fibrous plaques in the aorta and coronary vessels.<sup>2</sup>It would be misleading to conclude that the actual presence of plaque would correlate with future cardiovascular and cerebrovascular disease since the ischemic manifestations of elevated cholesterol and the presence of plaque are unpredictable and are not linearly related to stroke or heart disease. Thus, the search for alternative biological markers is reasonable and necessary. Current technology can now accurately measure coronary and carotid diameters, plaque, and blood flow. In
Determinants of cardiac noradrenaline depletion in human congestive failure
Authors: V. DEQUATTRO, T. NAGATSU, A. MENDEZ, J. VERSKA
Journal: Cardiovascular Research (1973)

Biopsies of myocardium were obtained from patients with acquired and congenital heart disease at the time of cardiopulmonary bypass and assayed for content of noradrenaline and the activities of the rate limiting biosynthetic enzyme — tyrosine hydroxylase, and the degradative enzymes — monoamine oxidase and catechol-0-methyl transferase (COMT). The 64% reduction in myocardial noradrenaline in patients with congestive failure was related directly to a 54% reduction in tyrosine hydroxylase activity and inversely to an 88% increase in mean wedge pulmonary artery pressure. The activity of the extraneuronal enzyme, COMT, was increased 115% in hearts of those with congestive failure, due in part to fibrotic replacement of innervated contractile muscle.
A Link between Benzyl Isothiocyanate-Induced Cell Cycle Arrest and Apoptosis: Involvement of Mitogen-Activated Protein Kinases in the Bcl-2 Phosphorylation
Authors: Noriyuki Miyoshi, Koji Uchida, Toshihiko Osawa, Yoshimasa Nakamura
Journal: Cancer Research (2004)

Abstract In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis and the involvement of mitogen-activated protein kinases (MAPKs). The exposure of Jurkat human T-cell leukemia cells to BITC resulted in the inhibition of the G2-M progression that coincided with the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G2-M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We also confirmed that BITC activated c-Jun N-terminal kinase (JNK) and p38 MAPK, but not extracellular signal-regulated kinase, at the concentration required for apoptosis induction. An experiment using a JNK-specific inhibitor SP600125 or a p38 MAPK inhibitor SB202190 indicated that BITC-induced apoptosis might be regulated by the activation of these two kinases. Conversely, BITC is likely to confine the Jurkat cells in the G2-M phase mainly through the p38 MAPK pathway because only the p38 MAPK inhibitor significantly attenuated the accumulation of inactive phosphorylated Cdc2 protein and the G2-M-arrested cell numbers. We reported here for the first time that the antiapoptotic Bcl-2 protein was phosphorylated by the BITC treatment without significant alteration of the Bcl-2 total protein amount. This was abrogated by a JNK specific inhibitor SP600125 at the concentration required for specific inhibition of the c-Jun phosphorylation. Moreover, the spontaneous phosphorylation of antiapoptotic Bcl-2 in the G2-M synchronized cells was enhanced synergistically by the BITC treatment. Involvement of the MAPK activation in the Bcl-2 phosphorylation and apoptosis induction also was observed in HL-60 and HeLa cells. Thus, we identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC.
Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia
Authors: Yuzo Suzuki, Takafumi Suda, Koushi Yokomura, Masako Suzuki, Michio Fujie, Kazuki Furuhashi, Dai Hahimoto, Noriyuki Enomto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Yutaka Nakano, Hirotoshi Nakamura, Kingo Chida
Journal: Journal of Infection (2011)
Principles of Molecular Medicine
Authors: Matthew Rusk
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes6 April 1999Principles of Molecular MedicineMatthew Rusk, MDMatthew Rusk, MDUniversity of Pennsylvania, Philadelphia, Pennsylvania.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-7-199904060-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Jameson JL; ed. 1123 pages. Totowa, NJ: Humana; 1998. $175.00. ISBN 0896035298. Order phone 201-256-1699.Field of medicine: Genetics and molecular biology.Format: Hardcover book.Audience: Geneticists and interested specialists and subspecialists in all fields of medicine.Purpose: To introduce the reader to advances in molecular biology and genetics in medicine.Content: This comprehensive textbook is arranged by subspecialty. The introduction reviews basic cellular genetics and recombinant genetic techniques and includes a discussion of the history and development of genetic testing. Each chapter is edited by an expert in a particular subspecialty and concentrates on areas in which recent advances ... Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 April 1999Volume 130, Issue 7Page: 624KeywordsClinical epidemiologyForecastingGenetic diseasesGenetic testingHematology and oncologyMedical geneticsMetabolic disordersMolecular biologyNeurologySub-specialty care Issue Published: 6 April 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Transfer of human myocarditis into severe combined immunodeficiency mice.
Authors: P L Schwimmbeck, C Badorff, H P Schultheiss, B E Strauer
Journal: Circulation Research (1994)

Severe combined immunodeficiency (SCID) mice possess neither T nor B lymphocytes and are thus suitable recipients for lymphocytes of different species. Because autoimmune mechanisms are suspected in the pathogenesis of myocarditis (MC), we attempted to determine whether peripheral blood lymphocytes (PBLs) from patients with MC could be transferred into SCID mice and whether they had an autoimmunologic effect. Groups of three mice each were injected intraperitoneally with up to 50 million PBLs from five MC patients with autoantibodies against the adenine nucleotide translocator (ANT), a myocardial autoantigen. The PBLs from three healthy blood donors were used as controls. After 60 days, human PBLs could be demonstrated in the peripheral blood of the SCID mice transfused with the PBLs of MC patients, representing up to 9.9% of the peripheral blood mononuclear cells. The transfused SCID mice sera showed human immunoglobulin levels of up to 3 mg/mL, both IgG and IgM. Autoantibodies against ANT were present in the mice receiving PBLs from MC patients but not from the control subjects. In addition, infiltrating human lymphocytes were present in the hearts of the SCID mice transfused with PBLs from MC patients. The presence of an ongoing autoimmune process in the SCID mice transfused with PBLs from MC patients is suggested by increased levels of soluble interleukin-2 receptor in the serum in contrast to SCID mice transfused with PBLs from healthy blood donors. We conclude that the autoimmune reactions seen in human MC can be transferred to SCID mice by the transfer of PBLs from MC patients. These findings stress the significance of autoimmune mechanisms in the pathogenesis of human MC.
Deletion of alanine 2201 in the FVIII C2 domain results in mild hemophilia A by impairing FVIII binding to VWF and phospholipids and destroys a major FVIII antigenic determinant involved in inhibitor development
Authors: Roseline d'Oiron, Jean-Maurice Lavergne, Renaud Lavend'homme, Abdellah Benhida, Jean-Claude Bordet, Claude Negrier, Kathelijne Peerlinck, Jos Vermylen, Jean-Marie Saint-Remy, Marc Jacquemin
Journal: Blood (2003)
A Symptom of Discontent
Authors: Edward W. Campion
Journal: New England Journal of Medicine (2001)

Many physicians today believe that they are not able to spend as much time with patients as they did in the past. They blame our confused health care system and are concerned about not having enough time to address the many needs of their patients. In this issue of the Journal, Mechanic et al. show that between 1989 and 1998 the length of office visits did not decline, as was widely assumed.1 In fact, it increased. The trend toward longer office visits was observed for both visits covered by a managed-care or other prepaid health plan (prepaid visits) and non-prepaid . . .
Biologic and clinical significance of CD7 expression in acute myeloid leukemia
Authors: Anurag Saxena, David P. Sheridan, Robert T. Card, A.M. McPeek, C.C. Mewdell, Leonard F. Skinnider
Journal: American Journal of Hematology (1998)

CD7 antigen, a T-cell lineage associated antigen, is expressed in a minority of patients with acute myeloid leukemia (AML). The biologic and clinical significance of this finding is not clearly established. In this retrospective study of patients with de novo acute myeloid leukemia, we have identified CD7 expression and analyzed its association with markers expressed early in hemopoietic ontogeny and clinical parameters. Among 60 consecutive AML patients, we found six (10%) expressing CD7 on leukemic cells. There were five males and one female and the mean age was 59.6 years (age range: 32-76 years) with no demographic peculiarities. The FAB subtypes were: M0 (2), M1 (1), M2 (1), and M4 (2). CD7 expression was associated with immature antigens CD34, HLA-DR, and terminal deoxynucleotidyl transferase (TdT) and antigen receptor gene rearrangements (rearrangements of T-cell receptor gamma chain in 6/6 and immunoglobulin heavy chain in 2/6). Hepatomegaly was present in three and this was associated with splenomegaly with lymphadenopathy in one patient. Mediastinal or central nervous system involvement was absent. Complete remission was achieved in two patients with standard chemotherapy; one of these is in remission and alive (5 years later), while one died following relapse 9 months later. Three patients had significantly lower response to standard therapeutic regimen (two died during induction and one died 7 months later without ever achieving complete remission). One patient has been excluded in determining the prognostic significance of CD7 due to early death. Our results suggest origin of CD7+ AML from early hemopoietic precursors and indicate biologic aggressiveness in a significant proportion of patients. We suggest evaluation of CD7 in all patients with AML at the time of diagnosis in view of poor clinical outcome.
"Been to Africa".
Authors: A. Fiander, D. Hughes
Journal: BMJ (1989)

The main drawback for young doctors from developed countries working in Africa or other developing area is the lack of supervision.  Medical and nursing care standards are low with poor facilities and infrastructure and the problems encountered are enormous.  Attitudes and expectations will have to change and mistakes will inevitably occur.  Additional frustrations are poor motivation of the local staff lack of essential supplies and the doctor coming down with tropical diseases.  However much can be gained by this type of experience:  basic skills will be improved and self-confidence gained in ones own judgement; technical abilities will grow because of limited resources and equipment and the need to justify their use only when absolutely necessary.  Management and administrative skills will also improve and opportunities found for teaching and making little changes.  The personal thanks and appreciation of the patients despite their great poverty and their quiet suffering also adds to the experience.  Valuable lessons can be learned from the nurses both medically and culturally and they have been accepting and friendly.  Planning for such an experience takes 1-2 years.  It is hard to find suitable jobs and one should seek the advice of consultants or other experts with experience abroad.  Organizations concerned with health in developing countries such as the Institute of Child Health International Centre for Eye Health Christian Medical Fellowship are resources for obtaining positions.  Placement may be with a missionary organization nongovernmental organization college program or a hospital exchange.  The best time is when the doctor has completed the specialist exams and has something specific to offer.  A 2-year contract is a reasonable time period to plan for.  Keeping up with the literature and some standard teaching tools are important and publishing the experiences gained will be valuable for others.  Prepare for this by keeping records of work including a log of operations.
Needle Biopsy of the Liver
Authors: R. S. Murley
Journal: BMJ (1959)

<b>Objective: </b> To investigate the relationship between the apolipoprotein (ApoE) ε4 allele and memory performance (verbal and nonverbal) in patients with medically intractable temporal lobe epilepsy (TLE) who underwent temporal lobectomy. <b>Methods: </b> Presurgical and postsurgical memory performance was examined in 87 adult patients with TLE (ε4 = 22; non-ε4 = 65) to determine whether the expression of ApoE-ε4 may be associated with memory performance in this population and to examine how this relationship may be affected by duration of epilepsy. <b>Results: </b> There was a significant interaction between ApoE-ε4 status and duration of epilepsy such that ε4 carriers with a long duration of epilepsy demonstrated the poorest memory performance on both verbal and nonverbal measures. This relationship was observed both before and after temporal lobectomy, with little change in test performance over time. <b>Conclusions: </b> The ApoE-ε4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy.
Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium
Authors: Wangde Dai, Sharon L. Hale, Bradley J. Martin, Jin-Qiang Kuang, Joan S. Dow, Loren E. Wold, Robert A. Kloner
Journal: Circulation (2005)

Mesenchymal stem cells (MSCs) have the potential to replace infarct scar, but the long-term effects are unknown. We studied short- and long-term effects of MSC transplantation on left ventricular (LV) function in a rat myocardial infarction model.Saline (n=46) or MSCs labeled with 1,1'-dioctadecyl-3,3,3'3'-testramethylindocarbocyanine perchlorate (DiI; n=49, 2x10(6) cells each) were injected into the scar of a 1-week-old myocardial infarction in Fischer rats. The presence and differentiation of engrafted cells and their effect on LV ejection fraction was assessed. At 4 weeks, LV stroke volume was significantly greater in the MSC-treated group (145+/-9 microL) than in the saline group (122+/-3 microL, P=0.032), and LV ejection fraction was significantly greater in MSC-treated animals (43.8+/-1.0%) than in the saline group (38.8+/-1.1%, P=0.0027). However, at 6 months, these benefits of MSC treatment were lost. DiI-positive cells were observed in the MSC group at 2 weeks and at 3 and 6 months. Expression of the muscle-specific markers alpha-actinin, myosin heavy chain, phospholamban, and tropomyosin was not observed at 2 weeks in DiI-positive cells. At 3 and 6 months, the DiI-positive cells were observed to express the above muscle-specific markers, but they did not fully evolve into an adult cardiac phenotype. Some of the DiI-positive cells expressed von Willebrand factor.Allogeneic MSCs survive in infarcted myocardium as long as 6 months and express markers that suggest muscle and endothelium phenotypes. MSCs improved global LV function at 4 weeks; however, this benefit was transient, which suggests a possible early paracrine effect.
323. Transcriptional Targeting of Viral Gene Transfer by Human Hexokinase II Promoter
Authors: Ann-Marie Maatta, Sanna Korja, Tanja Hakkarainen, Jarmo Wahlfors, Kimmo Mäkinen, Esko Alhava, Riikka Pellinen
Journal: Molecular Therapy (2005)

Targeting is one of the major challenges in cancer gene therapy. One approach is to use specific promoters to limit the expression of the transgene to specific cells. It has been demonstrated that rat hexokinase II (HKII) promoter is activated in human tumour cells but not in normal cells. Also human HKII-promoter is known to be active in tumour cells and transcriptionally activated in cells that have mutated p53 gene.
Extraosseous Localization of Technetium-99m MDP in Benign Cystic Teratoma
Authors: CLAYTON FULLER, JOE C. LEONARD
Journal: Clinical Nuclear Medicine (1986)

Two cases of primary retroperitoneal benign teratoma, in which Tc-99m MDP localized in the primary tumor are presented. Localization of bone-imaging agents in neuroblastoma has been reported but, extraosseous localization of bone-imaging agents in teratomas has not been confirmed.
Clues for a possible role of senescent T cells in giant cell arteritis pathogenesis
Authors: K. S. M. van der Geest, W. H. Abdulahad, M. G. Huitema, B. J. Kroesen, E. Brouwer, A. M. H. Boots
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> T cells are considered major players in the development of giant cell arteritis (GCA). To date most attention has been focused on Th1 and Th17 cells. However, the contribution of senescent T cells to this strictly ageing-associated vasculitis remains obscure. The purpose of this study was to provide clues whether senescent T cells play a role in GCA pathogenesis. Therefore we assessed frequencies of senescent T cells and their expression of the natural killer marker CD161 in patients with GCA and healthy controls. CD161 has been reported to identify cells with a pro-inflammatory cytokine repertoire (eg, interferon γ and interleukin 17). <h3>Methods</h3> Peripheral blood of seven untreated GCA-patients and eight age/sex matched healthy controls was obtained. Using flow cytometry, senescent (or terminally differentiated) T cells were defined as CD45RO-CCR7- cells within the CD4 and CD8 T cell gates. In addition, the naïve (CD45RO-CCR7+), central memory (CD45RO+CCR7+) and effector memory (CD45RO+CCR7-) T cell subsets were identified. Expression of CD161 was assessed in each of these subsets. <h3>Results</h3> Frequencies of senescent, naïve and central memory CD4 T cells were similar in GCA-patients and controls, whereas a trend towards decreased CD4 effector memory cells was observed in patients (23% vs 34%). The CD4 senescent T cell subset of GCA patients contained more CD161 cells compared to healthy controls (4,4% vs 1,6%). Also in the CD4 effector memory subset of patients we observed a trend towards more CD161 cells (33% vs 21%). Frequencies of CD8 naïve, central memory, effector memory and terminally differentiated subsets were similar in patients and controls. In addition no differences were found for CD161 expression in CD8 T cells. <h3>Conclusion</h3> We found one clue suggesting a role for senescent T cells in GCA: namely, an increased expression of CD161 by CD4 senescent T cells in GCA patients. This could reflect a natural killer-like phenotype in these cells, associated with high production of IFNγ and cytotoxic effector molecules. The same might be true for the CD4 effector memory subset of GCA patients, since we observed a trend towards more CD161 expression in these cells. In addition we found a trend towards decreased frequencies of circulating CD4 effector memory cells in GCA-patients. This may suggest that these cells preferentially migrate to the site of inflammation, as previously observed in Wegener9s granulomatosis.1