tbuckley/cabot-search huggingface dataset:
High-Throughput Screening Identifies Two Classes of Antibiotics as Radioprotectors: Tetracyclines and Fluoroquinolones
Authors: Kwanghee Kim, Julianne M. Pollard, Andrew J. Norris, J. Tyson McDonald, Yingli Sun, Ewa Micewicz, Kelly Pettijohn, Robert Damoiseaux, Keisuke S. Iwamoto, James W. Sayre, Brendan D. Price, Richard A. Gatti, William H. McBride
Journal: Clinical Cancer Research (2009)

Discovery of agents that protect or mitigate normal tissue from radiation injury during radiotherapy, accidents, or terrorist attacks is of importance. Specifically, bone marrow insufficiency, with possible infection due to immunosuppression, can occur after total body irradiation (TBI) or regional irradiation and is a major component of the acute radiation syndrome. The purpose of this study was to identify novel radioprotectors and mitigators of the hematopoietic system.High-throughput screening of small-molecule libraries was done using viability of a murine lymphocyte line as a readout with further validation in human lymphoblastoid cells. The selected compounds were then tested for their ability to counter TBI lethality in mice.All of two major classes of antibiotics, tetracyclines and fluoroquinolones, which share a common planar ring moiety, were radioprotective. Furthermore, tetracycline protected murine hematopoietic stem/progenitor cell populations from radiation damage and allowed 87.5% of mice to survive when given before and 35% when given 24 h after lethal TBI. Interestingly, tetracycline did not alter the radiosensitivity of Lewis lung cancer cells. Tetracycline and ciprofloxacine also protected human lymphoblastoid cells, reducing radiation-induced DNA double-strand breaks by 33% and 21%, respectively. The effects of these agents on radiation lethality are not due to the classic mechanism of free radical scavenging but potentially through activation of the Tip60 histone acetyltransferase and altered chromatin structure.Tetracyclines and fluoroquinolones can be robust radioprotectors and mitigators of the hematopoietic system with potential utility in anticancer radiotherapy and radiation emergencies.
Direct Photoaffinity Labeling of Tubulin With Taxol
Authors: S. Rao, S. B. Horwitz, I. Ringel
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Direct Photoaffinity Labeling of Tubulin With Taxol Get access Srinivasa Rao, Srinivasa Rao Department of Molecular Pharmacology and cell Biology, Albert Einstein College of MedicineBronx, N.Y Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Band Horwitz, Susan Band Horwitz * Department of Molecular Pharmacology and cell Biology, Albert Einstein College of MedicineBronx, N.Y * Correspondence to: Susan B. Horwitz, Ph.D., Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Search for other works by this author on: Oxford Academic PubMed Google Scholar Israel Ringel Israel Ringel Department of Pharmacology, The Hebrew University-Hadassah Medical SchoolJerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 10, 20 May 1992, Pages 785–788, https://doi.org/10.1093/jnci/84.10.785 Published: 20 May 1992 Article history Received: 27 December 1991 Revision received: 29 January 1992 Accepted: 07 February 1992 Published: 20 May 1992
Hair follicle–derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma
Authors: Takeya Adachi, Tetsuro Kobayashi, Eiji Sugihara, Taketo Yamada, Koichi Ikuta, Stefania Pittaluga, Hideyuki Saya, Masayuki Amagai, Keisuke Nagao
Journal: Nature Medicine (2015)
Functional Effector Memory T Cells Enrich the Peritoneal Cavity of Patients Treated with Peritoneal Dialysis
Authors: Gareth W. Roberts, Duncan Baird, Kathleen Gallagher, Rhiannon E. Jones, Christopher J. Pepper, John D Williams, Nicholas Topley
Journal: Journal of the American Society of Nephrology (2009)

The frequency and severity of episodes of peritonitis adversely affect the structure and function of the peritoneal membrane in patients treated with peritoneal dialysis (PD), but the underlying mechanisms are not well understood. Alterations in the phenotype and function of resident peritoneal cells may contribute. Because effector memory T cells play a pivotal role in maintaining peripheral tissue immunity, we hypothesized that these cells may initiate or perpetuate the peritoneal inflammatory response. Here, we characterized the phenotype and effector function of peritoneal memory T cells. We found that functional effector memory T cells capable of mounting long-term recall responses enrich the peritoneal cavity of PD patients. Peritoneal T cells were able to mount a Th1-polarized response to recall antigens, and these responses were greater in peritoneal T cells compared with T cells in the peripheral blood. We also observed that the peritoneal T cells had altered telomeres; some cells had ultrashort telomeres, suggesting a highly differentiated local population. In summary, we describe a resident population of memory T cells in the peritoneum of PD patients and speculate that these cells form part of the first line of defense against invading pathogens.
Addressing the Soy and Breast Cancer Relationship: Review, Commentary, and Workshop Proceedings
Authors: Mark Messina, Worta McCaskill-Stevens, Johanna W. Lampe
Journal: JNCI Journal of the National Cancer Institute (2006)

The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.
Altered Neural Substrates of Cognitive Control in Childhood ADHD: Evidence From Functional Magnetic Resonance Imaging
Authors: Chandan J. Vaidya, Silvia A. Bunge, Nicole M. Dudukovic, Christine A. Zalecki, Glen R. Elliott, John D.E. Gabrieli
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The study compared the neural bases of two cognitive control operations, interference suppression and response inhibition, between children with and children without attention deficit hyperactivity disorder (ADHD). METHOD: Ten children (7–11 years of age) with combined-type ADHD and 10 comparison subjects matched for age and gender underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Functional maps were generated through group averaging and performance-based correlational analyses. RESULTS: Interference suppression in ADHD subjects was characterized by reduced engagement of a frontal-striatal-temporal-parietal network that subserved healthy performance. In contrast, response inhibition performance relied upon different regions in the two groups, frontal-striatal in comparison subjects but right superior temporal in ADHD children. CONCLUSIONS: Alteration in the neural basis of two cognitive control operations in childhood ADHD was characterized by distinct, rather than unitary, patterns of functional abnormality. Greater between-group overlap in the neural network activated for interference suppression than in response inhibition suggests that components of cognitive control are differentially sensitive to ADHD. The ADHD children's inability to activate the caudate nucleus constitutes a core abnormality in ADHD. Observed functional abnormalities did not result from prolonged stimulant exposure, since most children were medication naive.
Expression of IFN-β Enhances Both Efficacy and Safety of Oncolytic Vesicular Stomatitis Virus for Therapy of Mesothelioma
Authors: Candice L. Willmon, Vassiliki Saloura, Zvi G. Fridlender, Phonphimon Wongthida, Rosa Maria Diaz, Jill Thompson, Timothy Kottke, Mark Federspiel, Glen Barber, Steven M. Albelda, Richard G. Vile
Journal: Cancer Research (2009)

Abstract Our preclinical and clinical trials using a replication-defective adenoviral vector expressing IFN-β have shown promising results for the treatment of malignant mesothelioma. Based on the hypotheses that a replication-competent vesicular stomatitis virus (VSV) oncolytic vector would transduce more tumor cells in vivo, that coexpression of the immunostimulatory IFN-β gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with VSV-mediated virotherapy, and that virus-derived IFN-β would add further safety to the VSV platform, we tested the use of IFN-β as a therapeutic transgene expressed from VSV as a novel treatment for mesothelioma. VSV-IFN-β showed significant therapy against AB12 murine mesotheliomas in the context of both local and locoregional viral delivery. Biologically active IFN-β expressed from VSV added significantly to therapy compared with VSV alone, dependent in part on host CD8+ T-cell responses. Immune monitoring suggested that these antitumor T-cell responses may be due to a generalized T-cell activation rather than the priming of tumor antigen–specific T-cell responses. Finally, IFN-β also added considerable extra safety to the virus by providing protection from off-target viral replication in nontumor tissues and protected severe combined immunodeficient mice from developing lethal neurotoxicity. The enhanced therapeutic index provided by the addition of IFN-β to VSV therefore provides a powerful justification for the development of this virus for future clinical trials. [Cancer Res 2009;69(19):7713–20]
Elucidating Nature's Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders
Authors: Hannah V. Carey, Sandra L. Martin, Barbara A. Horwitz, Lin Yan, Shannon M. Bailey, Jason Podrabsky, Jay F. Storz, Rudy M. Ortiz, Renee P. Wong, David A. Lathrop
Journal: Circulation Research (2012)

Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature's solutions to heart, lung, blood, and sleep disorders through future research in this area.
Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study
Authors: Deepali Kumar, Marian G Michaels, Michele I Morris, Michael Green, Robin K Avery, Catherine Liu, Lara Danziger-Isakov, Valentina Stosor, Michele Estabrook, Soren Gantt, Kieren A Marr, Stanley Martin, Fernanda P Silveira, Raymund R Razonable, Upton D Allen, Marilyn E Levi, G Marshall Lyon, Lorraine E Bell, Shirish Huprikar, Gopi Patel, Kevin S Gregg, Kenneth Pursell, Doug Helmersen, Kathleen G Julian, Kevin Shiley, Bartholomew Bono, Vikas R Dharnidharka, Gelareh Alavi, Jayant S Kalpoe, Shmuel Shoham, Gail E Reid, Atul Humar
Journal: The Lancet Infectious Diseases (2010)
Isolation and partial characterization of Fc gamma-binding proteins of human leukocytes.
Authors: A Kulczycki, L Solanki, L Cohen
Journal: Journal of Clinical Investigation (1981)

We isolated and partially characterized three Fc-binding macromolecules from human leukocytes. Mononuclear cells from normal individuals and from five patients with chronic lymphocytic leukemia and neutrophils from normal donors were surface radiolabeled by using 125I and lactoperoxidase. After detergent solubilization of the cells, Fc gamma-binding macromolecules were purified by repetitive affinity chromatography under a variety of conditions and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Three radiolabeled macromolecules were isolated that retained specific ability to bind to Fc fragments. A 52,000-64,000-mol wt macromolecule was isolated from normal mononuclear and polymorphonuclear cells. A 43,000-mol wt band was characteristic of mononuclear cells, particularly from patients with chronic lymphocytic leukemia. A 33,000-mol wt molecule could be obtained from normal leukocytes under conditions that suggest it might be a proteolytic fragment.
Evaluation of Diabetes and Cardiovascular Disease Print Patient Education Materials for Use With Low–Health Literate Populations
Authors: Felicia Hill-Briggs, Andrea S. Smith
Journal: Diabetes Care (2008)

Populations with the lowest literacy and health literacy in the U.S. are also among those disproportionately burdened by diabetes and its complications. Yet, suitability of publicly available diabetes and cardiovascular (CVD) patient education materials for these patients is not clear. We evaluated selected American Diabetes Association (ADA) and American Heart Association (AHA) print education materials for accessibility and usability characteristics.English-language, print patient education brochures addressing lifestyle/behavioral management of diabetes and CVD were obtained from the ADA (n = 21) and the AHA (n = 19). Materials were evaluated using 32 criteria, 23 addressing literacy demand and 9 addressing behavioral activation, compiled from authoritative sources on development of low-literacy consumer health information.Of the 32 criteria identified by two or more sources, ADA materials consistently met 11 (34%) and AHA materials consistently met 8 (25%). Criteria most frequently achieved were text case, use of cues (e.g., bullets) to emphasize key points, design of graphics/illustrations, some provision of "how to" information, and positive depiction of cultural images. The least consistently achieved criteria were reading grade, word usage (e.g., scientific jargon), sentence length, font size, line length, white space, visual organization, limited scope, clear and specific (e.g., step-by-step) behavioral recommendations, and demonstration of audience relevance and cultural appropriateness.Materials consistently met few criteria for usability by patients with low literacy, limited prior medical knowledge, and/or limited resource availability. Use of available criteria and methods for increasing reach of print education materials to these underserved patient populations is indicated.
Not All Aggressive Adult T-Cell Leukemia/Lymphoma Subtypes Are Created Equal
Authors: Jorge J. Castillo, Brady E. Beltran
Journal: Journal of Clinical Oncology (2012)

presentedwhatisprobablythelargeststudytoevaluateprognosticfactorsinpatientswithadult T-cell leukemia/lymphoma (ATLL) to date; the study includedmore than 800 patients. The proposed prognostic index (PI), calledATL-PI by the authors, consists of ﬁve adverse variables: stage III/IV,EasternCooperativeOncologyGroupperformancestatus0-1,age 70years,serumalbuminlevel 3.5g/dL,andsolubleinterleukin-2receptorlevel 20,000U/mL.Accordingtotheriskcategory,patientswithhigh-,intermediate-,andlow-riskdiseaseexperiencedamedianoverallsurvivaltimeof4.6,7,and16.2months,respectively.ATLL is a rare type of peripheral T-cell lymphoma (PTCL) thatdevelops in individuals with a chronic infection by the humanT-lymphotrophic virus type I. The epidemiology of ATLL, not surpris-ingly, mimics that of human T-lymphotrophic virus type I and affectsindividualslivinginspeciﬁcgeographicregionssuchasJapan,theCarib-bean,CentralandSouthAmerica,NorthernAfrica,andtheMiddleEast.Clinically,ATLLhasatleastfourvariants:acute(leukemic),lymphoma-tous,smoldering,andchronic.Classically,theacuteandlymphomatoussubtypeshavebeenassociatedwithaworseprognosis.However, there are speciﬁc distinctions between the acute andlymphomatous subtypes of ATLL. First, few studies have shown ge-netic and pathophysiologic heterogeneity within the aggressive vari-ants of ATLL. Oshiro et al
Primary refractory Hodgkin’s disease
Authors: S.J. Horning
Journal: Annals of Oncology (1998)

Primary refractory Hodgkin's disease may generally be defined as progression of disease during induction treatment or a partial or transient response (< 60 days) to induction therapy.Salvage chemotherapy is inadequate in this patient population; fewer than 10% of patients survive for 10 years or longer.Improved outcomes after failure of primary induction therapy have been reported with myeloablative therapy and autografting.The projected event-free survivals ranged from 18%-49% at four years.Highly selected patients may benefit from salvage radio-therapy, but this may be best accomplished in combination with transplantation.A number of strategies might be considered for increasing the cure rate for the small subset of patients with primary refractory Hodgkin's disease.Among these, identification of patients at high risk for induction failure and modifications of primary treatment to address this risk hold the greatest promise for success.
Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease‐based registry (PSOLAR)
Authors: A.B. Kimball, C. Leonardi, M. Stahle, W. Gulliver, M. Chevrier, S. Fakharzadeh, K. Goyal, S. Calabro, W. Langholff, A. Menter
Journal: British Journal of Dermatology (2014)

Psoriasis is associated with several comorbidities and behavioural risk factors.
Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy
Authors: Steven A. Rosenberg, James C. Yang, Richard M. Sherry, Udai S. Kammula, Marybeth S. Hughes, Giao Q. Phan, Deborah E. Citrin, Nicholas P. Restifo, Paul F. Robbins, John R. Wunderlich, Kathleen E. Morton, Carolyn M. Laurencot, Seth M. Steinberg, Donald E. White, Mark E. Dudley
Journal: Clinical Cancer Research (2011)

Most treatments for patients with metastatic melanoma have a low rate of complete regression and thus overall survival in these patients is poor. We investigated the ability of adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate durable complete regressions in heavily pretreated patients with metastatic melanoma.
The Circulation of the Fetus in Utero
Authors: ABRAHAM M. RUDOLPH, MICHAEL A. HEYMANN
Journal: Circulation Research (1967)

Techniques are described for insertion of vinyl catheters into the umbilical and limb vessels of the fetus of the sheep or the goat through small uterine incisions, with the ewes under spinal analgesia. The catheters are exteriorized and the fetus can be studied in its normal intrauterine environment. During constant infusion of antipyrine into a fetal limb vein, placental arteriovenous difference of antipyrine was measured, and fetal umbilical blood flow was calculated by the Fick method. "Carbonized" microspheres (50-µ diameter) labeled with various nuclides were injected into different venous sites in the fetus. The distribution pattern of the microspheres was used to determine the relative distribution of blood flow. Experimental evidence is provided that (1) there is no significant recirculation of microspheres, (2) the distribution of spheres is proportional to flow, and (3) circulatory physiology is not altered by injection of spheres. Quantitative data on the distribution of umbilical venous and superior and inferior vena caval return were obtained. It was possible to determine the actual blood flow to each of the fetal organs by relating the proportions of nuclide in each organ to that in the placenta. Total cardiac output was then calculable, taking into consideration the hemodynamic arrangement of the fetal circulation.
Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials
Authors: M. Sieniawski, T. Reineke, A. Josting, L. Nogova, K. Behringer, T. Halbsguth, M. Fuchs, V. Diehl, A. Engert
Journal: Annals of Oncology (2008)
Meckel's diverticulum
Authors: W G Donaldson
Journal: Journal of the Royal Society of Medicine (2007)

A review article should be complete to be authoritative. In the review by Sagar et al.1 (October 2006, JRSM), the authors suggest aspiring surgeons learn that a Meckel's diverticulum may present incidentally by haemorrhage, by intussusception or other forms of intestinal obstruction, by peptic ulceration, by involvement in a Littre's hernia or as an umbilical fistula or that it may undergo neoplastic change. It should be acknowledged that enterolith calculi arise in Meckel's diverticula.2,3 This uncommon complication of the congenital anomaly is not unique to Australia.

Also, in the interests of pedantry, the name of Fabricius Hildanus is thus, not as is written on page 502 of the review. Furthermore, the word melaena referring to dark tarry stools is also misspelt in the long uninterrupted paragraph on page 503 concerning diagnostic dilemmas.
Near-total human face transplantation for a severely disfigured patient in the USA
Authors: Maria Siemionow, Frank Papay, Daniel Alam, Steven Bernard, Risal Djohan, Chad Gordon, Mark Hendrickson, Robert Lohman, Bijan Eghtesad, Kathy Coffman, Eric Kodish, Carmen Paradis, Robin Avery, John Fung
Journal: The Lancet (2009)
The Impact of the Completed Human Genome Sequence on the Development of Novel Therapeutics for Human Disease
Authors: Christopher P. Austin
Journal: Annual Review of Medicine (2004)

With the official completion of the Human Genome Project in April 2003, we have both the opportunity and the imperative to translate this unprecedented scientific accomplishment into tangible improvements in human health. Medical benefits from the genome will come in stages and can be conceptualized as occurring in three areas: improved understanding of disease causation at the molecular level, improved diagnosis and disease classification based on genetic profiles, and new therapeutics based on targets identified in the genome. These improvements will require increased physician understanding of genetic principles applied to common diseases.