tbuckley/cabot-search huggingface dataset:
The Safety of Irradiated Foods
Authors: George L. Tritsch
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In his Editorial entitled "How Safe Is the Food We Eat?" Dr DuPont<sup>1</sup>suggests: "One potentially important way to improve the microbiological safety of food is through irradiation. Ionizing radiation is a practical and safe means of reducing bacterial counts to an acceptable range." The price the consumer would pay for this reduction in bacterial counts is considerable. Irradiation of unsaturated fatty acids in foods produces peroxides that result in the formation of benzo(α)pyrene quinones,<sup>2</sup>a known and very potent group of carcinogens. This would be particularly ironic at a time when the American public is encouraged to increase consumption of unsaturated fatty acids to reduce the incidence of cardiovascular disease. Irradiation of carbohydrate results in formaldehyde, and quantitative studies<sup>3</sup>provide data that demonstrate that irradiation of 30 mg of sucrose produces 0.05 mg of formalde-hyde, which is readily detected as a mutagen in the
Association of Complement Factor H and LOC387715 Genotypes with Response of Exudative Age-Related Macular Degeneration to Intravitreal Bevacizumab
Authors: Milam A. Brantley, Amy M. Fang, Jennifer M. King, Asheesh Tewari, Steven M. Kymes, Alan Shiels
Journal: Ophthalmology (2007)
Rapidly Progressive Renal Failure in a Young Woman
Authors: Dante G. Scarpelli
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 35-year-old woman was referred to the hospital because of renal failure. She was well until three months previously, when mild hypertension was discovered and treated with a-methyldopa and a diuretic. Approximately two weeks before admission a nonproductive cough developed that was increased in the supine position, and dyspnea on exertion. Subsequently, she noticed increasing dyspnea and edema of the lower extremities. She was admitted to another hospital and was found to be hypertensive, azotemic, and in congestive heart failure. Bilateral retrograde pyelograms were normal, and she was transferred to the University of Kansas Medical Center.The . . .
A PROPOSED CLASSIFICATION OF IRITIS AND IRIDOCYCLITIS
Authors: LEE MASTEN FRANCIS
Journal: JAMA (1923)

The question may be asked with great propriety whether another classification of iritis and iridocyclitis is needed or even worthy of consideration. While it may be said that it is not demanded, yet some feel that it is desirable. This concerns, particularly, teachers, who are endeavoring to develop and drive home fundamental truths, but also clinicians, whose most difficult task is frequently diagnosis. Whatever contributes to orderly ways of thinking adds, not only to a better analysis of disease, but to more efficient treatment. Consequently, the subject should interest both teachers and practitioners. That there is more or less confusion, in the arrangement of uveal disease is evident from even a casual review of the various textbooks. That confusion should exist is quite natural because such correlations are the gradual outgrowth of the clinical manifestations of uveal disease as it has been observed since the beginning of medical time, rather
STUDIES ON SUSCEPTIBILITY TO INFECTION FOLLOWING IONIZING RADIATION
Authors: Lee E. Gordon, David Ruml, Helen Jo Hahne, C. Phillip Miller
Journal: The Journal of Experimental Medicine (1955)

In half of the normal mice examined, cultures of mesenteric lymph nodes were positive for enteric bacteria. When a non-pathogenic microorganism, Serratia marcescens, was established in the intestinal tract by administering it to mice in their drinking water, it, too, was recovered from the mesenteric lymph nodes of almost half of the normal mice examined. From these findings it was concluded that bacteria in small numbers were able to pass from the lumen of the unirradiated gut as far as the regional lymph glands. Such bacteria, except the pathogen, Salmonella, were rarely found in liver or spleen, never in the blood of the normal mice. After x-irradiation with 700 r, the incidence of positive cultures showed the liver or spleen became infected with enteric microorganisms before the blood stream was invaded. It appears, therefore, that these elements of the reticulo-endothelial system were able for a time to maintain the sterility of the blood after failure of the more immediate defenses against bacterial invasion from the intestinal tract. It is concluded that if any increased migration of bacteria through the intestinal mucosa resulted from the radiation injury, the increase must have occurred very soon after irradiation.
Australasian college of physicians sacks its ethics committee
Authors: D. Brill
Journal: BMJ (2013)

The Royal Australasian College of Physicians has sacked its own ethics committee just days after the committee produced strict new guidelines on doctors’ ties to industry.

The college has also provoked an outcry by refusing to release its guidelines for public consultation, opting for an internal process instead.

The draft Guidelines for Ethical Relationships Between Health Professionals and Industry had strengthened the already tough, pro-transparency stance of previous editions. Among its recommendations it labelled doctors’ use of drug samples and starter packs as “inappropriate,” it said, given that these were “primarily a marketing exercise.”

The draft guidance also explicitly called on …
REPORT OF COMMITEE ON GRADING LESIONS, COUNCIL ON ARTERIOSCLEROSIS, AMERICAN HEART ASSOCIATION
Authors: HENRY C. MCGILL, B. W. BROWN, IRA GORE, GARDNER C. McMILLAN, O. J. POLLAK, STANLEY ROBBINS, JAMES C. ROBERTS, ROBERT W. WISSLER
Journal: Circulation (1968)

A committee of pathologists compared four methods of evaluating coronary artery stenosis in the first 6 cm of 30 right coronary arteries. Seven judges twice estimated the percent reduction in lumen and the length of stenosed artery in longitudinally opened arteries, in postmortem angiograms, in casts, and in the three media together. The mean of 14 replicate estimates (seven judges, two rounds) based on the composite media was considered the "truest" value for each artery. Estimates based on casts correlated best with those based on the composite media. Estimates based on arteries and angiograms were consistently lower than those based on casts or on the composite media. Reliability was worst for estimates based on the arteries, intermediate for estimates based on angiograms and the composite media, and best for estimates based on casts. There was significant bias among judges in estimates based on single media, except in length stenosed based on arteries and angiograms. There was also significant bias among judges in both measures of stenosis based on the composite media. Percent reduction in lumen is correlated with length of artery stenosed. When more than half of the first 6 cm is stenosed, the lumen reduction approaches 100%. Either of the two measures, any one of the three single media, or any combination of the three media may be useful in evaluating coronary artery stenosis. Choice of the method depends on the requirements of the study. Artery, angiogram, and cast together seem indicated when clinicopathological correlation is the purpose of the investigation. An investigator must establish the reliability and validity of any method chosen under the conditions of his study.
Lung Cancer Trials Probe Effects of Maintenance Therapy, Targeted Agents
Authors: Tracy Hampton
Journal: JAMA (2009)

Research Institute at Harbor-UCLA Medical Center. “Current smokers also should carefully consider this mortality risk before beginning or continuing combined hormone therapy,” he added. These findings were in contrast to the results of most case-control studies that have not found an increased risk, according to Bruce Johnson, MD, director of the Lung Cancer Program at the Dana-Farber/Harvard Cancer Center, who was not involved in the research. “This [Women’s Health Initiative study] is likely more accurate since it is . . . a prospective randomized study,” he said. These latest findings may encourage additional studies on the effects of hormones on the development and progression of lung cancer. The investigators also hope that their results will prompt physicians and patients to reassess the use of combined hormone therapy for the treatment of menopausal symptoms.
A Hemoglobin Variant Associated with Neonatal Cyanosis and Anemia
Authors: Moira A. Crowley, Todd L. Mollan, Osheisa Y. Abdulmalik, Andrew D. Butler, Emily F. Goodwin, Arindam Sarkar, Catherine A. Stolle, Andrew J. Gow, John S. Olson, Mitchell J. Weiss
Journal: New England Journal of Medicine (2011)

Globin-gene mutations are a rare but important cause of cyanosis. We identified a missense mutation in the fetal Gγ-globin gene (HBG2) in a father and daughter with transient neonatal cyanosis and anemia. This new mutation modifies the ligand-binding pocket of fetal hemoglobin by means of two mechanisms. First, the relatively large side chain of methionine decreases both the affinity of oxygen for binding to the mutant hemoglobin subunit and the rate at which it does so. Second, the mutant methionine is converted to aspartic acid post-translationally, probably through oxidative mechanisms. The presence of this polar amino acid in the heme pocket is predicted to enhance hemoglobin denaturation, causing anemia.
Expression of delta F508 cystic fibrosis transmembrane conductance regulator protein and related chloride transport properties in the gallbladder epithelium from cystic fibrosis patients
Authors: Nathalie Dray-Charier, Annick Paul, Jean-Yves Scoazec, Danielle Veissière, Martine Mergey, Jacqueline Capeau, Olivier Soubrane, Chantal Housset
Journal: Hepatology (1999)

Currently, economic evaluation of new medical therapies is conducted routinely. Development of an analysis plan before performance of the analysis is a first step in the analysis of data from such evaluations. Univariate analysis of costs can be performed with both parametric and nonparametric tests. Potential multivariable analyses include ordinary least squares regression, nonparametric hazard models, parametric failure time models, Cox semiparametric regression, and joint distributions of survival and cost. In addition to developing point estimates for economic outcomes, 95% confidence intervals for cost-effectiveness ratios should be developed to evaluate the level of uncertainty that surrounds these estimates. Sensitivity analysis should be used to address other sources of uncertainty.
Abstract B52: The bromodomain inhibitor JQ1 enhances cisplatin-mediated cytotoxicity in ovarian cancer cells
Authors: Dineo Khabele, Andrew J. Wilson, Jeanette Saskowski, Scott W. Hiebert
Journal: Clinical Cancer Research (2013)

Abstract Ovarian cancer is the most lethal gynecologic malignancy. The treatment of platinum resistance disease remains an urgent and unmet clinical need. Identification of bromodomain inhibitors to disrupt “reading” of aberrant protein acetylation marks in cancer, leading to down-regulation of lineage-specific oncogenes is an exciting development in epigenetic drug therapy. The oncogenic transcription factor c-MYC (MYC) is amplified in approximately 30-40% of high grade serous ovarian tumors and may be epigenetically deregulated via a “super enhancer” on chromosome 8q24. JQ1, an inhibitor of bromodomain binding, down-regulates MYC expression in MYC-amplified tumors. However, this mechanism appears to be tissue-specific and has not been tested as a method for chemosensitization in ovarian cancer. We hypothesized that JQ1 could be used to enhance cisplatin cytotoxicity in ovarian cancer cells, in part by repression of MYC. Ovarian cancer cell lines were selected after in silico evaluation of publically available, annotated cell line collections. Cell lines with relatively low expression of MYC (IGROV-1 and SKOV3) and relatively high expression, A2780 parental [A2780PAR] and isogenic cisplatin-resistant A2780CP20 cells) were treated with 0.1% DMSO, JQ1, cisplatin or the combination of drugs. Sulforhodamine B (SRB) and clonogenic assays were used to assess effects on cell viability. Apoptosis was evaluated by Western Blot detection of cleaved PARP. Expression of MYC was measured by QPCR and Western Blot. JQ1 reduced cell viability and clonogenicity at sub-micromolar concentrations in the ovarian cancer cell lines examined. Furthermore, JQ1 treatment sensitized ovarian cancer cells, including the resistant A2780CP20, to the growth inhibitory and pro-apoptotic effects of cisplatin. However, the cytotoxic effects of JQ1 were not directly correlated with down-regulation of MYC. First, A2780PAR and A2780CP20 cells expressed the highest basal levels of MYC in our panel, but were not the most sensitive to JQ1-induced anti-tumor effects. Second, JQ1 markedly inhibited MYC expression in A2780PAR, but not A2780CP20 cells, despite relatively similar reduction in growth inhibition by JQ1 alone and combined with cisplatin in these cell lines. Taken together, these novel findings suggest that JQ1 could be used to sensitize ovarian cancer cells to platinum-based therapy. Identifying oncogenic targets of JQ1 other than MYC in ovarian cancer is a priority for further development of bromodomain inhibitors in ovarian cancer. Citation Format: Dineo Khabele, Andrew J. Wilson, Jeanette Saskowski, Scott W. Hiebert. The bromodomain inhibitor JQ1 enhances cisplatin-mediated cytotoxicity in ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B52.
CD8+CD60+ TCR α/β+CD45RO+ T Cells and CD4+ T cells are required for induction of human ragweed specific memory IgE responses
Authors: T.A. Smith-Norowitz, K.B. Norowitz, M.H. Bluth, S. Chice, R.O. Joks, K. Liao, M. Nowakowski, H.G. Durkin
Journal: Journal of Allergy and Clinical Immunology (2005)
Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction.
Authors: R C Harris, J A McKanna, Y Akai, H R Jacobson, R N Dubois, M D Breyer
Journal: Journal of Clinical Investigation (1994)

The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption. Two separate isoforms of cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded by a 2.8-kb mRNA, and mitogen-activated COX-2, encoded by a 4.0-4.5-kb mRNA. COX-2 expression increases during development and inflammation, but, except for brain, constitutive expression is low. It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX-1. However, in the absence of inflammation, low levels of COX-2 mRNA are also detectable in the kidney. To examine the role of COX-2 in the kidney and determine its intrarenal localization, we used a 1.3-kb cDNA probe specific for the 3' untranslated region of rat COX-2 and COX-2-specific antiserum. The COX-2-specific cDNA probe hybridized with a 4.4-kb transcript in total RNA from adult rat kidney. Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations. In situ hybridization and immunohistochemistry indicated that renal cortical COX-2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle. In addition, COX-2 immunoreactivity was detected in interstitial cells in the papilla. No COX-2 message or immunoreactive protein was detected in arterioles, glomeruli, or cortical or medullary collecting ducts. When animals were chronically sodium restricted, the level of COX-2 in the region of the macula densa increased threefold (from 0.86 +/- 0.08 to 2.52 +/- 0.43/mm2) and the total area of the COX-2 immunoreactive cells in cortex increased from 34 microns2/mm2 of cortex to 226 microns2/mm2 of cortex. The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis.
Selected Self-Help: A Study of Clients of a Community Social Psychiatry Service
Authors: STANLEY LEHMANN
Journal: American Journal of Psychiatry (1970)

Three storefront neighborhood service centers were set up to serve a disadvantaged area in New York City as part of a community psychiatric service. The first two years of their full operation are assessed in terms of who used the centers and why. Clients of the centers were interviewed some time after their visits and compared with the rest of the community. The author found that the people in the community with the most problems are most likely to use the centers, and the problems they bring are typical of those in the community. Psychiatric problems are seldom presented expressly, but people with histories of psychiatric illness are much more likely to visit the centers.
324 COMPARISON OF DIAGNOSTIC ALGORITHMS FOR LIVER FIBROSIS IN HEPATITIS C. NEW ALGORITHMS ARE AS EFFECTIVE WHILE MORE PRECISE AND TOTALLY NON-INVASIVE
Authors: J. Boursier, V. de Ledinghen, J.-P. Zarski, I. Fouchard-Hubert, M.-C. Rousselet, Y. Gallois, F. Oberti, P. Calès
Journal: Journal of Hepatology (2011)
Textbook of Interventional Cardiology, vols 1 &amp; 2
Authors: Allan Schwartz
Journal: JAMA (1994)

The second edition of<i>Textbook of Interventional Cardiology</i>, edited by Eric J. Topol, MD, is a comprehensive, multiauthored work that presents the cognitive basis for contemporary percutaneous catheter-based therapies for cardiac and vascular disease. The emphasis is appropriately on the management of patients with coronary and valvular heart disease. The book has expanded to two volumes since the first edition, published in 1989. This is a reflection of the rapid growth in knowledge of the clinical and biologic effects of current and emerging interventional techniques. It is also a reflection of the editor's broad definition of the areas that belong in the knowledge base of an interventional cardiologist. The book does not provide instruction in the performance of procedures but rather focuses on procedural indications, outcomes, and related clinical and biologic issues. In this spirit, the first eight chapters are devoted to drug therapies that are used adjunctively or alternatively
Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient.
Authors: D Phaneuf, M Lambert, R Laframboise, G Mitchell, F Lettre, R M Tanguay
Journal: Journal of Clinical Investigation (1992)

Type 1 hereditary tyrosinemia (HT1) is a metabolic disorder caused by a deficiency of fumarylacetoacetate hydrolase (FAH). Using a full-length FAH cDNA and specific antibodies, we investigated liver specimens from seven unrelated HT1 patients (six of French Canadian and one of Scandinavian origin). The expression of FAH in livers of these individuals was analyzed at several molecular levels including mRNA, immunoreactive material (IRM), and enzymatic activity. Four phenotypic variants were differentiated by these assays: (i) presence of FAH mRNA without any IRM or enzymatic activity, (ii) decreased FAH mRNA, IRM, and enzymatic activity, (iii) moderately decreased FAH mRNA and IRM with severely reduced enzymatic activity, and (iv) undetectable FAH mRNA, IRM, and enzymatic activity. These various molecular phenotypes suggest that this disorder may be caused by a variety of FAH mutations. Interestingly, we found no apparent relationship between the clinical and the molecular phenotypes, except that patients with absent IRM and enzymatic activity tend to have higher levels of serum alpha-fetoprotein and an earlier clinical onset. To further analyze the molecular basis of HT1, the FAH cDNA of a patient designated as variant A was amplified and sequenced. An A-to-T transversion, which substitutes asparagine16 with isoleucine (N16I), was identified. This patient was heterozygous as shown by direct sequencing of the amplified region and hybridization with allele-specific oligonucleotide probes. The N16I allele originates from the father and the second allele appears not to be expressed in the liver of the proband. CV-1 cells transfected with the mutant cDNA produced FAH mRNA, but no protein or hydrolytic activity, as predicted by the "A" phenotype of the patient. This is the first demonstration of heterogeneity in the expression of FAH at the levels of protein, mRNA, and enzymatic activity in the livers of HT1 patients and is the first identification of a causal mutationin this disease.
Impaired antipneumococcal antibody production in patients without spleens.
Authors: F Di Padova, M Durig, F Harder, C Di Padova, C Zanussi
Journal: BMJ (1985)

Fifteen splenectomised and 15 normal subjects were studied, in absence of any intentional immunisation, for pokeweed mitogen induced synthesis of antipneumococcal capsular polysaccharide antibodies in vitro by peripheral blood mononuclear cells. Results showed that removal of the spleen had caused a persistent immune deficiency of circulating B cells capable of synthesising IgM antipneumococcal capsular polysaccharide. In vitro synthesis of polyclonal IgM and IgG by peripheral blood mononuclear cells of subjects without spleens was also depressed. These defects were due to an abnormality of the B cell compartment. These data are evidence of the major role of the spleen in the control and production of a consistent part of pokeweed mitogen responsive circulating B cells and add another facet to the complex immune dysfunction of splenectomised subjects. The findings, moreover, may help in understanding the susceptibility of splenectomised people to pneumococcal sepsis and the delayed and impaired antibody response to pneumococcal vaccine.