tbuckley/cabot-search huggingface dataset:
Abstract 18: Targeted epidermal ablation of EGFR causes local and systemic inflammation
Authors: Francesca Mascia, Gary Lam, David Threadgill, Stuart H. Yuspa
Journal: Cancer Research (2010)

Abstract EGFR is overexpressed or mutated in a variety of malignancies, and it plays a fundamental role in tumor development and progression, in the angiogenetic process and in the metastatic spread of tumors. As a result investigators have developed approaches to inhibit EGFR activation, with the aim of blocking tumor growth and invasion. The most common adverse effect seen with EGFR inhibition therapy is a pronounced skin inflammatory response (papulopustular rash) that can affect different areas of the body with variable severity. Interestingly, in vitro and in vivo experiments demonstrate that the pharmacological blockade of EGFR or ERK1/2, induces chemokine expression in epidermal keratinocytes and in turn leads to worsening of skin inflammatory conditions. Recent findings suggest a link between chemokine expression and EGFR status in the skin lesions of patients undergoing EGFR therapy and during tumor progression in BCC (basal cell carcinoma) and SCC (squamous cell carcinoma) skin lesions. Given these previous findings we believe that the study of the regulatory functions of the EGFR-ERK1/2 pathway on skin inflammatory mediators will help in understanding not only the adverse effect of this broad class of antitumor drugs but will possibly help to understand if and how they can modify the tumor microenvironment. In this study a mouse model was developed to better characterize the role of EGFR in the control of skin inflammation. By crossing Keratin 5 driven Cre recombinase transgenics with EGFR floxed mice, EGFR was ablated in the epidermis. During the first week of life, double transgenics started to display a strong skin phenotype with aberrant hair growth. During the following weeks the skin of these mice became progressively more inflamed with abundant neutrophilic infiltrate, scaly, dry and less elastic and underwent cycles of hair growth and hair loss. Double transgenic mice experienced a strong pruritus through their entire life, and their scratching behavior caused skin erosions. Tissue samples isolated from skin of adult double transgenics contained high levels of CD45 antigen and increased mRNA levels of a subset of inflammatory mediators namely CCL17, CCL20, CCL2, TNF-α, IL-6, IL-17, IL-18, and G-CSF. Targeted knockout mice also displayed hematological abnormalities with a higher number of circulating CD11b/Gr1 positive cells, extramedullary hematopoiesis and higher plasma levels of G-CSF, IL-1ra, IL-17, IL-6 and CCL2. These data indicate that the local absence of EGFR triggers local and systemic inflammatory responses. Therefore, this model represents a valuable tool to further investigate the control of EGFR in the maintenance of a balanced immuno-homeostasis of the skin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 18.
Loss of Associated Movements of the Eyes under Chloroform and in Disease
Authors: F. Warner
Journal: BMJ (1877)

febrile conditions, but would submit that its real value lies in the influence it exerts over that section of the nervous system which con- trols the constructive and destructive forces which are constantly in operation in the living body; and that when, as in fever, assimilative nutrition or constructive force is in abeyance, cuca restrains tissue-metamorphosis or destructive force.P. S.-Perhaps, for the benefit df those who may wish to try the tincture of erythroxylon cuca, as I found great difficult in obtaining it, I may mention that I have lately obtained it in large quantities from Messrs.
The Burden of Responsibility
Authors: Robert A. Nover
Journal: JAMA (1967)

ABSTRACT To the Editor:— Dr. Solomon correctly emphasized the burden of responsibility of the physician in assessing the possible suicidal intent of his patients (199:321, 1967). In the case of the terminally ill patient, however, I take exception to his statement that the physician must guard the patient against himself. Too often in the case of the patient dying with cancer, the physician is apt to neglect the rights of the patient in the interest of serving the wishes of others and to assuage his own guilt.In certain cases, where the chances that death will come are certain, I feel that the patient should be allowed to decide for himself if he wishes further treatment to prolong his life. Some patients when faced with this choice prefer to die intact. In the last analysis, the dignity of dying belongs to the patient, and this right should not be abrogated
Apoptosis and Heart Failure
Authors: R S Williams
Journal: New England Journal of Medicine (1999)

Programmed cell death (apoptosis) was unknown to William Osler and Paul Dudley White, but physicians today must grapple with the uneasy knowledge that all of our cells actively maintain the machinery of self-destruction and must continuously hold it in check to avoid that fate.Apoptosis was first observed as a driving force that shapes the structure of tissues during embryonic development. A familiar example is the separation of the digits of our hands and feet from the blunt ends of the fetal limbs. Today, we also recognize apoptosis as a mechanism whereby damaged cells are removed from the body during . . .
Effects of milrinone on left ventricular remodeling after acute myocardial infarction.
Authors: P Jain, E J Brown, E G Langenback, E Raeder, O Lillis, J Halpern, J A Mannisi
Journal: Circulation (1991)

Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction.Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals.Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation.
A Grotesque Old Woman
Authors: C. Cook
Journal: BMJ (2009)

Hanging in the National Gallery, London, is A Grotesque Old Woman , by Quienen Massys, contrasting starkly with the images of youth and beauty that otherwise dominated the Renaissance.⇓ The painting always attracts attention and is one of the most popular in the gallery. A favourite of art historians and casual observers alike, this iconic image may even have inspired Leonardo da Vinci, although it is now widely accepted that Massys copied da Vinci. The old woman has spawned several impersonations, such as the illustrator John Tenniel’s …
Pitfalls in the diagnosis of subarachnoid haemorrhage
Authors: F. Coakley, N. Messios, B. Morgan, R. Owen
Journal: BMJ (1995)

Treating CS gas injuries to the eye Exposure at close range is particularly dangerous EDr1OR,-Jean-Paul Yih's editorial on injuries to the eye caused by O-chlorobenzylidene malono- nitrile (CS) gas, or tear gas, draws attention to the short term effects of the gas on the eye and suggests that such injuries may well be a future problem as individual police officers in Britain will soon be carrying pocket aerosols of CS gas.' Yih implies that the ocular toxicity of CS gas is rapidly reversible; however, the ocular irritation from 1-chloroacetophenone (another tear gas agent) typically lasts only 15 minutes but may persist for up to three days.2The problems are particularly pronounced when the charge of tear gas is fired at close range: powder infiltration of the conjunctiva, cornea, and sclera will occur.The forces are so great that conjunctival tearing may occur.Corneal stromal oedema and later deep vascularisation may ensue, and a multitude of complications have been reported, including symblepharon, pseudopterygium, infective keratitis, trophic ketatopathy, posterior synechia, secondary glaucoma, cataracts, hyphaema, vitreous haemor- rhage, and traumatic optic neuropathy.' Thus
LEAD EXTRACTION IN AFRICAN AMERICANS: NOT DIFFERENT FROM THE REST
Authors: Madhu Reddy, Kirill Lipatov, Gopi Ponnaganti, Arun Kanmanthareddy, Jayasree Pillarisetti, Rhean Linette Pimentel, Martin Emert, Raghuveer Dendi, Sudharani Bommana, Dhanunjaya Lakkireddy, Loren Berenbom
Journal: Journal of the American College of Cardiology (2014)
Acute Effects of β <sub>1</sub> -Selective and Nonselective β-Adrenergic Receptor Blockade on Cardiac Sympathetic Activity in Congestive Heart Failure
Authors: Gary E. Newton, John D. Parker
Journal: Circulation (1996)

Background β-Blockers may reduce cardiac sympathetic activity in patients with heart failure by antagonizing β-adrenergic receptors that facilitate sympathetic outflow to the heart. To explore this possible effect of β-blockade, we measured cardiac norepinephrine spillover responses in patients with heart failure after the acute administration of either propranolol, a nonselective β-blocker, or metoprolol, a β 1 -selective agent. Methods and Results Eighteen patients were studied. Repeated intravenous doses of propranolol (0.5 mg; nine patients; left ventricular ejection fraction, 14±2%) or metoprolol (1.0 mg; nine patients; left ventricular ejection fraction, 18±2%) were administered until one of the following end points was reached: a 15% decrease in heart rate, left ventricular +dP/dt, or mean arterial blood pressure or a 5 mm Hg increase in left ventricular end-diastolic pressure. Propranolol (mean dose, 2.0 mg) and metoprolol (mean dose, 3.6 mg) caused similar reductions in heart rate, +dP/dt, and coronary sinus plasma flow. Cardiac norepinephrine spillover was reduced after propranolol (277±55 to 262±53 pmol/min, P &lt;.05) but was increased after metoprolol (233±57 to 296±82 pmol/min, P &lt;.05). In a comparison of the two groups, the decrease in spillover after propranolol was significantly different than the increase seen after metoprolol ( P &lt;.01). Conclusions The administration of a β 1 -selective antagonist was associated with increased cardiac norepinephrine spillover. In contrast, the administration of a nonselective β-blocker until similar hemodynamic end points were reached caused a reduction in norepinephrine spillover. This suggests that in patients with heart failure, nonselective β-blockade may have favorable inhibitory effects on cardiac sympathetic activity.
The Site of Upper Gastrointestinal Bleeding
Authors: Irving M. Ariel
Journal: JAMA (1962)

The site of upper gastrointestinal bleeding, whether from the esophagus or stomach or duodenum, is determined by measuring radioactivity of the aspirate after intravenous injection of red blood cells tagged with radioactive chromium. A Necheles tube permits the sealing off of the esophageal aspirate from the gastric or duodenal aspirate. Of 15 patients tested, 6 were found to have hemorrhage from the stomach or duodenum, and 5 were bleeding from the esophagus. One patient with cirrhosis believed to be bleeding from esophageal varix was found to be bleeding from the duodenum (duodenal ulcer). The test was unsatisfactory in 4 patients because active bleeding had ceased.
Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib
Authors: Thomas M. Rnger, Silvano Adami, Claude-Laurent Benhamou, Edward Czerwiski, Jordi Farrerons, David L. Kendler, Linda Mindeholm, Giuseppe Realdi, Christian Roux, Vanessa Smith
Journal: Journal of the American Academy of Dermatology (2011)
Protein abnormalities in macrophages bearing asbestos.
Authors: P Lemkin, L Lipkin, C Merril, S Shifrin
Journal: Environmental Health Perspectives (1980)

Computerized techniques for the evaluation of O'Farrell two-dimensional electrophoretic gels have been applied to proteins derived from asbestos bearing macrophages. Preliminary results indicate definite changes in the protein content of cells depending on fiber phagocytosis.
Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma
Authors: Meng Li, Hong Zhao, Xiaosong Zhang, Laura D Wood, Robert A Anders, Michael A Choti, Timothy M Pawlik, Hubert D Daniel, Rajesh Kannangai, G Johan A Offerhaus, Victor E Velculescu, Linfang Wang, Shibin Zhou, Bert Vogelstein, Ralph H Hruban, Nick Papadopoulos, Jianqiang Cai, Michael S Torbenson, Kenneth W Kinzler
Journal: Nature Genetics (2011)
STUDIES ON THE SUPRARENAL CORTEX
Authors: George A. Harrop, Albert Weinstein, Louis J. Soffer, John H. Trescher
Journal: The Journal of Experimental Medicine (1933)

1. The basal oxygen consumption, respiratory quotient, blood flow, blood pressure, and the changes in concentration of the arterial blood were determined in suprarenalectomized dogs (a) when receiving injections of cortical extract (Swingle-Pfiffner), (b) during suprarenal insufficiency induced by withdrawal of the injections, and (c) during the period of recovery brought about by resumption of extract injections. 2. Reasons are advanced for the view that the hemoconcentration which occurs is probably due to loss of fluid through the kidneys, rather than by increased capillary permeability and loss into the tissues, or by loss through the gastrointestinal tract. 3. The loss of fluid from the plasma and tissues will explain the symptoms which follow withdrawal of injections of the hormone, as well as the fatal outcome. The assumption that the suprarenal cortex or its hormone has a detoxifying action upon some product of metabolism is thus rendered unnecessary.
Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss
Authors: Heng Xu, Giles W Robinson, Jie Huang, Joshua Yew-Suang Lim, Hui Zhang, Johnnie K Bass, Alberto Broniscer, Murali Chintagumpala, Ute Bartels, Sri Gururangan, Tim Hassall, Michael Fisher, Richard Cohn, Tetsuji Yamashita, Tal Teitz, Jian Zuo, Arzu Onar-Thomas, Amar Gajjar, Clinton F Stewart, Jun J Yang
Journal: Nature Genetics (2015)
Perception-action as reciprocal, continuous, and prospective
Authors: Jeffrey B. Wagman
Journal: Behavioral and Brain Sciences (2008)

Abstract From the perspective of ecological psychology, perception and action are not separate, linear, and mechanistic processes that refer to the immediate present. Rather, they are reciprocal and continuous and refer to the impending future. Therefore, from the perspective of ecological psychology, delays in perception and action are impossible, and delay compensation mechanisms are unnecessary.
Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation
Authors: Shankar S. Iyer, Qiong He, John R. Janczy, Eric I. Elliott, Zhenyu Zhong, Alicia K. Olivier, Jeffrey J. Sadler, Vickie Knepper-Adrian, Renzhi Han, Liang Qiao, Stephanie C. Eisenbarth, William M. Nauseef, Suzanne L. Cassel, Fayyaz S. Sutterwala
Journal: Immunity (2013)
Italian hospitals must reduce duplication of surgical units to improve results
Authors: M. Day
Journal: BMJ (2008)

Italy must encourage greater specialisation in its hospitals’ surgical units, along the lines of US and UK institutions, to cut death rates, the country’s surgeons were told last week.

Carlo Staudacher, an surgeon at the Istituto Scientifico Ospedale San Raffaele in Milan, told the national congress of the Italian Society of Surgery that in hospitals throughout the country surgical teams were carrying out major procedures that they were not best qualified to do.

The problem, he said, was that many hospitals had three or four surgical units performing the same procedures, often with radically different success rates. …
Thalassaemia, Glucose-6-Phosphate Dehydrogenase Deficiency, Sickling, and Malarial Endemicity in Greece: A Study of Five Areas
Authors: G. Stamatoyannopoulos, Ph. Fessas
Journal: BMJ (1964)

This study was carried out in 1961 and 1962.A total of 2,143 subjects were studied for thalassaemia trait; of these, 1,474 were also examined for G.-6-P.D.d. and 1,021 for Hb S. Five areas were screened: Karditsa, Elasson, Corfu, Petro- magoula, and Serifos (see Map).The characterization of the malarial endemicity in each area before 1945 was based on older data (Livadas and Sphangos, 1940) and on information obtained through the local public health centres.
What If Americans Ate Less Fat?
Authors: Warren S. Browner
Journal: JAMA (1991)

Americans consume an average of 37% of their energy intake as fat. Many authorities recommend restricting fat intake to 30% of energy intake to reduce the rates of coronary heart disease and perhaps of cancers of the breast, colon, and prostate. Based on the assumptions that underlie those recommendations, we estimated the effect of this dietary change on mortality. If all Americans restricted their intake of dietary fat by reducing consumption of saturated fat and accompanying dietary cholesterol, the corresponding reductions in serum cholesterol levels could reduce coronary heart disease mortality rates by 5% to 20%, depending on age. If the relationship between dietary fat and cancer is as strong as has been observed in some studies, the proportional effects on mortality from fat-related cancers could be even greater, although the absolute effects--given the lower mortality rates--would be smaller. Overall, if the assumptions are correct, about 42,000 of the 2.3 million deaths that would have occurred in adults each year in the United States could be deferred. This 2% benefit, equivalent to an increase in average life expectancy of 3 to 4 months, would accrue chiefly to people over the age of 65 years. If recent concerns about the possibly harmful effects of cholesterol lowering on mortality from noncardiovascular causes--which mainly affect younger persons--are valid, these relatively modest benefits would be overestimates of the actual effect.
Urinary Incontinence among Male Veterans Receiving Care in Primary Care Clinics
Authors: Steven H. Smoger, Toni L. Felice, Goetz H. Kloecker
Journal: Annals of Internal Medicine (2000)

Background: Male urinary incontinence is not a well-investigated subject. Objective: To determine the prevalence and consequences of incontinence in men. Design: Cross-sectional survey. Setting: 3 primary care clinics in a Kentucky Veterans Affairs facility. Patients: 840 men with a mean age of 59.8 years (range, 25 to 93 years). Measurements: Written survey on patient demographic information and continence, including the Incontinence Impact Questionnaire. Results: Among all study patients, 32.3% reported incontinence within the past 12 months and 13.8% (43% of those who were incontinent) reported at least weekly episodes. Age did not correlate with frequency or amount of urine loss. Frequency correlated with emotional health, social relationships, physical activity, and travel. Greater amounts of lost urine had a stronger effect on emotional health, social relationships, and travel. Among men with incontinence, only 32% had discussed incontinence with their medical provider but 75% desired evaluation and treatment. Conclusions: Urinary incontinence is common among male veterans and affects all age groups. Although incontinence often has unfavorable consequences on quality of life and although men with incontinence desired treatment, they seldom discussed the problem with medical providers. Systematic screening of men for urinary incontinence may be necessary.
Role of protein kinase C in parathyroid hormone stimulation of renal 1,25-dihydroxyvitamin D3 secretion.
Authors: M Janulis, V Tembe, M J Favus
Journal: Journal of Clinical Investigation (1992)

PTH is a major regulator of renal proximal tubule 1,25(OH)2D3 biosynthesis. However, the intracellular pathways involved in PTH activation of the mitochondrial 25-hydroxyvitamin D3-1 alpha-hydroxylase (1-OHase) remain unknown. PTH can activate both the adenylate cyclase/protein kinase A (PKA) and the plasma membrane phospholipase C/protein kinase C (PKC) pathways. The present study was undertaken to determine whether PKC may mediate PTH activation of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity. Rat PTH 1-34 fragment in vitro translocated PKC activity from cytosolic to soluble membrane fraction from freshly prepared rat proximal tubules. Physiologic concentrations (10(-11)-10(-10) M) of rat PTH 1-34 fragment increased PKC translocation three- to fourfold while PKA activity ratio increased at PTH 10(-7) M. PTH stimulation of PKC and PKA was reduced in the presence of staurosporine (10 nM) by 41 and 29%, respectively. Sangivamycin (10 and 50 microM) also reduced PTH-stimulated PKC translocation, but did not alter PKA activity ratio. In vitro perifusion of renal proximal tubules with PTH (10(-11) M) increased 1,25(OH)2D3 steady-state secretion two- to fourfold. Sangivamycin at the same concentration that inhibited PKC translocation by 52% completely inhibited PTH-stimulated 1,25(OH)2D3 secretion. The present studies indicate that the phospholipase C/PKC pathway may mediate PTH stimulation of mammalian renal proximal tubule 1,25(OH)2D3 secretion.