tbuckley/cabot-search huggingface dataset:
Tazarotene-first of a new generation of receptor-selective retinoids
Authors: R.A.S. CHANDRARATNA
Journal: British Journal of Dermatology (1996)

Tazarotene is a topically applied retinoid that targets the skin, the site of the fundamental defect(s) in psoriasis, modulating the major causes of the disease and achieving sustained efficacy. In vitro, binding of tazarotenic acid has been demonstrated to retinoic acid receptors (RARs), the probable molecular target of retinoid action in adult human skin, but not to retinoid X receptors (RXRs). In gene activation assays, tazarotene is selective for the RAR beta and RAR gamma subtypes. This selectivity could theoretically limit undesirable effects at the receptor level. In vitro, animal and clinical evidence reveals that topical tazarotene modulates all three pathogenic factors in psoriasis: abnormal keratinocyte differentiation, hyperproliferation, and increased expression of inflammatory markers. Tazarotene is minimally absorbed systemically after topical administration. Tazarotene is rapidly metabolized by esterase metabolism to its active free-acid form, tazarotenic acid, which has a relatively short elimination half-life (1-2 h). The pharmacokinetic profile of tazarotenic acid is predictable, with no significant accumulation. In preclinical toxicity studies, high topical doses produced only reversible topical irritation, and lower doses were well tolerated. Topical doses were neither carcinogenic nor teratogenic, had no effect on fertility or general reproduction, and were not phototoxic, sensitizing, or photoallergenic. The pharmacological selectivity of tazarotene and limited systemic exposure result in minimal systemic effects, while the lesser cytotoxic effects (relative to other retinoids) result in reduced local effects.
Controlled Neuropsychological Investigation of Patients with Neurotic Excoriations
Authors: Henry Nielsen, Kjeld Fruensgaard, Anders Hjortsh&oslash;j
Journal: Psychotherapy and Psychosomatics (1980)

On the basis of preliminary empirical findings and the pertinent neuropsychological literature the following hypothese are put forward: (1) Because of a certain amount of abreaction (scratching), patients with neurotic excoriations will obtain higher scores in tests of verbal learning and long-term memory than "common' neurotics but probably lower scores in such tests than a group of "normal' subjects. (2) Visual long-term memory is relatively impaired both in patients with neurotic excoriations and in "common' neurotics compared to a "normal' group. (3) Performances IQ for both patient groups mentioned will be relatively low compared to verbal IQ. - The first and second of these suppositions were confirmed but not the third.
Cholinergic mechanism in the large cat cerebral artery.
Authors: T J Lee
Journal: Circulation Research (1982)

The isolated cat cerebral arteries (basilar, middle cerebral, anterior cerebral, and internal carotid) were studied in vitro. ACh at low concentration (3 x 10(-8) to 3 x 10(-6) M) induced relaxation, and at high concentration (10(-5) to 3 x 10(-3) M) induced constriction of the arteries with endothelial cells. In contrast, concentration of any magnitude (10(-6) to 3 x 10(-3) M) induced constriction exclusively in arteries without endothelium. Atropine (3 x 10(-6) to 3 x 10(-5) M) blocked and physostigmine (3 x 10(-6) M) potentiated both ACh-induced relaxation and constriction. These results suggest that the relaxation induced by exogenous ACh is solely dependent on the endothelial cells and that the primary effect of the direct action of ACh on the smooth muscle cells is constriction. Transmural nerve stimulation (TNS) induced a frequency-dependent relaxation in the arteries with or without endothelium. Neither atropine nor physostigmine affected the TNS-induced dilator response in either preparation. This, together with the wide separation between the nerve and endothelium in the vessel wall, suggests that ACh is not involved in TNS-induced vasodilation. Furthermore, the TNS-induced relaxation at any frequency is not smaller but greater in the arteries without endothelial cells than in those with endothelial cells. Blockade of the TNS-induced vasodilation by tetrodotoxin (TTX) or cold storage denervation did not prevent the arteries from relaxing in response to ACh or methacholine (MCh). It is suggested that the TNS-induced vasodilation is independent of the endothelial cells and that the vasodilation is due to the direct action of a yet-to-be identified dilator transmitter on the smooth muscle cells. Results of the present study support our previous finding that, in the cat cerebral artery. ACh is more likely to be a constrictor transmitter than a dilator transmitter.
Whooping cough immunization.
Authors: J Cameron
Journal: BMJ (1970)

liary basis?If equipment is left in a house under such circumstances where does the equipment come from for the next patient or the next three or four patients all within 24 hours?We are told that general practitioners "treat many of such patients at home with satisfactory and safe results."Those of us with experience of coronary care units know that the arrest case cannot be anticipated.We know that a few lives are saved.I doubt if these lives would be saved under the treatment at home methods encouraged by Dr. Fry.They require more than just a trained nurse or technician sitting at the bed side.
The NASA Syndrome Revisited-Reply
Authors: Bruce W. Spurlock
Journal: JAMA (1992)

<h3>In Reply.</h3> —I appreciate Dr Merrill's response as a surgeon to my letter on the NASA syndrome. My experience with the NASA syndrome is not limited to one hospital or one particular group of physicians, however. In discussing this situation with physicians throughout the United States, I have found that the diagnosis of the NASA syndrome is common. My letter was intended primarily to call attention to a communication problem among physicians that can affect patient care. My concern is the way any physician uses terminology to help other physicians solve clinical problems. Internists also use phrases that are similar to the NASA syndrome. Little benefit is obtained when a physician merely relates a chief complaint in an assessment without giving any further explanation or analysis. In both oral and written communication to colleagues, physicians of all specialties and subspecialties should explain what diagnosis or diagnostic possibilities are most probable
RETRACTED: Intramuscular delivery of 3D aggregates of HUVECs and cbMSCs for cellular cardiomyoplasty in rats with myocardial infarction
Authors: Ding-Yuan Chen, Hao-Ji Wei, Wei-Wen Lin, Kun-Ju Lin, Chieh-Cheng Huang, Cheng-Tse Wu, Shiaw-Min Hwang, Yen Chang, Hsing-Wen Sung
Journal: Journal of Controlled Release (2013)
Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.
Authors: T W Meade, R Chakrabarti, A P Haines, W R North, Y Stirling
Journal: BMJ (1979)

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.
TRANSPOSED HEART.ANOMALY REVEALED BY BULLET WOUND THROUGH NORMAL LOCATION.
Authors: JAMES A. ROLLS
Journal: JAMA (1906)

The following unusual case occurred recently in my practice: <h3>Patient.</h3> —A boy, aged 16, was shot in the left breast. <h3>Examination.</h3> —I found the patient with a rapid pulse of fairly good quality, showing moderate signs of shock, with a bullet wound over the fifth rib, on the left side, 1½ inches inside the mammary line. An hour previously a friend, in handing to him a 22-caliber rifle, had accidentally discharged it when the muzzle was almost touching his breast, and directed slightly outward and upward. It seemed that the heart could not have escaped. No apex beat was visible, and to my surprise none could be felt, nor could any sound be heard in the usual locality. Percussion gave moderately dull note at the fifth rib, passing into dulness lower down and continuing the costal margin. Examination of the right side cleared up the anomaly, as there was no
Current Concepts of Infectious Diseases
Authors: Leslie Barton
Journal: JAMA (1978)

<i>Current Concepts of Infectious Diseases</i>is a multiauthored, multiedited volume derived from the presentations at the 1976 conference on advances in infectious diseases, given by the Department of Medicine of the University of Virginia School of Medicine. The book is divided into seven major sections, starting with antimicrobials and encompassing endocarditis, infections in impaired hosts, infectious disease prophylaxis, viral diseases, nosocomial infection, and hepatitis. The book is brief (277 pages), well indexed, and clearly printed. The chapters, however, are of variable quality. The chapter devoted to bacterial meningitis would benefit from more specific data, especially with respect to morbidity and mortality; and, considering the plethora of literature on the subject, the references are meager. On the other hand, the chapters on infectious endocarditis, neutrophils, and cell-mediated immunity are excellent in their breadth, clarity, illustrations, and references. Although copyrighted in 1977, there are inevitably some areas that have changed since the
A New X-ray Technic for Visualization of the Heart and Great Vessels
Authors: FERDINAND F. MCALLISTER, CLAUD S. BECK
Journal: Circulation (1950)

A new roentgenographic technic is described, utilizing a balloon fitted over the opening of a cardiac catheter; the latter may then be threaded into the heart chambers via a superficial vessel. Momentary inflation of the balloon with air or a contrast medium outlines the heart chambers for x-ray exposure.
Two Cases of Subclavian Aneurysm Associated with Cervical Rib
Authors: A. Naylor
Journal: BMJ (1958)

ANTICHOLINESTERASE POISONING MBROFurther work is required before a standardized treatment can be recommended, and in any case atropine is still essential.Some of the common organophosphate insecticides, however, which themselves are relatively non-toxic to man are slowly converted in the body to very toxic sub- stances-for example, parathion is converted into the very poisonous paraoxon.Repeated dosing with P2S and atropine may therefore be necessary to counteract the effects of suc- cessive amounts of, for example, paraoxon, as this is syn- thesized in vivo from the reservoir of parathion.P2S tends to produce small quantities of cyanide when heated in aqueous solution, the cyanide formation being greater in neutral (pH 7) than in acid (pH 4N solution.Solid P2S decomposes when heated at 1500 C. It cannot, therefore, be sterilized by heat either as the solid or in solution.However, Seitz filtration has proved satisfactory.At room temperature aqueous solutions are stable for three months provided that the pH is kept at 4. The solid appears to be stable indefinitely.P2S plus atropine is unlikely to be effective against poisoning by phosphates in which a diaminoalkyl group is directly connected with the phosphorus atom as in O.M.
Isothiocyanates Reduce Mercury Accumulation via an Nrf2-Dependent Mechanism during Exposure of Mice to Methylmercury
Authors: Takashi Toyama, Yasuhiro Shinkai, Akira Yasutake, Koji Uchida, Masayuki Yamamoto, Yoshito Kumagai
Journal: Environmental Health Perspectives (2011)

Background: Methylmercury (MeHg) exhibits neurotoxicity through accumulation in the brain. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) plays an important role in reducing the cellular accumulation of MeHg.Objectives: We investigated the protective effect of isothiocyanates, which are known to activate Nrf2, on the accumulation of mercury after exposure to MeHg in vitro and in vivo.Methods: We used primary mouse hepatocytes in in vitro experiments and mice as an in vivo model. We used Western blotting, luciferase assays, atomic absorption spectrometry assays, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, and we identified toxicity in mice based on hind-limb flaccidity and mortality.Results: The isothiocyanates 6-methylsulfinylhexyl isothiocyanate (6-HITC) and sulforaphane (SFN) activated Nrf2 and up-regulated downstream proteins associated with MeHg excretion, such as glutamate-cysteine ligase, glutathione S-transferase, and multidrug resistance–associated protein, in primary mouse hepatocytes. Under these conditions, intracellular glutathione levels increased in wild-type but not Nrf2-deficient primary mouse hepatocytes. Pretreatment with 6-HITC and SFN before MeHg exposure suppressed cellular accumulation of mercury and cytotoxicity in wild-type but not Nrf2-deficient primary mouse hepatocytes. In comparison, in vivo administration of MeHg to Nrf2-deficient mice resulted in increased sensitivity to mercury concomitant with an increase in mercury accumulation in the brain and liver. Injection of SFN before administration of MeHg resulted in a decrease in mercury accumulation in the brain and liver of wild-type, but not Nrf2-deficient, mice.Conclusions: Through activation of Nrf2, 6-HITC and SFN can suppress mercury accumulation and intoxication caused by MeHg intake.
Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the Internet
Authors: Giuseppe Argenziano, H.Peter Soyer, Sergio Chimenti, Renato Talamini, Rosamaria Corona, Francesco Sera, Michael Binder, Lorenzo Cerroni, Gaetano De Rosa, Gerardo Ferrara, Rainer Hofmann-Wellenhof, Michael Landthaler, Scott W. Menzies, Hubert Pehamberger, Domenico Piccolo, Harold S. Rabinovitz, Roman Schiffner, Stefania Staibano, Wilhelm Stolz, Igor Bartenjev, Andreas Blum, Ralph Braun, Horacio Cabo, Paolo Carli, Vincenzo De Giorgi, Matthew G. Fleming, James M. Grichnik, Caron M. Grin, Allan C. Halpern, Robert Johr, Brian Katz, Robert O. Kenet, Harald Kittler, Jrgen Kreusch, Josep Malvehy, Giampiero Mazzocchetti, Margaret Oliviero, Fezal zdemir, Ketty Peris, Roberto Perotti, Ana Perusquia, Maria Antonietta Pizzichetta, Susana Puig, Babar Rao, Pietro Rubegni, Toshiaki Saida, Massimiliano Scalvenzi, Stefania Seidenari, Ignazio Stanganelli, Masaru Tanaka, Karin Westerhoff, Ingrid H. Wolf, Otto Braun-Falco, Helmut Kerl, Takeji Nishikawa, Klaus Wolff, Alfred W. Kopf
Journal: Journal of the American Academy of Dermatology (2003)
Tumor necrosis factor downregulates granulocyte-colony-stimulating factor receptor expression on human acute myeloid leukemia cells and granulocytes.
Authors: O Elbaz, L M Budel, H Hoogerbrugge, I P Touw, R Delwel, L A Mahmoud, B Löwenberg
Journal: Journal of Clinical Investigation (1991)

Tumor necrosis factor (TNF) inhibits granulocyte-colony-stimulating factor (G-CSF)-induced human acute myeloid leukemia (AML) growth in vitro. Incubation of blasts from three patients with AML in serum-free medium with TNF (10(3) U/ml), and subsequent binding studies using 125I-G-CSF reveal that TNF downregulates the numbers of G-CSF receptors by approximately 70%. G-CSF receptor numbers on purified blood granulocytes are also downmodulated by TNF. Downregulation of G-CSF receptor expression becomes evident within 10 min after incubation of the cells with TNF at 37 degrees C and is not associated with an apparent change of the dissociation constant (Kd). The TNF effect does not occur at 0 degrees C and cannot be induced by IL-2, IL-6, or GM-CSF. TNF probably exerts its effect through activation of protein kinase C (PKC) as the TNF effect on G-CSF receptor levels can be mimicked by 12-O-tetradecanoylphorbol-13- acetate. The PKC inhibitor Staurosporine (Sigma Chemical Co., St. Louis, MO) as well as protease inhibitors can completely prevent G-CSF receptor downmodulation. Thus, it appears TNF may act as a regulator of G-CSF receptor expression in myeloid cells and shut off G-CSF dependent hematopoiesis. The regulatory ability of TNF may explain the antagonism between TNF and G-CSF stimulation.
Von Willebrand's Disease and the Molecular Pathology of Hemostasis
Authors: Ralph L. Nachman
Journal: New England Journal of Medicine (1977)

Over 50 years ago, Eric von Willebrand1 described a severe hereditary bleeding disorder in an Äland Island family. The abnormality, which he referred to as "pseudo hemophilia," was characterized by a prolonged bleeding time and was associated with an autosomal inheritance pattern. Approximately 25 years later, Alexander and Goldstein2 made a major advance in the unravelling of von Willebrand's disease when they described the now well recognized dual hemostatic defect: reduced factor VIII procoagulant activity (antihemophilic factor) and a prolonged bleeding time. More recently, there has been an explosion of knowledge of the factor VIII system, and with this knowledge . . .
THE ETIOLOGY OF HYPERTENSION DUE TO COMPLETE RENAL ISCHEMIA
Authors: Myron Prinzmetal, Harvey A. Lewis, Sidney D. Leo
Journal: The Journal of Experimental Medicine (1940)

1. Perfusates of totally ischemic kidneys of cats contain a pressor substance which is not present in the perfusates of normal kidneys, ischemic hind limbs, or ischemic gravid uteri. 2. The pressor material in ischemic renal perfusates originates directly in the kidney as a result of complete ischemia. 3. The pressor principle contained in ischemic renal perfusates is the cause of the hypertension which follows the reestablishment of circulation in completely ischemic kidneys, since perfusates of unreleased completely ischemic kidneys contain more pressor material than perfusates of released ischemic kidneys of the same animal. 4. The pressor principle in ischemic renal perfusates is presumed to be renin for the following reasons, (a) Both substances are destroyed by boiling, (b) Both substances induce tachyphylaxis. (c) The configuration of both pressor curves is identical, (d) The pressor action of both is not reversed by 933F, proving they are not epinephrine-like substances. (e) When incubated with plasma, both form a heat-stable pressor substance. (f) The pressor effect of both is uninfluenced by a previous injection of cocaine, (g) Unreleased, completely ischemic kidneys yield more pressor material on extraction than do released ischemic kidneys of the same animal. 5. The perfusates of blood-free ischemic kidneys contain more renin than those of blood-filled ischemic kidneys. 6. A method is described by which the power of various substances to inhibit or enhance the production of renin in the ischemic kidney may be tested. 7. A small amount of the heat-stable pressor substance, presumably angiotonin or hypertensin, is formed by the reaction of the pressor material (renin) and plasma in the vessels of the kidney during the period of complete ischemia.
Corrigendum to “Both Immediate and Delayed Intracavernous Injection of Autologous Adipose-derived Stromal Vascular Fraction Enhances Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury” [Eur Urol 2012;62:720–7]
Authors: Xuefeng Qiu, Thomas M. Fandel, Ludovic Ferretti, Maarten Albersen, Hazem Orabi, Haiyang Zhang, Guiting Lin, Ching-Shwun Lin, Tania Schroeder, Tom F. Lue
Journal: European Urology (2012)
Helper activity is required for the in vivo generation of cytotoxic T lymphocytes
Authors: J-A Keene, J Forman
Journal: The Journal of Experimental Medicine (1982)

B6.T1a(a) (Qa-1(a)) mice that are primed in vivo and restimulated in vitro with Qa-1 congenic spleen cells from B6 (Qa-1(b)) animals are unable to generate anti-Qa-1(b) cytotoxic T lymphocytes (CTL). This nonresponsive pattern was observed regardless of the route of immunization or the time of testing in vitro. Although B6.T1a(a) mice are nonresponders to Qa-1(b) when presented on B6 cells, these mice can generate anti-Qa-1(b) CTL when primed in vivo with Qa-1 and H-Y alloantigens (females primed with B6 male cells) or Qa-1 and minor-H- alloantigens (primed with sex-matched A.BY cells). Therefore, the inability to generate anti-Qa-1(b) CTL is due to a lack of helper or accessory antigens on B6 immunizing cells obligatory during in vivo priming, rather than an absence of anti-Qa-1(b) CTL precursors (CTL-P). Demonstration that the additional determinants required during in vivo priming actually function as carrier or helper determinants was shown by the requirement for linked recognition of Qa-1 and the helper determinants (H-Y) in vivo, and the fact that H-Y was not present on susceptible target ceils. Animals primed in vivo with H-Y only could not generate anti-Qa-1 CTL activity when challenged in vitro with both Qa-1 and H-Y, indicating that recognition of the helper determinant causes in vivo priming of CTL-P rather than generating helper activity that might activate unprimed CTL-P in vitro. Whereas unprimed peripheral CTL-P require the presence of both Qa-1 (CTL) and H-Y (helper) determinants for successful in vivo priming, helper determinants were not required in vitro because primed CTL-P from B6.T1a(a) mice could be driven to CTL in vitro using sex-matched B6 stimulator cells. The generation of anti-Qa-1(b) CTL is under immune response (Ir) gene control because F(1) mice, obtained by crossing responder A/J with nonresponder B6.T1a(a) animals, generated CTL to the Qa-1(b) alloantigen when presented on B6 spleen cells. Progeny testing of backcross mice further demonstrated that the Ir gene(s) is linked to the H-2 complex. These data indicate that an H-2-linked Ir gene controls the recognition of helper determinants required for CTL priming in vivo. These helper determinants can be distinguished from CTL determinants and both must be recognized together for successful priming of CTL-P.
SURGERY OF THE GALLBLADDER AND THE BILIARY DUCTS
Authors: E. S. JUDD
Journal: JAMA (1918)

Infection and malignancy are conditions which enter into the etiology of surgical lesions of the biliary tract. The contention that infection enters this region much more often by way of the general circulation than was formerly believed is supported by the results of experimental work on animals and also by the fact that infections in this tract are, in many instances, only a part of a more general infection, as is frequently shown by the presence of lesions existing in the appendix, duodenum or stomach at the same time. Whether the infection is primary in any one of these foci and from it distributed to the other regions, or whether infection begins at the same time at several different points, owing to organisms circulating in the blood stream, cannot be definitely decided. It is, however, of practical importance that surgical procedure for lesions of the biliary tract will usually involve