tbuckley/cabot-search huggingface dataset:
Mutations in DEPDC5 cause familial focal epilepsy with variable foci
Authors: Leanne M Dibbens, Boukje de Vries, Simona Donatello, Sarah E Heron, Bree L Hodgson, Satyan Chintawar, Douglas E Crompton, James N Hughes, Susannah T Bellows, Karl Martin Klein, Petra M C Callenbach, Mark A Corbett, Alison E Gardner, Sara Kivity, Xenia Iona, Brigid M Regan, Claudia M Weller, Denis Crimmins, Terence J O'Brien, Rosa Guerrero-López, John C Mulley, Francois Dubeau, Laura Licchetta, Francesca Bisulli, Patrick Cossette, Paul Q Thomas, Jozef Gecz, Jose Serratosa, Oebele F Brouwer, Frederick Andermann, Eva Andermann, Arn M J M van den Maagdenberg, Massimo Pandolfo, Samuel F Berkovic, Ingrid E Scheffer
Journal: Nature Genetics (2013)
On the Ledge: A Doctor's Stories From the Inner City
Authors: Bernadine Z. Paulshock
Journal: JAMA (1997)

All doctors are trained to tell stories: "This 45-year-old man was awakened from sleep by..." While it is possible that such a routine case presentation might include the fact that the patient is a truck driver or a former drug addict, such details are not considered as important by most presenters as the details of the patient's symptoms. Only after their training are doctors apt to learn differently, sometimes to their great surprise, the importance of their patients' lifestyles and environments to the care of their medical problems. In<i>On the Ledge</i>, Neil Skolnik writes of his 2 years at a family medicine clinic serving Philadelphia's inner-city poor. He admits that his writing is a "purging of frustration." These fine and interesting accounts of the patients he saw arose from his dismay at the living conditions of the inner-city poor for whom he had medical responsibility. He seems surprised at
Diabetic Retinopathy
Authors: Franklin H. Epstein, Thomas J. Merimee
Journal: New England Journal of Medicine (1990)

IT is estimated that 5000 patients with diabetes in the United States and 30,000 to 40,000 worldwide become blind each year from retinopathy. Despite advances in the use of photocoagulation and vitrectomy, diabetic retinopathy has been the leading cause of blindness in Great Britain, North America, Europe, and Scandinavia since 1974.1 The sequence of anatomical changes in the retina leading to blindness in diabetes is fairly well defined,2 3 4 but the causes are poorly understood. Most components of diabetic retinopathy, including endothelial proliferation, capillary closure, and preretinal neovascularization, occur in other diseases. However, the constellation of lesions, from early thickening of . . .
BBC3 (PUMA) regulates developmental apoptosis but not axonal injury induced death in the retina
Authors: Jeffrey M Harder, Richard T Libby
Journal: Molecular Neurodegeneration (2011)

Naturally occurring apoptosis is a developmental process that shapes the retina by eliminating overproduced neurons. In the absence of the proapoptotic Bcl-2 family member BAX, developmental apoptosis in the retina is disrupted and extra neurons survive. It is unknown how BAX is activated or if this regulation varies between neuronal types and subtypes. Since the Bcl-2 family members BIM, BID, and BBC3 (PUMA) are powerful direct activators of BAX, we used mice deficient for each of these genes to investigate their importance in developmental apoptosis.Bax deficient mice have an increase in retinal ganglion cells (RGCs), bipolar cells and dopaminergic amacrine cells, but not photoreceptors, horizontal cells or cholinergic amacrine cells. The retinas of adult Bim and Bid deficient mice appeared to have no increase in any retinal cell type. Bbc3 deficient mice, either homozygous or heterozygous for a null allele of Bbc3, had an increase in the same cell types as Bax deficient mice. An analogous result may occur in the brain where, similar to Bax deficient mice, Bbc3 deficient mice have a larger gross brain weight compared to wild type mice. In contrast to its developmental role, BBC3 did not appear to be a primary factor in BAX-dependent axonal injury induced neurodegeneration in adult RGCs.The regulation of BAX activation in the retina appears to be complex, dependent on the developmental stage of the animal, the nature of the insult and even the type of neuron.
Risk stratification of emergency department patients with acute coronary syndromes using P-Selectin
Authors: Judd E Hollander, M.Ranu Muttreja, Margaret R Dalesandro, Frances S Shofer
Journal: Journal of the American College of Cardiology (1999)

OBJECTIVES We compared the predictive properties of P-selectin to creatine kinase, MB fraction (CK-MB) for detecting acute myocardial infarction (AMI), acute coronary syndromes (ACS) and serious cardiac events upon emergency department (ED) arrival. BACKGROUND Practioners detecting early diagnosis of ACS have focused on cardiac markers of myocardial injury. Plaque rupture/platelet aggregation precedes myocardial ischemia. Therefore, markers of platelet aggregation may detect ACS earlier than cardiac markers. METHODS Consecutive patients with potential ACS presenting to an urban university ED were identified by research assistants who screened all ED patients between November 12, 1997 and January 31, 1998. Whole blood was drawn at presentation and 1 h later and rapidly stained and fixed for membrane P-selectin assay and plasma was separated for soluble P-selectin assay. Creatine kinase, MB fraction values were determined using standard immunoassay techniques. Clinical history and hospital course were followed daily. Outcomes were AMI, ACS (AMI and unstable angina) and serious cardiac events. Receiver operator characteristic curves were derived for CK-MB, and soluble and membrane-bound P-selectin to determine the optimal cutoff values. Predictive properties were calculated with 95% confidence intervals. RESULTS A total of 263 patients were enrolled. They had a mean age of 56.5 ± 14 years; 52% were male. There were 22 patients with AMI; 87 patients with ACS and 54 patients with serious cardiac events. Creatine kinase, MB fraction had a higher specificity for detection of AMI, ACS and serious cardiac events than both soluble and membrane-bound P-selectin. At the time of ED presentation, the specificity of CK-MB, and soluble and membrane-bound P-selectin for AMI was 91% versus 76% versus 71%; for ACS, 95% versus 79% versus 71%, and for serious cardiac events, 91% versus 76% versus 72% (p < 0.05). The sensitivities for AMI were 50% versus 45% versus 32%; for ACS, 26% versus 35% versus 30%, and for serious cardiac events, 29% versus 35% versus 36%. CONCLUSIONS Although theoretically attractive, the use of soluble and membrane-bound P-selectin for risk stratification of chest pain patients at the time of ED presentation does not appear to have any advantages over the use of CK-MB.
Air pollution and child mortality: a time-series study in São Paulo, Brazil.
Authors: G M Conceição, S G Miraglia, H S Kishi, P H Saldiva, J M Singer
Journal: Environmental Health Perspectives (2001)

Although most available evidence relating air pollution and mortality was obtained for adults, pollution has been also associated with increased mortality in children, but in a significantly smaller number of studies. This study was designed to evaluate the association between child mortality and air pollution in the city of São Paulo, Brazil, from 1994 to 1997. Daily records of mortality due to respiratory diseases for children under 5 years of age were obtained from the municipal mortality information improvement program. Daily concentrations of sulfur dioxide (SO(2)), carbon monoxide (CO), inhalable particulate matter less than 10 microm in diameter (PM(10)), and ozone were obtained from the state air pollution controlling agency. Information on minimum daily temperature and on relative humidity were obtained from the Institute of Astronomy and Geophysics of the University of São Paulo. Statistical analysis was performed through generalized additive models considering a Poisson response distribution and a log link. Explanatory variables were time, temperature, humidity, and pollutant concentrations. The loess smoother was applied to time (in order to model seasonality) and temperature. Significant associations between mortality and concentrations of CO, SO(2), and PM(10) were detected. The coefficients (and standard errors) of these three pollutants were 0.0306 (0.0076), 0.0055 (0.0016), and 0.0014 (0.0006), respectively. The observed associations were dose dependent and quite evident after a short period of exposure (2 days). According to the proposed model and considering the mean of the pollutant concentration during the period of the study, the estimated proportions of respiratory deaths attributed to CO, SO(2), and PM(10), when considered individually, are around 15, 13, and 7%, respectively.
Physician Poll on Cancer Prevention
Authors: Robert J. Samp
Journal: JAMA (1962)

Over 1,400 physicians, mostly practicing doctors in Wisconsin, have been asked their opinions about 40 possible measures to prevent cancer. The resultant list of cancer preventatives, in order of the highest acceptance, is presented here. The majority of the doctors agreed on the first 10 and the last 10 measures. Clinical preventive measures, such as surgery on polyps, nodules, and premalignant lesions, received the highest acceptance. Laboratory or experimental discoveries relative to carcinogenesis were rated lower. The latter group includes studies on air pollution, food additives, industrial carcinogens, and tobacco. Certain other measures, such as circumcision, protection from sunlight, and avoiding or treating vigorously any avitaminoses, were less acceptable. The poll indicates the belief that some cancer is preventible, but there is much to be done in educating the professions on presently available means, as well as in exploring the many other possibilities.
Effects of Protriptyline on Diurnal and Nocturnal Oxygenation in Patients with Chronic Obstructive Pulmonary Disease
Authors: Frédéric Sériès
Journal: Annals of Internal Medicine (1990)

To determine the effects of a nonsedating tricyclic antidepressant (protriptyline) on pulmonary function (lung volume, expiratory flow), arterial blood gases, sleep architecture, and sleep-induced breathing abnormalities in patients with chronic obstructive pulmonary disease.A before-and-after trial in which patients, blinded to treatment, were given a placebo for 2 weeks, followed by 2 and 10 weeks of protriptyline treatment.Referral-based pulmonology clinic in a public institution.Sixteen outpatients were enrolled in the trial. Complete results for 11 patients and partial results for 3 patients are presented.Patients were evaluated at baseline, after receiving placebo for 2 weeks, and after 2 and 10 weeks of protriptyline therapy (20 mg/d, taken at bedtime).At baseline, for the whole group, forced expiratory volume in 1 second (FEV1) was 1.0 +/- 0.08 L (mean +/- SE); the partial pressure of O2 in arterial blood (PaO2) was 59 +/- 1.2 mm Hg; and the partial pressure of CO2 in arterial blood (PaCO2) was 48.9 +/- 1.2 mm Hg. These variables remained stable after placebo. Pulmonary function test results were unchanged with protriptyline therapy. Arterial blood gas levels improved with such therapy: PaO2 levels increased by 5.1 +/- 1.4 mm Hg after 2 weeks and 6.7 +/- 2.4 mm Hg after 10 weeks (P less than 0.01); PaCO2 levels decreased by 4.2 +/- 0.9 mm Hg after 2 weeks and 2.2 +/- 1.1 mm Hg after 10 weeks (P less than 0.01). Total sleep times were similar at these visits. The only change in sleep architecture was a significant decrease in rapid eye movement (REM) sleep. The lowest value for the saturation of hemoglobin with O2 in arterial blood (SaO2) seen during sleep was 72.0% +/- 2.0% at baseline. After 2 and 10 weeks of protriptyline therapy, SaO2 values increased by 7.1% +/- 1.6% and 5.0% +/- 2.1%, respectively (P less than 0.01). With protriptyline therapy, the cumulative SaO2 curve, derived from data obtained during sleep, shifted down and to the right.Protriptyline improves diurnal and nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. These changes are not related to changes in pulmonary mechanics.
l-Triiodothyronine and l-Reverse-Triiodothyronine Generation in the Human Polymorphonuclear Leukocyte
Authors: Kenneth A. Woeber, Betty A. Maddux
Journal: Journal of Clinical Investigation (1978)

Extrathyroidal monodeiodination of l-thyroxine (T4) is the principal source of l-triiodothyronine (T3) and l-reverse-triiodothyronine (rT3) production. To define some of the cellular factors involved, we examined T3 and rT3 generation from added nonradioactive T4 in human polymorphonuclear leukocytes, using radioimmunoassays to quantify the T3 and rT3 generated. Under optimum incubation conditions which included a pH of 6.5 in sucrose-acetate buffer, the presence of dithiothreitol as a sulfhydryl-group protector, and incubation in an hypoxic atmosphere, significant net generation of T3 and rT3 was observed. Of the several subcellular fractions studied, the particulate fraction obtained by centrifugation at 27,000 g was found to possess the highest T3- and rT3-generating activities per unit quantity of protein. With respect to T3 generation from substrate T4, the Km was 5 μM and the Vmax was 7.2 pmol/min per mg protein. Propylthiouracil, methimazole, and prior induction of phagocytosis inhibited both T3 and rT3 generation, but T3 generation was inhibited to a greater extent. rT3, in a concentration equimolar to that of substrate T4, did not alter T3 generation, but inhibited T3 generation when the molar ratio of rT3 to T4 approached 10:1. Under the incubation conditions employed, particulate fractions of leukocytes obtained from five cord blood samples displayed an essentially normal relationship between T3- and rT3-generating activities, despite the distinctly divergent serum T3 and rT3 concentrations in these samples. From our findings, we draw the following conclusions: (a) the human polymorphonuclear leukocyte possesses the ability to generate T3 and rT3 from substrate T4; (b) the T3- and rT3-generating activities are associated principally with the 27,000 g particulate fraction and display enzymic characteristics with a sulfhydryl-group requirement; (c) T3-generating activity appears to be more susceptible to inhibitory influences than rT3-generating activity; and (d) in cord blood leukocytes, the putative enzymes catalyzing T3 and rT3 generation appear to be functionally intact under the experimental conditions employed.
Alterations in IRF1/IRF2 expression in acute myelogenous leukemia
Authors: H.D. Preisler, S. Perambakam, B. Li, W.T. Hsu, P. Venugopal, S. Creech, S. Sivaraman, N. Tanaka
Journal: American Journal of Hematology (2001)

Abstract The interferon response genes 1 and 2 have been shown to be involved in the regulation of differentiation and proliferation of cells of the myeloid series, with the former functioning as an anti‐oncogene and the latter as an oncogene. In the study described here, the levels of expression of these two genes and the ratio of their expression were compared in AML and normal marrow. The ratio of gene expression was significantly less in AML marrow cells as compared to normal marrow cells [med ratio = 1.33 vs. 2.97, P = 0.003]. While the expression ratio was unaffected by the presence or absence of either ras or fms mutations, p53 mutations were associated with higher IRF1:IRF2 expression ratios that wt p53 genes [med = 1.701 vs. 1.135, P = 0.014]. Given the functional characteristics and the competitive nature of these two genes, it is possible that leukemic transformation is associated with a fall in IRF1:IRF2 ratios. Finally, the administration of IL4 can result in the normalization of the IRF1:IRF2 ratio in the marrow cells of some patients with AML. Am. J. Hematol. 68:23–31, 2001. © 2001 Wiley‐Liss, Inc.
Case of Twins; One White, One Black.
Authors: F. B. Heisordt
Journal: JAMA (1894)

Wayne Co. House, Eloise, Mich., Nov. 7, 1894. <h3>To the Editor:</h3> —In reply to yours of November 2, I will say that twins were born, one African and one white child. The colored baby lived. The mother is a light-haired German woman, and I learn from her that the father was "a nigger born in slavery"—probably his father was some slave driver, at least he must have been a white man. "Breeding back," as the horseman says, seems to be applicable in this case. Yours very truly,
A CASE OF CONGENITAL DEFICIENCY OF THE LACHRYMAL SECRETION
Authors: J. V. Solomon
Journal: BMJ (1854)

If it were not that a change of nomenclature alwavs eutails a degree of incouvenieuce, I should be induced to rugge6L tihe ubadonment of the term lachrymal xeroma, as conveyin, ani erroneous ideac oR the iwtuel state of tLe ocular surface, anud the substitution, of lachr)znal acrinis-& priv., I p1cd, to separate-a paucity or non*secretion of tears.Audl I would limit the word xerouza to that diseased coudition of the ColjjulintivA which is attended by a loss of the characteriitics of mucous mnembrajit, on 16 July
UPSTREAM VERSUS DOWNSTREAM ADMINISTRATION OF GLYCOPROTEIN IIB/IIIA INHIBITORS IN PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROMES: A META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Alessandro Sciahbasi, Giuseppe Biondi Zoccai, Enrico Romagnoli, Ernesto Lioy
Journal: Journal of the American College of Cardiology (2010)
Early-life Exposure to Organophosphate Pesticides and Pediatric Respiratory Symptoms in the CHAMACOS Cohort
Authors: Rachel Raanan, Kim G. Harley, John R. Balmes, Asa Bradman, Michael Lipsett, Brenda Eskenazi
Journal: Environmental Health Perspectives (2014)

Background: Although pesticide use is widespread, the possible effect of early-life exposure to organophosphate (OP) on pediatric respiratory health is not well described.Objectives: We investigated the relationship between early-life exposure to OPs and respiratory outcomes.Methods: Participants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5–5 years). Childhood DAP concentrations were estimated by the area under curve (AUC). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. We used generalized estimating equations (GEE) to examine associations of prenatal and childhood DAP concentrations with repeated measures of respiratory symptoms and exercise-induced coughing at 5 and 7 years of age, adjusting for child's sex and age, maternal smoking during pregnancy, secondhand tobacco smoke, season of birth, PM2.5, breastfeeding, mold and cockroaches in home, and distance from highway.Results: Higher prenatal DAP concentrations, particularly DE, were nonsignificantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age [adjusted odds ratio (aOR) per 10-fold increase = 1.44; 95% CI: 0.98, 2.12]. This association was strongest with total DAP and DE from the second half of pregnancy (aOR per 10-fold increase = 1.77; 95% CI: 1.06, 2.95; and 1.61; 95% CI: 1.08, 2.39, respectively). Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age (total DAPs: aOR per 10-fold increase = 2.53; 95% CI: 1.32, 4.86; and aOR = 5.40; 95% CI: 2.10, 13.91, respectively).Conclusions: Early-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood.Citation: Raanan R, Harley KG, Balmes JR, Bradman A, Lipsett M, Eskenazi B. 2015. Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort. Environ Health Perspect 123:179–185; http://dx.doi.org/10.1289/ehp.1408235
Functional Significance of Prorenin Internalization in the Rat Heart
Authors: Jörg Peters, Raphaela Farrenkopf, Susanne Clausmeyer, Jutta Zimmer, Surasak Kantachuvesiri, Matthew G.F. Sharp, John J. Mullins
Journal: Circulation Research (2002)

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2 d renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.
Aggressive behavior and serum testosterone concentration during the maturation process of male mice: the effects of fetal exposure to bisphenol A.
Authors: Keisuke Kawai, Takehiro Nozaki, Hiroaki Nishikata, Shuji Aou, Masato Takii, Chiharu Kubo
Journal: Environmental Health Perspectives (2002)

The relationship between exposure to endocrine-disrupting chemicals (EDs) and risk to reproductive organs is well documented, but the influence of EDs on behavioral development has not been studied. In this study we evaluated the effect of fetal exposure to bisphenol A, which mimics estrogenic activity, on aggressive behavior and hormonal change in male mice. On gestation days 11-17, female mice were fed bisphenol A at 2 ng/g or 20 ng/g of body weight (environmentally relevant concentration). Aggression rating and blood sampling of the offspring were done at 8, 12, and 16 weeks of age. Aggression scores increased significantly (p < 0.01) at 8 weeks of age in male mice exposed to bisphenol A at both the 2 ng/g and 20 ng/g concentrations compared with a control group, but no difference was found after 12 weeks. Relative testis weight (per gram of body weight) was significantly lower at 8 and 12 weeks in mice treated with 2 ng/g than in controls (p < 0.05) and was significantly lower at 12 weeks in mice treated with 20 ng/g than in controls (p < 0.01). The serum testosterone concentration in treated mice was not significantly different from that in controls. These results demonstrate that bisphenol A temporarily activated aggressive behavior in mice at 8 weeks of age and that low doses of bisphenol A interfered with the normal development of reproductive organs. The mechanism activating this aggressive behavior was not elevated testosterone concentration.
BILE PHYSIOLOGY AND THERAPY
Authors: E. J. TEETER
Journal: JAMA (1946)

Before the time of Aristotle and probably previous to the time of Hippocrates it was said that there were four "humors" of the body, i. e. blood, phlegm, yellow bile and black bile. Since two of these four humors were thought to be bile, our predecessors apparently attached much importance to this natural body product. These early commentators certainly were correct in this belief. However, it has required the more modern methods of science to give us a fairly clear concept of bile. There are many gaps in our knowledge, but the combined work of physiologists, pharmacologists and chemists during the past several years has served to clarify our understanding of the physiology of bile and the use of bile in therapy. <h3>FORMATION OF BILE</h3> Bile is a product of the liver. One is safe in saying that the production of bile is a monopoly of the liver. Whether bile