tbuckley/cabot-search huggingface dataset:
Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells
Authors: Robert Besch, Hendrik Poeck, Tobias Hohenauer, Daniela Senft, Georg Häcker, Carola Berking, Veit Hornung, Stefan Endres, Thomas Ruzicka, Simon Rothenfusser, Gunther Hartmann
Journal: Journal of Clinical Investigation (2009)

The retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I– and MDA-5–initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I– and MDA-5–mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis.
Glucose Phosphate Isomerase Deficiency as a Cause of Hydrops Fetalis
Authors: Yaddanapudi Ravindranath, Donald E. Paglia, Indira Warrier, William Valentine, Misae Nakatani, Richard A. Brockway
Journal: New England Journal of Medicine (1987)

ERYTHROCYTE enzymopathies are well-recognized causes of hemolytic anemia in newborn infants, but have rarely been implicated etiologically in hydrops fetalis or immediate neonatal death. Death occurred within a few hours of birth in only 4 of 260 cases recently reviewed by Matthay and Mentzer.1 One patient was deficient in glucose phosphate isomerase (D-glucose-6-phosphate ketol-isomerase, E.C. 5.3.1.9),2 two others in pyruvate kinase,3 , 4 and another in triosephosphate isomerase.5 Hydrops fetalis is also rare in association with the more common deficiencies of glucose-6-phosphate dehydrogenase. In two cases, severe anemia and hydrops in an infant were attributed to maternal ingestion of oxidants (sulfisoxazole,6 fava . . .
Effectiveness and Efficiency in Health Care
Authors: John Lister
Journal: New England Journal of Medicine (1972)

THERE have been few objective appraisals of the National Health Service partly because of the political emotions that are aroused when there is any suggestion that it may have any serious imperfection and partly because of the medical emotions that are aroused when there is any suggestion that its improvement might require an alteration of the attitude of the medical profession. In his Rock Carling monograph1 just published by the Nuffield Provincial Hospitals Trust, Dr. A. L. Cochrane, director of the Medical Research Council Epidemiology Unit at Cardiff, had no inhibitions in his random reflections on the effectiveness and efficiency . . .
Respiratory Failure in the Acute Case of Poliomyelitis
Authors: A. B. Christie
Journal: BMJ (1954)

The pathological and clinical (may I even say surgical ?) approach has thus furnished us with a working hypothesis on which the function of the thymus gland may eventually be elucidated.There are still many difficulties in the way of a final solution, and progress is likely to be slow.It may be thought safer to return for the present to Galen's belief that the thymus is just a cushion to protect the great vessels from contact with the sternum.This would certainly save us all a great deal of trouble.
The Xylosyltransferase I Gene Polymorphism c.343G&amp;gt;T (p.A125S) Is a Risk Factor for Diabetic Nephropathy in Type 1 Diabetes
Authors: Sylvia Schön, Christian Prante, Claudia Bahr, Lise Tarnow, Joachim Kuhn, Knut Kleesiek, Christian Götting
Journal: Diabetes Care (2006)

Xylosyltransferase I (XT-I) is the chain-initiating enzyme in the biosynthesis of proteoglycans in basement membranes. It catalyzes the transfer of xylose to selected serine residues in the core protein. The XYLT-II gene codes for a protein highly homologous to XT-I. Proteoglycans are important components of basement membranes and are responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which results in microvascular complications. Thus, genetic variations in the xylosyltransferase genes might be implicated in the initiation and progression of these complications.Genotyping of four genetic variations in the genes XYLT-I and XYLT-II was performed in 912 type 1 diabetic patients (453 with and 459 without diabetic nephropathy) using restriction fragment-length polymorphism.The distribution of the c.343G>T polymorphism in XYLT-I is significantly different between patients with and without diabetic nephropathy (P = 0.03). T-alleles were more frequent in patients with diabetic nephropathy (odds ratio 2.47 [95% CI 1.04-5.83]). The allelic frequencies of the other investigated XYLT-I and XYLT-II variations (XYLT-I: c.1989T>C in exon 9; XYLT-II: IVS6-9T>C and IVS6-14_IVS6-13insG in intron 5; and c.2402C>G: p.T801R in exon 11) were not different between patients with and without diabetic nephropathy.The XYLT-I c.343G>T polymorphism contributes to the genetic susceptibility to development of diabetic nephropathy in type 1 diabetic patients.
Parse Analysis II — A Revised Model That Accounts for<i>phi</i>
Authors: P J Davis, R I Gregerman
Journal: New England Journal of Medicine (1995)

In 1969 our laboratories described a quantitative method for evaluating academic careers that was based on a concept called parse analysis.1 With the help of two postdoctoral fellows whose names were negligently omitted from the original report*, we coaxed the concept of parse into existence in response to the burgeoning problems of multiauthorship of papers and perceived logarithmic differences (PLDs) in the quality of published papers. In its original iteration, parse analysis assigned decimal values to the real contributions of investigators to a multiauthored paper — e.g., 0.04 or 0.37. The rationale was that embarrassingly low parse values — . . .
Candida Endocarditis Of the Tricuspid Valve
Authors: Giora Mavligit
Journal: JAMA (1970)

<h3>To the Editor.—</h3> It has been suggested that<i>Candida</i>organisms are ordinarily incapable of initiating infection on a normal valve.<sup>1</sup>Review of the literature revealed five cases of<i>Candida</i>endocarditis that appeared to have solely involved the tricuspid valve.<sup>2-6</sup>An underlying endocardial lesion invariably preceded these fungal infections. In this respect, our own case was exceptional. <h3>Report of a Case.—</h3> Endocarditis was discovered postmortem in a 77-year-old man with chronic obstructive lung disease of 15 years' duration. There was no past history of congenital heart disease, rheumatic fever, cardiac catheterization, trauma, or surgery of the heart, bacterial endocarditis, diabetes mellitus, or steroid treatment—all known to be predisposing factors in<i>Candida</i>endocarditis. However, recurrent pulmonary infections with a variety of bacterial organisms required treatment with multiple antibiotics, including penicillin, streptomycin, ampicillin, and cephalothin sodium. His terminal admission was prompted by an acute cardiorespiratory decompensation of five days' duration. Cyanosis,
Educating Tomorrow's Doctors
Authors: C. H. William Ruhe
Journal: JAMA (1965)

Soon after a revised program of medical education was introduced at Western Reserve, the present study was undertaken as one means of determining the effectiveness of the program. Twenty students were observed closely throughout their school career. A brief profile is given for each of the 20, and the thoughts, actions, and reactions of each are described at intervals in their progress through the school. There is a brief note on each one five years later. There is some resemblance to the study at the University of Kansas published under the title<i>Boys in White</i>, which observed the development of students as they progressed through medical school. However, in<i>Boys in White</i>the students were studied as a group moving in a social system (the medical school), and the students' progress was viewed as a social-psychological phenomenon. In the present volume the 20 students are followed closely as individuals. While
STUDY OF THE CLASSIFICATION OF MENINGOCOCCI
Authors: Augustus B. Wadsworth, Ruth Gilbert, Alice Hutton
Journal: The Journal of Experimental Medicine (1921)

The meningococcus, like some other pathogenic species, varies in its agglutination in immune serum, some strains being readily agglutinable while others agglutinate with difficulty in their homologous serum as well as in heterologous serums. The different strains appear to vary also in their action as antigens. In order to secure representative strains, therefore, it was thought necessary to consider the antigenic action as well as the agglutinability of the cultures.
A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients
Authors: N.C.T. Kong, J. Beran, S.A. Kee, J.L. Miguel, C. Sánchez, J.-M. Bayas, A. Vilella, F. Calbo-Torrecillas, E. López de Novales, K. Srinivasa, M. Stoffel, B. Hoet
Journal: Kidney International (2007)
Residual Oil Fly Ash Amplifies Allergic Cytokines, Airway Responsiveness, and Inflammation in Mice
Authors: STEPHEN H. GAVETT, SHARON L. MADISON, MICHAEL A. STEVENS, DANIEL L. COSTA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Particulate matter (PM) air pollution may increase symptom severity in allergic asthmatics. To examine possible interaction, or greater than additive responses, between PM effects and allergic responses, an ovalbumin-sensitized and challenged (OVA) mouse model of allergic airways disease was utilized. After challenge, mice were intratracheally instilled with saline vehicle or 3 mg/kg (approximately 60 microg) residual oil fly ash (ROFA), a transition metal-rich emission source PM sample. Physiological and inflammatory responses were examined 1, 3, 8, and 15 d later. In response to intravenously administered methacholine, ROFA increased total respiratory system resistance and decreased compliance 1 d after exposure, whereas effects of OVA lasted at least 15 d after exposure. Significant interactions between OVA and ROFA were mainly observed 8 d after challenge and exposure, especially with respect to compliance. A strong interaction (p < 0.01) between OVA and ROFA exposure resulted in 8-fold (1 d) and 3-fold (3 d) increases in bronchoalveolar lavage (BAL) fluid eosinophil numbers. A similarly strong interaction (8-fold) was observed in BAL fluid interleukin-4 (IL-4) 1 d after challenge and exposure. Significant though less strong interactions were also found with respect to IL-4 and IL-5 by 3 d postchallenge/exposure. This study shows that allergen challenge and exposure to emission source particulate matter containing relatively high levels of transitions metals can interact to increase Th2 cytokine production, eosinophil recruitment, and airway hyperresponsiveness in previously sensitized mice.
Long-term survival following autologous and allogeneic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm
Authors: Tomohiro Aoki, Ritsuro Suzuki, Yachiyo Kuwatsuka, Shinichi Kako, Katsuya Fujimoto, Jun Taguchi, Tadakazu Kondo, Kinya Ohata, Toshiro Ito, Yoshimasa Kamoda, Takahiro Fukuda, Tatsuo Ichinohe, Kengo Takeuchi, Koji Izutsu, Junji Suzumiya
Journal: Blood (2015)
Seven-year follow-up of cardiovascular study and maximal exercise of Chinese men.
Authors: R A Bruce, Y L Pao, N Ting, B N Chiang, Y B Li, E R Alexander, R P Beasley, L D Fisher, S T Chiang
Journal: Circulation (1975)

A seven-year follow-up in 1973 of a prospective cardiovascular study of 1820 initially, healthy, middle-aged Chinese men of 40-59 years of age identified 1745 (95.9%) known survivors, 49 (2.7%) interim deaths, and 26 (1.4) who could not be traced. Of the survivors, 1462 (83.8%) were re-examined, 292 (16.7%) had another treadmill test of maximal exercise, and 283 (16.2%) failed to return for re-examination. On the basis of interim surveillance of hospital admissions, questionnaires and re-examination, a greater incidence of noncardiovascular events (338 or 18.6%) than evidence of cardiovascular disease (220 or 12.1%) was found while the majority (1021 or 56.1%) remained healthy. Total mortality was 0.29 for men under 50 and 0.76 per 100 person-years for men of 50 or more years of age. Only nine, or 18.4% of the deaths were due to cardiovascular causes, and unexpectedly for this population sample, only three were attributed to stroke. When cardiovascular morbidity was related to presence of ST depression after maximal exercise, to hypertension at rest by WHO criteria, to both findings, or to absence of either on initial intake examination, incidence increased from 2.3% for NEITHER group, to 5.7% for ST group, to 11.9% for HT group, and to 25.0% for BOTH groups. Re-examination revealed more evidence of cardiovascular disease than did surveillance of hospital admissions. Additional to effects of aging and mild adiposity, longitudinal changes in blood pressure and ST depression, increasing in the NEITHER group, but less frequent in the other groups, showed some evidence of regression toward the mean, as well as emerging disease and the confounding effects of uncontrolled treatment of hypertension in many. The potential for prediction of subsequent cardiovascular morbidity or mortality appeared stronger for hypertension than for postexertional ST depression, although the two were additive in this population, which is more prone to hypertension and stroke but now is developing clinical manifestations of coronary heart disease more frequently.
VITAMIN D IN THE TREATMENT OF ACNE VULGARIS
Authors: Abraham Doktorsky
Journal: JAMA (1933)

It is known that cases of acne vulgaris are improved temporarily by treatment with ultraviolet rays. The present work was based on the supposition that the activation of ergosterol in the skin by ultraviolet rays is the prime factor for this temporary relief in acne. We therefore attempted to alleviate acne by the direct ingestion of vitamin D in the form of viosterol. We ourselves were our first patients, since both of us have this condition. We started with a dosage of 10 drops a day of Mead's viosterol in oil 250 D and increased this during a period of two weeks to 20 drops a day. After continuing for a period of one month we observed by actual count of pustules a decrease of about 75 or 80 per cent. We considered these results satisfactory enough to warrant experimentation on a larger number of subjects. The subjects chosen for
Developmental differences in the expression of the cholera toxin sensitive subunit (Gs alpha) of adenylate cyclase in the rat small intestine.
Authors: I R Sanderson, Z Xu, S W Chu, Q Y Xie, L J Levine, W A Walker
Journal: Gut (1996)

BACKGROUND: The stimulatory guanosine triphosphate (GTP) binding protein alpha subunit (Gs alpha) of adenylate cyclase is the target protein for cholera toxin. AIMS/METHODS: The expression of this signal transducer was analysed in the small intestine of developing rats by RNA transfer (northern blot) analysis by immunoblotting, and by ADP-ribosylation of membrane proteins. RESULTS: Intestinal Gs alpha mRNA (about 1.9 kb) was increased in the neonate compared with the adult rat. Two isoforms of Gs alpha proteins, a 45,000 and a 52,000 form, were expressed in the small intestinal epithelial cell and both were ADP-ribosylated by cholera toxin. A significant increase in the larger isoform (52,000) and in its ribosylation was noted in the 2 week old suckling compared with post-weaned older animals. The protein content or ribosylation of the smaller form (45,000) did not significantly change with age. CONCLUSION: These data show that a developmental decline of intestinal Gs alpha expression seems to be, in part, regulated at the mRNA level. An increased Gs alpha expression in the immature intestine may help to explain a previously reported, dose dependent increased adenylate cyclase response and an increase in fluid secretion to cholera toxin in neonates compared with adults.
Keratin clumping in epidermolysis bullosa, Dowling-Meara type
Authors: I. Anton-Lamprecht
Journal: British Journal of Dermatology (1996)

Journal Article Keratin clumping in epidermolysis bullosa, Dowling‐Meara type Get access I. Anton‐Lamprecht I. Anton‐Lamprecht Institute for Ultrastructure Research of the Skin, Department of Dermatology, University of Heidelberg, Vosstrasse 2, D‐69115 Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 1, 1 January 1996, Pages 184–185, https://doi.org/10.1111/j.1365-2133.1996.tb07868.x Published: 01 January 1996
Illustration of an Obscure Joint-Affection
Authors: A. Fleischmann
Journal: BMJ (1859)

a strunious-looking child, delicate from birth, Wibout foule in oitlis ago, fell off a low wall.The injllly lie experienceed appeared insignificant, aintdI was forgotteni in a day or two, till six aeeks after the accident, lie slightly lhalted in his walk: the defect incieased, uintil lhe ceased to pult oneI leg before the otlier, andl prouressed by crawlin,g.Following the ad-vice thle ieceived, tlhe limijb xvas poulticed ; but the clhild
Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism
Authors: Alexandra Henrion-Caude, Cyril Flamant, Michel Roussey, Chantal Housset, Antoine Flahault, Anthony A. Fryer, Katarina Chadelat, Richard C. Strange, Annick Clement
Journal: Hepatology (2002)

Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. While the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is restricted to the biliary epithelium in the liver, recent findings indicate that CFTR modulates reduced glutathione (GSH) transport and that CFTR dysfunction creates an imbalance in the antioxidant defense. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. Because oxidative injury contributes to the development of liver disease, we hypothesized that 2 members of the GST superfamily, GSTM1 and GSTP1, which are expressed in the biliary epithelium, could influence the hepatic status in patients with CF. The potential impact of GSTM1 and GSTP1 gene polymorphisms was assessed in 106 children with CF (mean age, 11.5 years). Based on polymerase chain reaction/restriction fragment length polymorphism analysis, we found that the frequency of GSTP1-Ile 105 /Ile 105 genotype was significantly higher in patients with CF with liver disease than in those without ( P &lt; .03). Among the youngest patients, aged 6 years, GSTP1-Ile 105 /Ile 105 genotype was associated with a 8-fold increase in the risk of liver disease compared with other GSTP1 genotypes ( P = .002). No association between the GSTM1 genotype and liver status was documented. In conclusion, GSTP1-Ile 105 -encoding allele contributes to hepatic dysfunction in CF. Identification of this polymorphism may have prognostic value and prompt early treatment in patients with CF with an increased risk of liver disease.
An Introduction to Electrocardiography
Authors: S. A. Franzblau
Journal: JAMA (1964)

Out of the Republic of South Africa, from the University of Witwaterstrand in Johannesburg, has come this excellent and inexpensive addition to the primer-type texts on elementary principles of electrocardiography. It has been written and designed with the student in mind, and is ideally suited for use as a basic text for a short (five weeks or so) course in interpreting electrocardiograms. The typesetter's art has been given full sway with good use made of boldface type and italics to emphasize salient points. Each topic is then summarized in outline fashion. The line drawings and the reproductions of actual tracings are plentiful and of good quality. They are appropriately placed in the text so that very little page-turning is necessary to correlate text and related illustration. The references are of prime importance, and form a good springboard for more advanced study. The book is modern. It incorporates the more recent
SOME AXIOMS CONCERNING OCULAR ROTATIONS.
Authors: G. C. SAVAGE
Journal: JAMA (1906)

A convex sphere set in a concave hemisphere, the two having a common center, the one fitting in the other as shown in Figure 1, can be rotated on any one of its diameters, and only on a diameter, as an axis. The center of curvature, the point to which all the radii converge, is the center of rotation. The point on the surface at which the force is applied and the direction of the force determine what the plane of rotation shall be and fix the axis of rotation at right angles to this plane. This can be best understood by a study of Figure 1. A B D represents the concave hemisphere whose center is<i>c; a d b e</i>represents the convex sphere whose center is also<i>c</i>: If the force is so applied that<i>a b</i>shall be the rotation plane, the axis of rotation will
Experimental Toxoplasmosis in Chimpanzees
Authors: C. C. Draper, R. Killick-Kendrick, W. M. Hutchison, J. Chr. Siim, P. C. C. Garnham
Journal: BMJ (1971)

Two chimpanzees were given by mouth large numbers of viable oocysts of Toxoplasma gondii obtained from the faeces of experimentally infected cats. Before the experiment the first chimpanzee had a positive dye test reaction (1:250), an indication that it had undergone an earlier infection of toxoplasmosis; the serum antibody titres remained unchanged, no evidence of illness was found, and oocysts did not appear in its faeces during the subsequent six weeks. The second chimpanzee showed a negative dye test reaction before infection, and this converted to positive on the 7th day, rose to a peak on the 35th day, and remained high for six months. This animal appeared unwell during the first week, and on the 7th day its blood proved infective to mice; on the 40th day the lymph nodes became enlarged and biopsy specimens of a node and muscle in the 11th week were also infective to mice. No oocysts were passed in the faeces. The presumed cycle in the chimpanzee and in man and the relationships between Toxoplasma and Isospora are discussed.
ESR1 ligand-binding domain mutations in hormone-resistant breast cancer
Authors: Weiyi Toy, Yang Shen, Helen Won, Bradley Green, Rita A Sakr, Marie Will, Zhiqiang Li, Kinisha Gala, Sean Fanning, Tari A King, Clifford Hudis, David Chen, Tetiana Taran, Gabriel Hortobagyi, Geoffrey Greene, Michael Berger, José Baselga, Sarat Chandarlapaty
Journal: Nature Genetics (2013)