tbuckley/cabot-search huggingface dataset:
Abstract 4609: Epigenetic regulation of BRM
Authors: Bhaskar Kahali, Sarah Gramling, David N. Reisman
Journal: Cancer Research (2012)

Abstract BRM is part of the SWI/SNF complex and is key anticancer protein which is silenced in variety of tumor types. SWI/SNF is a prerequisite for the function of many different anticancer proteins such as Rb and p53 and it has essential roles in growth control, differentiation, development, cell adhesion, and DNA repair. Consequently, inactivation or impairment of this complex can stimulate tumor development and tumor progression through the abrogation of a number of anticancer mechanisms. Unlike many tumor suppressor proteins, BRM is not mutated, but rather epigenetically suppressed, which is validated by the fact that HDAC inhibitors were the first compounds found to restore BRM expression. Unfortunately, these compounds are too broadly active and in addition to restoring BRM expression, they inactivate it by acetylation. To try to better understand how BRM is epigenetically regulated, we knocked-out each of the known 11 HDACs, using shRNAs in BRM-deficient and BRM-positive cell lines to determine which ones regulate or inactivate BRM. We found that that shRNA knockdown of only HDAC3 or HDAC9 restores both BRM expression and function, while suppression of HDAC2 induces BRM acetylation. Similarly, we tested the impact of over-expression of 25 different Histone Acetyltransferases (HATs) on BRM expression and acetylation. We found ectopic expression of KAT6A, KAT6B, and KAT7 in BRM-deficient cell lines induces BRM whereas ectopic expression of KAT2B and KAT8 causes BRM acetylation in BRM-positive cell lines. We also uncovered that HDAC9 is greatly over-expressed only in BRM-deficient cell lines and its expression is driven by MEF2D and GATA3. Expression and knockdown experiments directed at MEF2D and GATA3 showed that these transcription factors regulate BRM and HDAC9. Similarly, we found that GATA3 expression is only expressed in BRM-deficient cell lines. This work outlines the complex array of proteins which are tied to the expression and regulation of BRM. It is important to note this epigenetic mechanism is not likely specific to BRM, but rather likely regulates a cadre of anticancer and cellular proteins as well. Hence, determining how BRM is aberrantly regulated is the first step in determining how to target BRM and this mechanism for therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4609. doi:1538-7445.AM2012-4609
Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World
Authors: J.A.L. Lindoso, R.N. Barbosa, M.P. Posada-Vergara, M.I.S. Duarte, L.K. Oyafuso, V.S. Amato, H. Goto
Journal: British Journal of Dermatology (2009)

Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized.To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV).Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes.Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm(-3) (range 8-258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti-Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti-Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection.Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm(-3)).
Alim-Louis Benabid and Mahlon DeLong win the 2014 Lasker~DeBakey Clinical Medical Research Award
Authors: Sarah Jackson
Journal: Journal of Clinical Investigation (2014)

The 2014 Lasker~DeBakey Clinical Medical Research Award recognizes the extraordinary efforts of two physician-scientists, Alim-Louis Benabid and Mahlon DeLong, whose combined work paved the way for the clinical use of deep brain stimulation to treat Parkinson’s disease (Figure ​(Figure1).1). Alim-Louis Benabid, a neurosurgeon at the University Hospital of Grenoble, France, pioneered the concept that high-frequency electrical stimulation in the brain could effectively treat tremors in patients. Neurologist Mahlon DeLong’s research provided the first roadmap of the circuitry of the basal ganglia, a set of structures beneath the cerebral hemispheres, and showed that a portion of the subthalamic nucleus is critically involved in relaying signals that influence movement. Their groundbreaking observations led to the development of deep brain stimulation of the subthalamic nucleus to treat dyskinesia in Parkinson’s disease patients. 



Figure 1

The recipients of the 2014 Lasker~DeBakey Clinical Medical Research Award. 



Parkinson’s disease is a progressive neurodegenerative disorder characterized by movement abnormalities that are triggered by the loss of dopamine-producing cells in a region of the midbrain known as the substantial nigra. Patients experience a range of symptoms including tremor, rigidity, difficulty in initiating movement, and slowness of movement (bradykinesia). While treatment with levodopa, a precursor of dopamine, can ameliorate symptoms, the medication itself may cause involuntary movements (dyskinesias) and motor fluctuation in patients as the disease progresses. Based on the work of Mahlon Delong and others in the field, we now know that several of the symptoms of Parkinson’s disease are caused by abnormal activity of neurons in the motor pathways of the basal ganglia, including the subthalamic nucleus. This understanding, coupled with the high-frequency deep brain stimulation technique that was developed by Alim-Louis Benabid, provided a new clinical approach that can dramatically improve the quality of life for Parkinson’s disease patients.
Ammonia production by isolated mouse proximal tubules perfused in vitro. Effect of metabolic acidosis.
Authors: G T Nagami, C M Sonu, K Kurokawa
Journal: Journal of Clinical Investigation (1986)

We examined the effects of metabolic acidosis in vivo and reduced bath and luminal pH in vitro on total NH3 (NH3 + NH+4) production rates by isolated mouse proximal tubule segments. Midproximal tubule segments were obtained from mice with NH4Cl-induced metabolic acidosis and from nonacidotic controls. The segments were perfused with modified Krebs-Ringer bicarbonate (KRB) buffer, incubated in KRB buffer containing 0.5 mM L-glutamine and 1.0 mM sodium acetate, and gassed with 95% O2 and 5% CO2. Isolated unperfused and perfused proximal tubules from acidotic mice produced total NH3 at higher rates than corresponding tubules from nonacidotic mice. Perfusion of the tubular lumen stimulated total NH3 production by tubules from both acidotic and nonacidotic mice. In contrast, lowering the bath pH to 7.0 by lowering the HCO3- concentration increased total NH3 production rates by tubules from nonacidotic mice but not by tubules from acidotic mice. Reducing the HCO3- concentration of the bath buffer to 10 mM while maintaining a pH of 7.4 had no significant effect on total NH3 production by tubules from nonacidotic mice. Lowering the luminal fluid pH by reducing the perfusate HCO-3 from 25 mM to 10, 5, or 1.2 mM while maintaining a bath pH of 7.4 lowered collected luminal fluid pH but had no effect on total NH3 production by proximal tubules from nonacidotic mice. These observations demonstrated that metabolic acidosis in vivo stimulated total NH3 production in isolated mouse proximal tubule segments and that low peritubular pH and HCO-3 stimulated total NH3 production by proximal tubule segments from nonacidotic mice in vitro.
775. Substrate-Mediated DNA Delivery for Neural Tissue Engineering
Authors: Tiffany L. Houchin, Jae-Hyung Jang, Lonnie D. Shea
Journal: Molecular Therapy (2005)

Tissue engineering scaffolds capable of efficient gene delivery can provide versatile systems to stimulate and direct tissue formation. In spinal cord repair, numerous strategies focus on axon regeneration. However, successful extension of axons throughout the injury site and into the distal spinal cord has been limited, as complete regeneration of axons requires both long term growth and guidance to the target. Several factors, including physical barriers and gradients of neurotrophic factors have been shown to direct axon extension. We hypothesize that a tissue engineering scaffold with sustained and patterned gene delivery of neurotrophic factors to cells (e.g., fibroblasts) cultured inside the scaffold will promote axonal outgrowth and regeneration. We have developed a process in which DNA complexes are immobilized to a surface for delivery to cells that are cultured on the substrate, a process termed substrate-mediated delivery. By increasing the concentration of DNA within the cellular microenvironment mass transport limitations associated with DNA delivery can be overcome to enhance transgene expression. Additionally, substrate-mediated gene delivery presents the opportunity to spatially control the location of immobilized DNA complexes inside a tissue engineering scaffold to attain patterns of transfected cells.
Is Crohn's disease due to defective immunity?
Authors: J R Korzenik
Journal: Gut (2006)

The understanding of the pathophysiology of Crohn’s disease is currently undergoing a reassessment. The concept of this disease as a primary T cell disorder is being questioned, with a new emphasis on the role of innate immunity in initiating early events and in perpetuating the inflammatory state. Crohn’s disease has been proposed instead to result from impaired innate immunity, encompassing the mucosal barrier and cellular elements including neutrophils and macrophages. Recent advances in genetics, functional studies on innate immunity and therapeutic trials on patients with Crohn’s disease have lent support to this evolving hypothesis.
The Practice Nurse--A New Look
Authors: J. W. Smith, J. B. O'Donovan
Journal: BMJ (1970)

A nurse has been employed by three general practitioners in a semi-rural practice of 9,000 patients since April 1968. Of her 1,360 home visits, 838 were primary visits, of which only 87 required follow-up by the doctor and 484 were requested directly to the nurse. More advanced procedures carried out by the nurse included electrocardiography, pregnancy diagnosis, blood sampling, and cytology. This study suggests that the work of a practice nurse improves the medical service already provided and reduces the work-load of the doctors, particularly by primary screening by the nurse both at home and in the surgery.
Inflammation at the neo squamo- columnar junction in Barrett's oesophagus
Authors: R C FITZGERALD
Journal: Gut (2000)

Editor,—In the recent article entitled “Inflammation of the gastro-oesophageal junction (carditis) in patients with symptomatic gastro-oesophageal reflux disease: a prospective study” ( Gut 1999; 45 :484–488), the authors determined that mucosal injury at the gastric cardia is highly localised to the region adjacent to the squamo-columnar junction in patients with gastro-oesophageal reflux disease (GORD). …
Enhanced efficacy of IL-15-based ALT-803 superagonist complex in combination with immune checkpoint inhibitors in hematologic and metastatic mouse tumor models
Authors: Wenxin Xu, Warren D Marcus, Peter R Rhode, Hing C Wong
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Recent advances in achieving highly durable clinical responses via inhibition of immune checkpoint molecules have revolutionized the outlook for cancer immunotherapy. However, such responses are only observed in a minority of patients, suggesting that strategies to further augment
TOPICAL TRIAMCINOLONE IN ECZEMA.
Authors: C. F. H. VICKERS, S. M. TIGHE
Journal: British Journal of Dermatology (1960)

Journal Article TOPICAL TRIAMCINOLONE IN ECZEMA. Get access C. F. H. VICKERS, M.B., M.R.C.P., M.R.C.P.E., C. F. H. VICKERS, M.B., M.R.C.P., M.R.C.P.E. Senior Registrar The Rupert Hallam Department of Dermatology, Sheffield Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar S. M. TIGHE, MB., M.R.C.P., D.C.H. S. M. TIGHE, MB., M.R.C.P., D.C.H. Registrar The Rupert Hallam Department of Dermatology, Sheffield Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 10, 1 October 1960, Pages 352–354, https://doi.org/10.1111/j.1365-2133.1960.tb13818.x Published: 01 October 1960
Consent to the publication of patient information: More on confidentiality and case material
Authors: Heather Draper, Wendy Rogers
Journal: BMJ (2004)

EDITOR—We welcome the views of the BMJ ethics committee.1 In an article for the Journal of Medical Ethics we drew attention to some of the obstacles to gaining consent for publication of case material in ethics.2 We also reviewed the policy of several general medical and specialist ethics journals and found that many, including the Journal of Medical Ethics , gave no instructions on confidentiality.

Given the amount of case material that is used in medical ethics, this is a …
Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay
Authors: Madhukar Pai, Rajnish Joshi, Sandeep Dogra, Deepak K. Mendiratta, Pratibha Narang, Shriprakash Kalantri, Arthur L. Reingold, John M. Colford, Lee W. Riley, Dick Menzies
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Although interferon-gamma (IFN-gamma) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown.To compare TST and IFN-gamma conversions and reversions in healthcare workers.We prospectively followed-up 216 medical and nursing students in India who underwent baseline and repeat testing (after 18 mo) with TST and QuantiFERON-TB Gold In-Tube (QFT). TST conversions were defined as reactions greater than or equal to 10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline IFN-gamma less than 0.35 and follow-up IFN-gamma greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-gamma greater than or equal to 0.35 and follow-up IFN-gamma less than 0.35 IU/ml.Of the 216 participants, 48 (22%) were TST-positive, and 38 (18%) were QFT-positive at baseline. Among 147 participants with concordant baseline negative results, TST conversions occurred in 14 (9.5%; 95% confidence interval [CI] = 5.3-15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI = 1.5-8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI = 6.9-17.9) using the definition of IFN-gamma greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI = 3.8-13.0) using IFN-gamma greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (>or= 0.70 IU/ml) was 96% (kappa = 0.70). QFT reversions occurred in 2/28 participants (7%) with baseline concordant positive results, as compared with 7/10 participants (70%) with baseline discordant results (p < 0.001).IFN-gamma assay shows promise for serial testing, but repeat results need to be interpreted carefully. To meaningfully interpret serial results, the optimal thresholds to distinguish new infections from nonspecific variations must be determined.
Who should be liable for funding recombinant factor VIII?
Authors: R. G Richards
Journal: BMJ (1998)

EDITOR—On 26 February the Department of Health announced that, acting on advice from the Committee on the Safety of Medicines, it will inform health authorities of “arrangements to ensure that recombinant factor VIII is made available to those [haemophiliac] children under the age of 16 who are not already receiving it, and to new patients.”1 This policy is a response to the perceived threat from blood products contaminated with the new variant Creutzfeldt-Jakob disease prion. This threat is largely theoretical,1-3 although many …
Incidence of repeated legal abortion.
Authors: C Brewer, R Howard
Journal: BMJ (1976)

The British Pregnancy Advisory Service (BPAS) reported on the repeat abortion rate in 4579 consecutive patients attending 4 BPAS branches during the first 6 months of 1976. 430 (9.4%) gave a history of 1 previous abortion, .3% of 2 abortions, .1% of 3 abortions; and 1 patient with 4 abortions. While 2nd abortions occur with some volume, multiple abortions are relatively rare. The characteristics of those patients having repeat abortions was similar to the characteristics of the sample as a whole. 16. 7% were housewives, 8.9% were students, and 7.6% were nurses. The majority of 2nd abortions took place in the 20-24 and 25-29 age groups.
The NLRP12 Inflammasome Recognizes Yersinia pestis
Authors: Gregory I. Vladimer, Dan Weng, Sara W. Montminy Paquette, Sivapriya Kailasan Vanaja, Vijay A.K. Rathinam, Marie Hjelmseth Aune, Joseph E. Conlon, Joseph J. Burbage, Megan K. Proulx, Qin Liu, George Reed, Joan C. Mecsas, Yoichiro Iwakura, John Bertin, Jon D. Goguen, Katherine A. Fitzgerald, Egil Lien
Journal: Immunity (2012)
Patterns of Professional Education
Authors: Glen R. Shepherd
Journal: JAMA (1960)

In the present climate of critical reappraisal of education in the United States, a currently accurate and objective comparison of education for the various professions could well provide useful information for members and educators of each profession. This book represents such an attempt It presents a comparative study of architecture, business administration, engineering, law, medicine, nursing, psychology, social work, teacher education, and veterinary medicine. The book is organized to compare the 10 fields in terms of the aims and objectives of curriculum; methods of instruction; faculty; recruitment and selection of students; relations between the professional school and the university; accrediting; and instruction in professional ethics. A total of 354 references are listed, only 184 of which are cited in the text. None refer to previous publications by the author. The book contains a prosaic presentation of cursory information about the 10 fields largely without value judgments and with analysis and
Immunopathology: hypersensitivity to 'boardomania'
Authors: D. Loi
Journal: JAMA (1978)

To the Editor.—  We read with interest the COMMENTARY on immunopathology by Thomas J. Gill III, MD, and Peter A. Ward, MD, two eminent immuno-pathologists whose contribution to this field is well recognized. While we could not agree with them more on the importance of immunopathology in modern medicine, we disagree with their statement that is, in fact, the essence of their article: ... certification... in immunopathology... is justified on the basis of current and future needs... One might ask what needs and whose needs: the need of some physicians to exhibit a nicely framed certificate in their office? the need of new laboratory tests in hospitals? Will this latter need be satisfied by a certification for special competence in immunopathology? It should be pointed out that important work was accomplished by people not certified by any boards (among these are some of the names quoted by Drs Gill and Ward).
Unhealthy Charities: Hazardous to Your Health and Wealth
Authors: David H. Mark
Journal: JAMA (1994)

This sometimes on-target but largely off-target book seeks to discredit the major health charities such as the American Heart Association, American Lung Association, and American Cancer Society. If the authors are to be believed, because of the health charities, scientific progress in cancer research has been impeded, fortunes have been siphoned off for personal gain, and the public is a dazed, confused, hypochondriac horde. The authors present some powerful facts, which we should all seriously examine. The major health charities support educational programs for health professionals and public education of sometimes dubious quality, which the authors rightly suggest is often thinly veiled fund-raising. Other expenditures include items such as buildings, automobiles, endowment investment, and savings for future programs. The authors' viewpoint is that all such expenditures are improper. They believe health charities should function in a continuous "war mentality" and spend every dollar as though it were the last. They
Detection of genetic effects of environmental agents.
Authors: E A Murphy
Journal: Environmental Health Perspectives (1981)

The fundamental problems in population monitoring for genetic effects are twofold: the binomialized nature of the data and the lower power due to small risk of finding positive results. The binomial character is artificial, even forced, and can with advantage be replaced by more refined analysis, and by a focus on all mutations, not merely harmful ones. Moreover, a binomial treatment ignores accessory information (birth order, clustering, etc.). But this objective requires that an explicit model be used instead of nonparametric methods; a cancer may represent multiple independent hits that should be separately scored; sequencing of a codon or its product may show multiple distinct changes.