tbuckley/cabot-search huggingface dataset:
Database development in toxicogenomics: issues and efforts.
Authors: William B Mattes, Syril D Pettit, Susanna-Assunta Sansone, Pierre R Bushel, Michael D Waters
Journal: Environmental Health Perspectives (2004)

The marriage of toxicology and genomics has created not only opportunities but also novel informatics challenges. As with the larger field of gene expression analysis, toxicogenomics faces the problems of probe annotation and data comparison across different array platforms. Toxicogenomics studies are generally built on standard toxicology studies generating biological end point data, and as such, one goal of toxicogenomics is to detect relationships between changes in gene expression and in those biological parameters. These challenges are best addressed through data collection into a well-designed toxicogenomics database. A successful publicly accessible toxicogenomics database will serve as a repository for data sharing and as a resource for analysis, data mining, and discussion. It will offer a vehicle for harmonizing nomenclature and analytical approaches and serve as a reference for regulatory organizations to evaluate toxicogenomics data submitted as part of registrations. Such a database would capture the experimental context of in vivo studies with great fidelity such that the dynamics of the dose response could be probed statistically with confidence. This review presents the collaborative efforts between the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress, the International Life Sciences Institute Health and Environmental Science Institute, and the National Institute of Environmental Health Sciences National Center for Toxigenomics Chemical Effects in Biological Systems knowledge base. The goal of this collaboration is to establish public infrastructure on an international scale and examine other developments aimed at establishing toxicogenomics databases. In this review we discuss several issues common to such databases: the requirement for identifying minimal descriptors to represent the experiment, the demand for standardizing data storage and exchange formats, the challenge of creating standardized nomenclature and ontologies to describe biological data, the technical problems involved in data upload, the necessity of defining parameters that assess and record data quality, and the development of standardized analytical approaches.
Echographic assessment of atrial transport, mitral movement, and ventricular performance following electroversion of supraventricular arrhythmias.
Authors: A N DeMaria, J E Lies, J F King, R R Miller, E A Amsterdam, D T Mason
Journal: Circulation (1975)

Controversy attends the extent and temporal sequence of improvements in hemodynamic function resulting from the return of atrial contraction following cardioversion of supraventricular arrhythmias. Thus, mitral, left atrial (LA) and left ventricular (LV) echograms were obtained before and one hour after conversion of supraventricular arrhythmias to normal sinus rhythm by direct current countershock in patients with chronic coronary disease or cardiomyopathies without valvular dysfunction. The duration of the rhythm disturbance varied from one day to five years in 22 patients and was indeterminate in 13. Atrial systole immediately produced prominent mitral "A" waves with anterior valve excursion of 7.5 mm (range 3 to 12) in 33 of the 35 patients (94%). The two patients with atrial electromechanical dissociation reverted to atrial fibrillation within one week. Cardioversion caused a decline in LA diameter (3.5 to 3.2 cm, P less than .001) and a rise in LV end-diastolic dimension (5.2 to 5.5 cm, P less than .001) while LV end-systolic dimension was unchanged (4.2 cm). Thereby stroke volume rose. Heart rate fell an average of 16 beats/min. Depressed cardiac output was improved + 0.84 L/min/m-2. Thus, in the majority of patients with acute or chronic supraventricular arrhythmias without mitral valve disease, cardioversion promptly restores effective atrial contraction, decreases LA size, and results in substantial hemodynamic benefit.
A Quick Fix?
Authors: Florian P. Limbourg
Journal: Circulation (2012)

A utologous cell therapy with bone marrow (BM)-derived proangiogenic cells is a promising new treatment modality to enhance ischemic recovery after myocardial infarction.However, its introduction into the clinical mainstream is hampered by technical challenges with cell procurement, handling, selection, expansion, and application.In this issue of Circulation, Jujo et al 1 show that mobilization of endogenous cells by a clinically approved drug inhibiting the CXC-chemokine receptor 4 (CXCR4) improves myocardial recovery after infarction in a mouse model of ischemia/ reperfusion.
MEDICINE AND THE STATE.
Authors: C. H. PRESTON
Journal: JAMA (1898)

retention of feces and the multitudinous consequent ills have demanded our patient inquisitive considera- tion; and this study forces the conclusion, I believe, that the individual's escape is ultimately assured by process of development, but that for the normally formed infant, the physician will find the solution of the problem of difficult defecation in the solution of the stool.1077 Prospect Street.
Diagnosis by Radiocolloid Imaging of Postpartum Hepatic Necrosis in the Syndrome of Hemolysis, Elevated Liver Enzymes, and Low Platelets
Authors: ROBERT M. DAVIDSON, BRUCE J. BARRON, PHILLIP A. WHITE, ARMANDO E. FRAIRE
Journal: Clinical Nuclear Medicine (1992)

Postpartum hepatic necrosis in a patient with the syndrome of hamolysis, elevated liver enzymes, and low platelet count was diagnosed by Tc-99m SC liver-spleen imaging. Subsequent CT and ultrasonographic studies confirmed the nuclear medicine findings and suggested partial hepatic regeneration. Despite aggressive nonsurgical supportive care, the patient died. An autopsy confirmed focal massive hepatic necrosis.
The Use of Prisoners for Medical Research
Authors: Robert E. Hodges
Journal: JAMA (1967)

The moral and ethical implications and the practical operating code we have developed in Iowa were described by one of us in a University of London lecture on July 14, 1967. The basic principles do not differ from those set forth in an address to the Central Society for Clinical Research in Chicago in 1951.<sup>1</sup>Since this aspect of our interest has been dealt with elsewhere, we will confine our comments to the practical aspects of using prisoners from custodial institutions in Iowa in our clinical research. In the last analysis, the introduction of any new form of diagnosis or treatment, any new drug or medicine, is an experiment. There must be a first. Our problem, therefore, is to determine to what degree experimentation on human subjects is permissible and what should be the strict lines of control and consent. In recent months and years, books have been written,
Concentration of NADH-cytochrome b5 reductase in erythrocytes of normal and methemoglobinemic individuals measured with a quantitative radioimmunoblotting assay.
Authors: N Borgese, G Pietrini, S Gaetani
Journal: Journal of Clinical Investigation (1987)

The activity of NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is generally reduced in red cells of patients with recessive hereditary methemoglobinemia. To determine whether this lower activity is due to reduced concentration of an enzyme with normal catalytic properties or to reduced activity of an enzyme present at normal concentration, we measured erythrocyte reductase concentrations with a quantitative radioimmunoblotting method, using affinity-purified polyclonal antibodies against rat liver microsomal reductase as probe. In five patients with the "mild" form of recessive hereditary methemoglobinemia, in which the activity of erythrocyte reductase was 4-13% of controls, concentrations of the enzyme, measured as antigen, were also reduced to 7-20% of the control values. The concentration of membrane-bound reductase antigen, measured in the ghost fraction, was similarly reduced. Thus, in these patients, the reductase deficit is caused mainly by a reduction in NADH-cytochrome b5 reductase concentration, although altered catalytic properties of the enzyme may also contribute to the reduced enzyme activity.
HEREDITY AS A CAUSATIVE FACTOR OF INEBRIETY.
Authors: F. C. MYERS
Journal: JAMA (1898)

That heredity is a common cause of alcoholism, and that alcoholism is a disease, is becoming apparent to many medical men of the present day. In that good old book, the Bible, we are told that "The sins of the parents are visited upon the children to the third and fourth generations." That has been proven to be a fact, in the evil effects produced upon the system by the use of alcohol; the person whose brain and nervous system have been injured, and whose moral and will powers have been weakened, and whose stomach, liver, and other organs have become deranged by the use of alcohol, will transmit some of these derangements to his offspring. The modern study of the therapeutics of alcohol has proven, without a doubt, that it is not a stimulant or tonic, but an anesthetic and a narcotic, and that it should be classed, in
LARGE CARCINOMATOUS TUMOR OF THE LIVER.REMOVAL SEVENTEEN MONTHS AFTER NEPHRECTOMY FOR CARCINOMA OF THE LEFT KIDNEY. TEMPORARY RECOVERY.
Authors: THOMAS S. CULLEN
Journal: JAMA (1905)

Although Brunn in 1870 removed a small hepatic tumor, the surgery of the liver does not seem to have attracted much attention until Lin, in 1886, successfully performed a partial resection. Since that date, however, more than 100 resections of portions of the liver have been reported. Among the exhaustive treatises on the subject those of Terrier and Auvray,<sup>1</sup>in France, and of Langenbuch,<sup>2</sup>in Germany, deserve especial mention. In America the name of W. W. Keen<sup>3</sup>of Philadelphia is intimately associated with the development of the technic of liver surgery. He has not only reported three cases of resection, in all of which recovered took place, but has also published an exhaustive review of the previous literature. Nor should it be forgotten that a Baltimore surgeon, Dr. Louis McLane Tiffany,<sup>4</sup>was one of the first Americans successfully to remove a tumor of the liver. <i>The Nature of Hepatic Tumors.</i>
Proteomic analysis reveals that apolipoprotein A1 levels are decreased in patients with Budd–Chiari syndrome
Authors: Simone Talens, Jildou Hoekstra, Steffen P.G. Dirkx, Sarwa Darwish Murad, Jonel Trebicka, Elwyn Elias, Massimo Primignani, Juan-Carlos García-Pagán, Dominique C. Valla, Harry L.A. Janssen, Frank W.G. Leebeek, Dingeman C. Rijken
Journal: Journal of Hepatology (2010)
Cutaneous malignant melanoma. Publicity, screening clinics and survival-the Edinburgh experience 1982-90
Authors: R.M. HERD, E.J. COOPER, J.A.A. HUNTER, K. MCLAREN, U. CHETTY, A.C.H. WATSON, J. GOLLOCK
Journal: British Journal of Dermatology (2006)

The incidence of cutaneous malignant melanoma has increased considerably in south‐east Scotland over recent years. In 1987 the Cancer Research Campaign launched a project to aid the early detection, diagnosis and treatment of malignant melanoma. Edinburgh, chosen as one of seven centres in the U.K. to participate in the study, was provided with funding for a direct access pigmented lesion clinic from 1987 to 1989. The changes in the pattern of cutaneous malignant melanoma before, during and after the publicity campaign have been examined; between 1982 and 1990. The incidence of malignant melanoma doubled from 5.7 to 11.4/100,000 per annum. The percentage of thin tumours (Breslow thickness ≤ 1.5 mm) increased steadily and significantly (from 43% in 1982 to 68% in 1990), but the number of thick tumours (Breslow thickness > 3.0 mm) remained constant over the same period (22 ±3.8), The influence of Publicity was assessed using a questionnaire. Those who were influenced by publicity were stgnificantly younger and had more thin tumours (Breslow ≤ 1.5 mm) than those who were uninfluenced by publicity. Five‐year survival has significantly increased from 70% in the 1982–84 cohort to 84% in the 1987–89 cohort. The effect of the publicity campaign has been beneficial, but the impact on mortality cannot yet be assessed.
Photoageing shows histological features of chronic skin inflammation without clinical and molecular abnormalities
Authors: S. Bosset, M. Bonnet-Duquennoy, P. Barre, A. Chalon, R. Kurfurst, F. Bonte, S. Schnebert, B. Le Varlet, J.F. Nicolas
Journal: British Journal of Dermatology (2003)

Background Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis. Mast cells and macrophages, which are found in higher numbers in photoaged skin, have been implicated in this process. Objectives To analyse the phenotype of haematopoietic‐derived infiltrating cells in photodamaged skin. Methods Chronically sun‐exposed (preauricular) and control sun‐protected (postauricular) skin was recovered from eight healthy subjects undergoing cosmetic surgery (facial lifting). Results Histological analysis showed that sun‐exposed skin harboured more infiltrating mononuclear cells than sun‐protected skin. Cellular infiltrates were found at the periphery of areas of elastolysis around hair follicles in sun‐exposed sites, whereas they were found in the interfollicular dermis around blood vessels and around hair follicles in sun‐protected samples. Immunohistochemical analysis revealed an increased number of mast cells, macrophages and CD4+ CD45RO+ T cells in sun‐exposed dermis as well as a higher number of CD1a+ dendritic cells in sun‐exposed epidermis, compared with the sun‐protected samples. Thus photoageing displays histological features of chronic skin inflammation. However, no molecular sign of inflammation was observed and we even found a decreased expression of interleukin‐1β mRNA in sun‐exposed compared with sun‐protected sites. Furthermore, the patients' skin looked normal and did not display any clinical inflammation. Conclusions Collectively, these data show that chronic ultraviolet irradiation induces alterations of innate immune cells which are recruited in sun‐exposed skin without being activated.
Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats.
Authors: N Peng, S Oparil, Q C Meng, J M Wyss
Journal: Journal of Clinical Investigation (1996)

In spontaneously hypertensive rats (SHR), high NaCl diets increase arterial pressure and sympathetic nervous system activity by decreasing noradrenaline release in the anterior hypothalamic area (AHA), thereby reducing the activation of sympathoinhibitory neurons in AHA. Atrial natriuretic peptide (ANP) can inhibit the release of noradrenaline, and ANP concentration is elevated in the AHA of SHR. The present study tests the hypothesis that in SHR, local ANP inhibits noradrenaline release from nerve terminals in AHA. Male SHR fed a basal or high NaCl diet for 2 wk and normotensive Wistar Kyoto rats (WKY) fed a basal NaCl diet were studied. In SHR on the basal diet, microperfusion of exogenous ANP into the AHA elicited a dose-related decrease in the concentration of the major noradrenaline metabolite 3-methoxy-4-hydroxy-phenylglycol (MOPEG) in the AHA; this effect was attenuated in the other two groups. In a subsequent study, the ANP-C (clearance) receptor agonist c-ANP was microperfused into the AHA to increase extracellular concentration of endogenous ANP in AHA. c-ANP reduced AHA MOPEG concentration in SHR on the basal NaCl diet but not in the other two groups. These data support the hypothesis that local ANP inhibits noradrenaline release in the AHA and thereby contributes to NaCl-sensitive hypertension in SHR.
Statin Use and Risk of Colorectal Cancer
Authors: Patricia F. Coogan, Jacquelyn Smith, Lynn Rosenberg
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundStatins have anticancer activity in various cell types, including colon cancer cells. Although epidemiologic data on the relationship between statin use and the risk of colorectal cancer are limited, one case– control study reported a 50% reduction in colorectal cancer risk among statin users. We conducted a population-based case–control study to assess this association with respect to statin type, dose, and duration of use.
ACUTE POISONING WITH SODIUM FLUOROACETATE (COMPOUND 1080)
Authors: Joseph W. E. Harrisson
Journal: JAMA (1952)

Since the report of Kalmbach1on the rodenticide activity of fluoroacetate (compound 1080) this compound has been extensively used by government agencies, the armed forces, and privately employed exterminators. In spite of its high toxicity to all species, relatively few cases of human poisonings have been reported so far, none of which have ended fatally.2All of the victims took small, but unidentified, quantities of fluoroacetate. The toxic dose for human beings has not been established, but on the basis of animal studies it has been theorized as being approximately 5 mg. per kilogram of body weight. The case reported here ended fatally, pathological examination was performed, and the quantities of fluoroacetate in the organs were determined. For the experimental literature on fluoroacetate we may refer the reader to the recent reviews by Chenoweth3and by us.4  REPORT OF CASE  A white man, about 40 years
Where is the evidence for the existence of the Cancer Drugs Fund?
Authors: C. Chamberlain, W. Hollingworth
Journal: BMJ (2014)

Professor Peter Clark congratulates the Cancer Drugs Fund (CDF) for reimbursing drugs only at the lowest price proposed for use in the NHS, but he is later quoted conceding that “some [pharmaceutical] companies have seen the CDF as an easy route to funding . . . because they don’t have to drop the price to get CDF …
Adolescent development
Authors: Russell Viner
Journal: BMJ (2005)

Editor—Quinton acknowledges that apparent pubertal delay is a normal variant in most boys seen by general practitioners or by paediatric endocrinologists. However, he says that our advice, that boys aged 15 or over with a testicular volume of 4 ml or more can be reassured that puberty is beginning, is potentially misleading, as 4 ml testes are within the range found in adult men with the uncommon condition of irreversible hypogonadotrophic hypogonadism.

Our advice is appropriate for boys who present to general practitioners. The absence of any signs of puberty, or lack of further progression through puberty over the next six months should, of course, be viewed with suspicion and merit referral to a paediatric endocrinology service for full investigation, including consideration of conditions such as hypogonadotrophic hypogonadism.

Quinton thinks that even the normal variant of constitutional delay in growth and puberty can have adverse psychosocial consequences.1 However, newer larger studies have shown that boys who are small or whose adolescence is delayed are not psychologically disadvantaged.2 Rather than overtreating numbers of normal boys, we focus on improving the communication skills of general practitioners in discussing issues such as pubertal timing with young people.
Cold atmospheric plasma in combination with mechanical treatment improves osteoblast growth on biofilm covered titanium discs
Authors: Kathrin Duske, Lukasz Jablonowski, Ina Koban, Rutger Matthes, Birte Holtfreter, Axel Sckell, J. Barbara Nebe, Thomas von Woedtke, Klaus Dieter Weltmann, Thomas Kocher
Journal: Biomaterials (2015)
Flow Cytometric Evaluation Of Minimal Residual Disease In Adult Acute Lymphoblastic Leukemia Using a Simplified, Single-Tube Approach
Authors: Roger Belizaire, Olga Pozdnyakova, Daniel J. DeAngelo, Betty Li, Karry Charest, Richard M. Stone, Martha Wadleigh, David P. Steensma, Gabriela Motyckova, David M. Dorfman
Journal: Blood (2013)
Effects of stopping smoking for 48 hours on oxygen availability from the blood: a study on pregnant women.
Authors: J M Davies, I P Latto, J G Jones, A Veale, C A Wardrop
Journal: BMJ (1979)

The effects of stopping smoking for 48 hours on factors governing the availability of oxygen from the blood--that is, carboxyhaemoglobin (COHb), haemoglobin-oxygen (HbO2) affinity, and haemoglobin concentration--were measured in women in the last trimester of pregnancy. Three groups were studied: smokers, smokers who stopped smoking for 48 hours, and non-smokers. The 22 smokers had higher initial COHb values and greater HbO2 affinity than the 10 non-smokers, but their total haemoglobin concentrations were also higher, so that their oxygen availability was not significantly reduced. In the 11 smokers who stopped the reduction in COHb and decrease in HbO2 affinity led to a significant increase of 8% in "available oxygen" in 48 hours. Since even small improvements in oxygen delivery to the tissues may confer critical benefit to the fetus, particularly during labour or when exposed to general anaesthesia, smoking should be discouraged for 48 hours before elective deliveries. The same consideration might reasonably be applied to patients undergoing general anaesthesia for all elective operations.
Bradykinin Antagonism Inhibits the Antigrowth Effect of Converting Enzyme Inhibition in the Dog Myocardium After Discrete Transmural Myocardial Necrosis
Authors: Kenneth M. McDonald, James Mock, Antonio D’Aloia, Todd Parrish, Kate Hauer, Gary Francis, Arthur Stillman, Jay N. Cohn
Journal: Circulation (1995)

Background Converting enzyme inhibitor (CEI) therapy, but not angiotensin II subtype I receptor blockade, has been shown to attenuate left ventricular remodeling in the dog after transmyocardial direct current (DC) shock. The purpose of this study was to address the importance of preservation of bradykinin to the antiremodeling effect of CEI treatment in this model. Methods and Results Twenty-four hours after DC shock, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated with ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist. To assess change in left and right ventricular structure, a magnetic resonance imaging (MRI) study was performed 4 weeks after DC shock and compared with a baseline MRI study performed before DC shock. The increase in left ventricular mass (mean±SEM) in the control group was similar to that observed in the CEI–HOE 140 group (+0.73±0.19 versus +0.75±0.18 g/kg, P =NS), but both were greater than the change in mass in the ramipril group (−0.48±0.13 g/kg, P =.004 and P =.0005, respectively). No significant change occurred in left ventricular volume or right ventricular structure in any group. Mean arterial pressure was reduced by ramipril compared with the control group (−8±2 versus +7±2 mm Hg, P =.03), and this effect was not blunted by the addition of HOE 140 (−7±3 mm Hg). Conclusions Prevention by ramipril of the early increase in left ventricular mass in the DC shock model appears to be related to the preservation of bradykinin.
Diet and the Prevention of Osteoporotic Fractures
Authors: Richard L. Prince
Journal: New England Journal of Medicine (1997)

One of the striking demographic features of all countries in the late 20th century is the increasing longevity of both men and women. Unfortunately, this extension of life expectancy has not been associated with a similar increase in disability-free years of life, so that many old people have increasing pain and dysfunction during their last years. Osteoporotic fractures are an important contributor to these problems, because they affect 50 percent of women and 30 percent of men over the age of 50 years.1 What can be done to prevent osteoporotic fractures? The answer to this question goes to the fundamentals . . .