tbuckley/cabot-search huggingface dataset:
Abstract 2136: Expression of fusion proteins in acute myeloid leukemia cells increases sensitivity to histone deacetylase inhibitors
Authors: Luca A. Petruccelli, Kim L. Rice, Filippa Pettersson, Jessica N. Nichol, Sophia Skoulikas, Jonathan D. Licht, Wilson H. Miller
Journal: Cancer Research (2011)

Abstract Acute myeloid leukemias (AMLs) are often characterized by chromosomal translocations resulting in the expression of fusion proteins (FP). Some FP have been demonstrated to recruit histone deacetylases (HDACs) and repress the expression of DNA repair genes. This may result in an increased sensitivity to histone deacetylase inhibitors (HDI) due to their ability to also down-regulate DNA repair gene expression and induce DNA damage. We have tested the sensitivity of PLZF-RARα, PML-RARα and AML1-ETO inducible cell lines to HDI in order to characterize changes in the mechanisms of cell death. Treatment of U937 cells with vorinostat results in DNA damage as measured by the COMET assay, followed by cell death. To test the effect of FP expression, U937 cells stably transfected with PLZF-RARα, PML-RARα or AML1-ETO cDNA under the control of a tetracycline-off or a zinc-inducible system were treated with vorinostat and assayed for cell death in the presence/absence of FP. FP expression resulted in increased cell death and caspase-3/7 activation. This effect was found to be largely caspase driven as pre-treatment with the pan-caspase inhibitor Z-VAD-FMK resulted in protection against vorinostat-induced cell death. In addition, FP expressing cells were also exposed to the DNA-targeting agents Doxorubicin, Etoposide, Cisplatin and ionizing radiation. Again, FP expression resulted in increased cell death. In addition, we investigated the effect of FP expression on vorinostat sensitivity using a PLZF-RARα murine hematopoietic model. A retroviral expression system was used to overexpress PLZF-RARα in lineage-depleted (Lin-) murine hematopoietic progenitors, followed by vorinostat treatment in the absence/presence of PLZF-RARα. The increased sensitivity of FP expressing cells to HDI and DNA-targeting agents suggests a mechanism where the combination of an FP expression and HDI results in an increased accumulation of DNA damage, leading to enhanced cell death. These findings are significant as they point to FP expressing AMLs as a target group that may respond better to HDI-based therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2136. doi:10.1158/1538-7445.AM2011-2136
Familial Trends in Low Birth Weight
Authors: F. Johnstone, L. Inglis
Journal: BMJ (1974)

The reproductive performance of sisters and sisters-in-law of 185 women who had delivered “light-for-dates” and “premature expulsion” low birth weight infants was studied. Percentile birth weights were compared taking into account length of gestation, fetal sex, and the height, weight, parity, and smoking habits of the mother. Sisters of women who had delivered light-for-dates babies had lighter babies than the general population, their sisters-in-law, or the sisters of women in the premature expulsion group. These other groups, however, had the expected distribution of percentile birth weights. Data on familial trends in smoking habits and unknown gestation are also presented. The results are consistent with the theory that the mother9s own intrauterine experience affects her reproductive performance but could also be explained by shared family learning experience of as yet unidentified microsocial factors related to pregnancy performance.
Course of angina pectoris after an acute coronary event.
Authors: L E Daly, N Hickey, R Mulcahy
Journal: BMJ (1986)

The course of postcoronary angina pectoris was examined in 555 men who had survived a first attack of myocardial infarction or unstable angina. Patients were aged less than 60 and were followed up yearly for up to 17 years. Only 25 (4.5%) had coronary artery bypass surgery. Most patients with angina were treated by nitrates alone. One year after infarction 24.1% of survivors (124/515) reported the presence of angina pectoris, and the proportions at five, 10, and 15 years were 29.9%, 30.4%, and 43.5% respectively. Seventeen years after the initial event 35.3% of the survivors had never reported postcoronary anginal symptoms. The patients who experienced anginal symptoms in the year after their coronary attack had a poorer long term survival than the group who were symptom free over the first year. These patients also had longer subsequent periods with angina, though in 41.7% angina resolved before death after a median of 2.9 years. Throughout follow up mortality during periods in which patients experienced angina was higher than in the symptom free periods. This long term follow up study of patients after a coronary event confirms that the presence or absence of angina may vary considerably over time in patients treated medically and that the presence of angina is associated with a poorer prognosis. These findings have important implications when assessing the effects of various treatment modalities on postcoronary angina, including coronary artery bypass surgery.
Broca's area and language evolution
Authors: Andrew Carstairs-McCarthy
Journal: Behavioral and Brain Sciences (2000)

Grodzinsky associates Broca's area with three kinds of deficit, relating to articulation, comprehension (involving trace deletion), and production (involving “tree pruning”). Could these be special cases of one deficit? Evidence from research on language evolution suggests that they may all involve syllable structure or those aspects of syntax that evolved through exploiting the neural mechanisms underlying syllable structure.
Differential glycosaminoglycan expression and hyaluronan homeostasis in juvenile hyaline fibromatosis
Authors: Thrasivoulos G. Tzellos, Alexander Dionyssopoulos, Ioannis Klagas, George Karakiulakis, Lambis Lazaridis, Eleni Papakonstantinou
Journal: Journal of the American Academy of Dermatology (2009)
What Are Physicians For?
Authors: Ronald A. Carson
Journal: JAMA (1977)

To make this interaction (between doctor and patient) as productive as possible in terms of the relief of human suffering is the object of everything we do in medicine. 1   WHAT are physicians for? Does anyone know the answer to this question anymore? One reads and hears a variety of answers, from the very narrow to the extremely broad. Physicians, some argue, should attend to what they know best. The proper business of medicine is pathology, the diagnosis and treatment of disease. Others argue that disease must be seen contextually, as belonging to a whole human being who is a part of a web of relationships, who holds a certain job, has responsibilities, shares this belief system and not that, and so on. For the disease-oriented physician, this latter approach only clutters the mind and confuses the issue. For the advocate of the whole-man approach, focusing on disease alone is
Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria
Authors: Charles G. Bailey, Renae M. Ryan, Annora D. Thoeng, Cynthia Ng, Kara King, Jessica M. Vanslambrouck, Christiane Auray-Blais, Robert J. Vandenberg, Stefan Bröer, John E.J. Rasko
Journal: Journal of Clinical Investigation (2010)

Solute carrier family 1, member 1 (SLC1A1; also known as EAAT3 and EAAC1) is the major epithelial transporter of glutamate and aspartate in the kidneys and intestines of rodents. Within the brain, SLC1A1 serves as the predominant neuronal glutamate transporter and buffers the synaptic release of the excitatory neurotransmitter glutamate within the interneuronal synaptic cleft. Recent studies have also revealed that polymorphisms in SLC1A1 are associated with obsessive-compulsive disorder (OCD) in early-onset patient cohorts. Here we report that SLC1A1 mutations leading to substitution of arginine to tryptophan at position 445 (R445W) and deletion of isoleucine at position 395 (I395del) cause human dicarboxylic aminoaciduria, an autosomal recessive disorder of urinary glutamate and aspartate transport that can be associated with mental retardation. These mutations of conserved residues impeded or abrogated glutamate and cysteine transport by SLC1A1 and led to near-absent surface expression in a canine kidney cell line. These findings provide evidence that SLC1A1 is the major renal transporter of glutamate and aspartate in humans and implicate SLC1A1 in the pathogenesis of some neurological disorders.
Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes
Authors: T TATSUMI, J SHIRAISHI, N KEIRA, K AKASHI, A MANO, S YAMANAKA, S MATOBA, S FUSHIKI, H FLISS, M NAKAGAWA
Journal: Cardiovascular Research (2003)

Objectives: The present study examined the possibility that intracellular ATP levels dictate whether hypoxic cardiac myocytes die by apoptosis or necrosis. Background: Although apoptosis and necrosis may appear to be distinct forms of cell death, recent studies suggest that the two may represent different outcomes of a common pathway. In ischemic myocardium, apoptosis appears early, while energy stores are presumably still available, followed only later by necrosis. Methods: Neonatal rat cardiac myocytes were exposed to continuous hypoxia, during which the intracellular ATP concentration was modulated by varying the glucose content in the medium. The form of cell death was determined at the end of the hypoxic exposure. Results: Under total glucose deprivation, ATP dropped precipitously and cell death occurred exclusively by necrosis as determined by nuclear staining with ethidium homodimer-1 and smearing on DNA agarose gels. However, with increasing glucose concentrations (10, 20, 50, 100 mg/dl) cellular ATP increased correspondingly, and apoptosis progressively replaced necrosis until it became the sole form of cell death, as determined by nuclear morphology, DNA fragmentation on agarose gels, and caspase-3 activation. The data showed a significantly positive correlation between myocyte ATP content and the percentage of apoptotic cells. Hypoxia resulted in lactate production and cellular acidification which stimulates apoptosis. However, acidification-induced apoptosis was also increased in an ATP-dependent fashion. Loss of mitochondrial membrane potential and cytochrome c release from the mitochondria was observed in both the apoptotic and necrotic cells. Furthermore, translocation of Bax from cytosol into mitochondria preceded these events associated with mitochondrial permeability transition. Increased lactate production and a lack of effect by the mitochondrial inhibitor oligomycin indicated that ATP was generated exclusively through glycolysis. Conclusions: We demonstrate that ATP, generated through glycolysis, is a critical determinant of the form of cell death in hypoxic myocytes, independently of cellular acidification. Our data suggest that necrosis and apoptosis represent different outcomes of the same pathway. In the absence of ATP, necrosis prevails. However, the presence of ATP favors and promotes apoptosis.
Sildenafil as Treatment for Antidepressant-Induced Sexual Dysfunction—Reply
Authors: H. George Nurnberg
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Increased Expression of Protease-Activated Receptor-2 (PAR2) and PAR4 in Human Coronary Artery by Inflammatory Stimuli Unveils Endothelium-Dependent Relaxations to PAR2 and PAR4 Agonists
Authors: Justin R. Hamilton, Albert G. Frauman, Thomas M. Cocks
Journal: Circulation Research (2001)

Protease-activated receptor (PAR)1 and PAR2 are expressed on vascular endothelial cells and mediate endothelium-dependent relaxation in several species, and PAR4 agonists cause similar responses in rat aortas. To date, only PAR1 has been reported to mediate relaxation of human arteries despite endothelial cell expression of both PAR1 and PAR2 in these tissues. Because inflammatory stimuli increase PAR2 expression in human endothelial cells in culture, the present study investigated the effect of similar stimuli on PARs in human isolated coronary arteries (HCAs). In HCA ring segments suspended for isometric tension measurements, the selective PAR1-activating peptide, TFLLR (0.01 to 10 micromol/L), caused endothelium-dependent relaxation of precontracted preparations. Little or no change in vascular tension was elicited by either the PAR2- or PAR4-activating peptides, SLIGKV and GYPGQV, respectively (up to 100 micromol/L). Exposure of HCAs to interleukin (IL)-1alpha (1 ng/mL, 12 hours) or tumor necrosis factor-alpha (3 nmol/L, 12 hours) did not affect PAR1 expression but increased PAR2 and PAR4 mRNA levels by approximately 5- and 4-fold, respectively, as determined by quantitative polymerase chain reaction. Similar IL-1alpha treatment did not affect TFLLR-induced relaxations but revealed significant endothelium-dependent relaxations to SLIGKV (100 micromol/L, 61.4+/-6.7%) and GYPGQV (100 micromol/L, 34.8+/-6.4%). These studies are the first to demonstrate functional PAR2 and PAR4 in human arteries in situ. The selective upregulation of PAR2 and PAR4 expression and the increased vascular response in HCAs after exposure to inflammatory stimuli suggest a role for these endothelial receptors during inflammation.
Carcinoembryonic antigen (CEA) plasma levels in Michigan and Wisconsin dairy farmers.
Authors: H A Anderson, K D Rosenman, J Snyder
Journal: Environmental Health Perspectives (1978)

Carcionogenic embryonic antigen (CEA) titers were determined for 611 Michigan farmers exposed to PBB and a control nonexposed population of 139 Wisconsin farmers. The overall prevalence of elevated CEA titers was slightly higher in the Michigan study group, but the difference was not statistically significant. Smoking and/or significant past or present conditions (inflammatory bowel disease, ulcers, polyps, liver disease, chronic lung disease, or malignancies) were found to result in higher prevalence of elevated CEA titers, in both the Michigan study group and the Wisconsin control group, thus confirming previous reports. In addition, serum PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB may be additive to that of other factors which are known to result in an increased prevalence of elevated CEA titers is discussed.
Incidental Finding of Crossed Renal Ectopia Diagnosed on Bone Scan
Authors: DENNIS W. WULFECK, HOWARD S. SMITH, EDWARD B. SILBERSTEIN
Journal: Clinical Nuclear Medicine (1991)

A 78-Year-old man, with a history of gastric carcinoma with metastatic disease involving the left shoulder, had an incidental finding of crossed renal ectopia confirmed by CT and IVP.
Carcinoembryonic Antigen in Faeces
Authors: D. L. J. Freed, G. Taylor
Journal: BMJ (1972)

Carcinoembryonic antigen (C.E.A.) was detected in the faeces of 5 out of 10 healthy volunteers, 12 out of 18 patients suffering from gastrointestinal cancer (including 10 out of 11 cases of colonic cancer), and 3 out of 13 patients suffering from non-neoplastic disease. It is suggested that C.E.A. may be present in small amounts in normal faeces but that in malignant conditions of the bowel the amount increases.
Potential anti-inflammatory role of activin A in acute coronary syndromes
Authors: Camilla Smith, Arne Yndestad, Bente Halvorsen, Thor Ueland, Torgun Wæhre, Kari Otterdal, Hanne Scholz, Knut Endresen, Lars Gullestad, Stig S. Frøland, Jan Kristian Damås, Pål Aukrust
Journal: Journal of the American College of Cardiology (2004)
Including elderly people in clinical trials
Authors: J. Avorn
Journal: BMJ (1997)

Practitioners face a difficult paradox in prescribing for the elderly. Those aged over 65 comprise only about 14% of the population in most industrialised countries, yet they consume nearly a third of all drugs. Ample evidence indicates that, even in healthy elderly people, aging impairs the way the body handles drugs. In ill elderly people these changes can be exaggerated considerably.1

In an ideal world data from premarketing and postmarketing surveillance studies would describe how a given drug is likely to affect older patients differently from younger ones.2 Unfortunately, rather than being oversampled in clinical trials, to reflect their distribution in the drug consuming population, elderly people are inadequately represented.3 4 Moreover, when “old” patients are enrolled in trials, they are likely to be in their mid-60s and in quite good health. Nevertheless, we do not know to what extent “the elderly” …
The Proportion of Cases of AIDS Diagnosed in Outpatients
Authors: Kathryn J. Rauch
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In San Francisco, 98% of all cases of acquired immunodeficiency syndrome (AIDS) are reported to the Department of Public Health through a combination of active and passive surveillance of hospitals, clinics, and physicians, and 2% are reported through searches of death certificates. The passive surveillance system, which accounts for about 45% of reported cases, depends primarily on hospital-based infection control practitioners to report patients whose illness is diagnosed in hospitals. Since infection control practitioners are, typically, most familiar with inpatients, AIDS patients diagnosed in hospital outpatient departments may not be known to them and consequently may not be reported. In areas where there is less complete reporting of AIDS than in San Francisco, these cases may be a source of potential underreporting. To determine what proportion of AIDS cases is initially diagnosed in outpatients, we reviewed 200 consecutive AIDS cases reported to the Department of Public Health
Peutz-Jeghers syndrome with metastasizing duodenal carcinoma
Authors: J. P. Williams, A. Knudsen
Journal: Gut (1965)

EDITORIAL SYNOPSIS Since interest was first aroused in the Peutz-Jeghers syndrome there have been conflicting views as to the frequency with which malignant change occurs in the polyps found in the small intestine, and this has been due to the difficulty of interpreting the histological structure of the polypi.Many now feel that in this syndrome these lesions are hamartomas and that the apparent early malignant change is due to epithelial elements being caught up in the interlacing bands of smooth muscle.The case recorded here may well be the first fully documented example of carcinomatous change in a polyp in the Peutz-Jeghers syndrome, a metastasis having occurred in a regional lymph gland and the patient dying 15 months after the operation.A married white woman aged 52 was admitted to the LAPAROTOMY On 3 February an upper right paramedian West Middlesex Hospital on 27 January 1960 under the incision was made and subsequently extended to full 179 on
Moving Mental Health into the Disaster-Preparedness Spotlight
Authors: Katherine Yun, Nicole Lurie, Pamela S. Hyde
Journal: New England Journal of Medicine (2010)

As the Deepwater Horizon oil disaster enters its next phase, consensus is emerging that among its most profound immediate health effects are those on the emotional and psychosocial health of Gulf Coast communities. State mental health and substance-abuse agencies report an increase in emotional distress and demand for assistance. Calls to domestic-violence hotlines are increasing. Fishermen fear for their families' economic future, and communities wonder how the influx of clean-up workers and volunteers will affect their way of life. Most major disasters, including the Exxon Valdez spill, Hurricane Katrina, and the 9/11 attacks, have been followed by increases in the . . .
Principles and Techniques of Cardiac Pacing
Authors: John A. Callahan
Journal: JAMA (1971)

Topics related to early recognition and immediate care of cardiac emergencies have gained enormous popularity in the last decade. Many books, courses, articles, and lectures have dealt with this subject, although certainly not with equal excellence. Many of these presentations adopt an almost evangelistic viewpoint. Between the workers involved in developing techniques and equipment for the care of patients with cardiac disease, and their colleagues in medical practice, a gap quickly became established. Closing an information gap requires a kind of evangelism, and sometimes encounters resistance. Fortunately, resistance is disappearing, and the gap is now almost entirely one of lagging information exchange. Among the books which will succeed in disseminating information is Furman and Escher's rather short work on cardiac pacing. These authors have an almost journalistic approach to cardiac pacing, which at this point in its development lends itself to this kind of rhetorical treatment. The authors do not
AIDS Africa: Continent in Crisis; “Letting Them Die”: Why HIV/AIDS Prevention Programmes Fail
Authors: Justin O Parkhurst
Journal: BMJ (2004)

Helen Jackson Southern Africa HIV/AIDS Information Dissemination Services,$10 in Africa, $20 elsewhere, pp 440 ISBN 0 7974 2428 8 Email: info@safaids.org.zw http://www.safaids.org.zw/ Catherine Campbell James Currey, £12.95, pp 214 ISBN 0 85255 868 6 US edition:Indiana University Press, $22.95 ISBN 0 253 21635 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Readers of this journal will be aware of the tragic severity with which HIV and AIDS have affected the African continent. Yet people who study the disease will also be aware of the complexity involved in addressing the pandemic. Prevention, treatment, and care all require different approaches, involving social, clinical, and political interventions. There is no shortage of angles to take when addressing HIV and AIDS in Africa, yet Jackson's substantial tome tries to tackle them all. The book aims to be a general reference book on all manner of topics related to HIV and AIDS—although readers will note that … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Accumulation of 201TI-Chloride in a Parathyroid Adenoma
Authors: MASAO FUKUNAGA, RIKUSHI MORITA, YOSHIHARU YONEKURA, SHIGEHARU DOKOH, ITSUO YAMAMOTO, TORU FUJITA, KANJI TORIZUKA, JUICHI KAWAMURA
Journal: Clinical Nuclear Medicine (1979)

A 201TI-chloride scan was performed on a patient with primary hyperparathyroidism. 201TI-chloride accumulated in the region of the right lower thyroidal pole and a diagnosis of parathyroid adenoma was confirmed in traoperatively. 201TI-chloride imaging of a hyperfunctioning parathyroid gland seems to be useful for the detection and preoperative localization of a parathyroid adenoma.