tbuckley/cabot-search huggingface dataset:
Anaphylactic reactions to formaldehyde in root canal sealant after endodontic treatment: four cases of anaphylactic shock and three of generalized urticaria
Authors: J. J. Braun, H. Zana, A. Purohit, J. Valfrey, Ph. Scherer, Y. Haïkel, F. de Blay, G. Pauli
Journal: Allergy (2003)
Expanding Circle of Inhibition: Small-Molecule Inhibitors of Bcl-2 as Anticancer Cell and Antiangiogenic Agents
Authors: Benjamin D. Zeitlin, Isaac J. Zeitlin, Jacques E. Nör
Journal: Journal of Clinical Oncology (2008)

The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis and obtain a survival advantage through aberrant expression of Bcl-2. The new and remarkably diverse class of drugs, small-molecule inhibitors of Bcl-2 (molecular weight approximately 400 to 800 Daltons), is examined herein. We present the activities of these compounds along with clinical observations, where available. The effects of Bcl-2 inhibition on attenuation of tumor cell growth are discussed, as are studies revealing the potential for Bcl-2 inhibitors as antiangiogenic agents. Despite an enormous body of work published for the Bcl-2 family of proteins, we are still learning exactly how this group of molecules interacts and indeed what they do. The small-molecule inhibitors of Bcl-2, in addition to their therapeutic potential, are proving to be an important investigative tool for understanding the function of Bcl-2.
Abstract LB-313: Development of a novel anti-MYC therapeutic with efficacy against liver and kidney cancers.
Authors: David I. Bellovin, Aleksey Yevtodiyenko, Stacey J. Adam, Hanan Fernando, Julia Arzeno, Meital Gabay, Dean W. Felsher
Journal: Cancer Research (2013)

Abstract One of the most attractive, yet elusive, targets for cancer therapy is the MYC oncogene. MYC is overexpressed in the majority of human cancers, and we and others have shown that suppression of this oncogene is sufficient to induce sustained tumor regression, a phenomenon known as oncogene addiction. However, no viable therapy has been developed as yet that targets this crucial regulator of the tumor phenotype. Here, we report the development of a novel antisense therapeutic that targets the MYC oncogene. This inhibitor can potently suppress MYC expression in primary tumors in vivo, as demonstrated by immunohistochemistry and real-time PCR. Importantly, we show that treatment with the anti-MYC drug significant reduces tumor onset and progression in transgenic mouse models of primary hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) cancer. We imaged tumor growth via MRI and utilized quantitative image analysis to demonstrate the inhibition of HCC and RCC progression, confirming our results on total tumor burden histologically after four weeks of drug treatment. Additionally, this antisense therapy against MYC can also attenuate the growth of human HCC cells in vivo, irrespective of the inducing oncogene. In contrast with other reported MYC inhibitors, our approach results in no discernible toxicity due to MYC suppression on any organs examined in the treated animals. Thus, we have established a novel therapy that directly inhibits the MYC oncogene, representing a potentially exciting advance in the field of targeted cancer therapeutics. Citation Format: David I. Bellovin, Aleksey Yevtodiyenko, Stacey J. Adam, Hanan Fernando, Julia Arzeno, Meital Gabay, Dean W. Felsher. Development of a novel anti-MYC therapeutic with efficacy against liver and kidney cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-313. doi:10.1158/1538-7445.AM2013-LB-313 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Opening of Potassium Channels
Authors: Egidijus Kevelaitis, Jacqueline Peynet, Christian Mouas, Jean-Marie Launay, Philippe Menasché
Journal: Circulation (1999)

Background —The tolerance of hibernating mammals to cold hypoxia is related to a factor similar to agonists of δ-opioid receptors. This study was designed to assess whether activation of these receptors could reproduce the protection conferred by ischemic preconditioning and whether such cardioprotection was similarly mediated by an opening of ATP-sensitive potassium (K ATP ) channels. Methods and Results —Thirty-two isolated rat hearts were arrested with and stored in Celsior at 4°C for 5 hours before being reperfused for 2 hours. They were divided into 4 equal groups. Group 1 hearts served as controls. In group 2, ischemic preconditioning was elicited by two 5-minute global ischemia periods interspersed with 5 minutes of reperfusion before arrest. In group 3, hearts were pharmacologically preconditioned with a 15-minute infusion of the δ-opioid receptor agonist d -Ala2- d -Leu5-enkephalin (DADLE; 200 μmol/L). In group 4, the protocol was similar to group 3 except that infusion of DADLE was preceded by infusion of the K ATP blocker glibenclamide (50 μmol/L). The salutary effects of both forms of preconditioning were primarily manifest as a better preservation of diastolic function, a reduced myocardial edema, and reduced creatine kinase leakage. This protection was abolished by administration of glibenclamide before DADLE. Conclusions —These data suggest that activation of δ-opioid receptors improves recovery of cold-stored hearts to a similar extent as ischemic preconditioning, most likely through an opening of K ATP channels. This provides a rationale for improving the preservation of hearts for transplantation by pharmacologically duplicating the common pathway to natural hibernation and preconditioning.
Misleading Statements and Illustrations in School Physiologies, Physics, and in Text-Books on Diseases of the Eye.
Authors: F. G. Murphy
Journal: JAMA (1899)

Kansas City, July 21, 1899. <h3>To the Editor:</h3> —If parallel rays of light focus on the retina and the image is inverted, why is the image not reinverted in myopia where the rays cross before they reach the retina; does the image of objects focus at a point as it seems to do in Figure I; and if the crystalline lens brings rays of light to a focus on the retina where would they focus if the lens were removed, and would the image be inverted? These are the questions students ask after seeing the statements and illustrations in the various text-books. Most text-books contain an illustration correctly showing the manner in which rays of light reach the retina, and many that are incorrect. As far as I know Figures 1, 2, 3 and 4 are the ones used the world over to illustrate errors of refraction, and they are
ABC of allergies: Allergy and the skin. I---Urticaria
Authors: M. W Greaves, R. A Sabroe
Journal: BMJ (1998)

Episodes of acute urticaria are common. Causes include type 1 hypersensitivity reactions to certain foods and drugs, including blood products. In up to 50% of cases a cause is not identified. The involvement of a particular food allergen can be confirmed by the radioallergosorbent test (RAST) and skin prick tests. Allergy to latex usually manifests as contact urticaria or with systemic symptoms but rarely presents with generalised urticaria. As with suspected reactions to peanuts it is recommended that tests for latex allergy be done in a hospital setting as severe systemic reactions may occur. Management of acute urticaria includes avoidance of the causative agent and treatment with H1 antihistamines. A short course of prednisolone can be given for severe episodes of urticaria unresponsive to antihistamines.

#### Causes of acute urticaria

Chronic urticaria is conventionally defined as the occurrence of daily or almost daily widespread itchy weals for at least six weeks. It occurs in at least 0.1% of the population and is much more troublesome than acute urticaria. Recent studies using an internationally recognised quality of life questionnaire, the Nottingham health profile, have highlighted the serious disability of patients with chronic urticaria, including loss of sleep and energy, social isolation, altered emotional reactions, and difficulties in aspects of daily living. The disability is of the same order as that experienced by patients with severe chronic ischaemic heart disease.



Dermographism induced with a calibrated, spring loaded dermographometer



### Physical urticarias

The first step is to identify patients with physical urticarias. These are patients in whom wealing and itching is provoked at the sites …
Clinical significance of IgG subclass antibodies to wheat flour antigens in bakers
Authors: U. Tiikkainen, M. Klockers
Journal: Allergy (1990)

We measured the IgG subclass antibody levels to wheat flour in 42 bakers and 20 controls with an enzyme immunoassay. The levels of total IgG, IgG1 IgG2 and IgG4 antibodies were significantly higher in the bakers than in the unexposed controls. The presence of anti‐wheat flour IgG subclass antibodies in the bakers was correlated with various clinical variables including IgE levels, duration of asthmatic or rhinitis symptoms, skin prick test response, peripheral blood eosinophil levels, bronchial histamine reactivity and responses to nasal challenge with wheat flour. The IgG subclass antibody levels of the total cohort of bakers did not correlate with any of the measured clinical variables. However, among men specific IgG4 and IgG1 antibody levels correlated negatively with total IgF levels and duration of rhinitis, respectively. We conclude that IgG and IgG subclass levels to wheat flour in bakers reflect exposure, but that it is not related to any specific clinical situation. The exact pathogenetic role of these antibodies in the development of occupational asthma and rhinitis is thus not clear.
Transmural cellular damage and blood flow distribution in early ischemia in pig hearts.
Authors: H Fujiwara, M Ashraf, S Sato, R W Millard
Journal: Circulation Research (1982)

Transmural histological changes were determined morphometrically in the left ventricular free wall of 20 pigs after ligation of distal left anterior descending coronary artery for 10, 20, 40, and 120 minutes. Hemodynamics were recorded and regional blood flow distribution was measured in the ischemic zone. Coronary occlusion produced regional transmural ischemia without producing significant systemic hemodynamic change. The microsphere blood flow technique revealed that blood flow was less than 0.05 ml/min per g in all layers of the ischemic zone, i.e., inner, middle, and outer thirds. Ischemic cellular damage was classified and quantified from grade 0 to grade 5 (0 being normal and 5 being the most severe damage) with light microscopy and confirmed by electron microscopy. Layers of 200 micrometers immediately beneath the endocardium and epicardium showed minimal ischemic damage of less than grade 1.4 regardless of duration of ischemia in all hearts. In the ischemic left ventricular wall, except for the above layers, a definite transmural gradient of the cellular damage existed from the inner third (grade 2.3 +/- 0.1) to the outer third (grade 1.3 +/- 0.2) at 20 minutes of ischemia and at 40 minutes of ischemia (grades 3.6 +/- 0.1 and 1.9 +/- 0.3, respectively). The transmural ischemic damage gradient disappeared at 120 minutes of ischemia, where the inner and outer third ischemic grades were both 5.0 +/- 0.1. The data suggest that the limited ischemic damage which occurs in the few cell layers beneath endocardium and epicardium may be explained by regional collateral blood flow. An early ischemic damage wavefront phenomenon does exist in the pig myocardium and is independent of myocardial blood flow and its distribution. The transmural cell damage gradient may be the result of transmural gradients of wall stress and intramyocardial pressure in vivo. Therefore, it appears that factors other than blood flow are the major determinants of ischemic cellular damage in the left ventricular wall of hearts lacking a collateral blood supply.
Diagnosis in Chronic Industrial Poisoning
Authors: Niels C. Klendshoj
Journal: JAMA (1962)

Increasingly, physicians are encountering difficulties in differentiating between impairment of health due to insidious exposure to chemicals and disease caused by other etiological factors. This situation is emphasized by the vast number of new chemicals being introduced every year into industry and everyday life. It has been our experience that painstaking scrutiny of all available data can materially increase diagnostic accuracy in such cases. We have applied principles of critical interpretation of laboratory data and physical findings. Even more so, we have analyzed the importance of accurate determination by the physician of the factual environmental exposure, not only in quantitative terms of the alleged offender, but also in respect to concomitant exposure both on and off the job.
Putting the neo into neoangiogenesis
Authors: Malcolm A.S. Moore
Journal: Journal of Clinical Investigation (2002)

Angiogenesis is the process by which new blood vessels develop by sprouting of preexisting vessels, and until recently this was considered the sole mechanism of blood vessel formation in postnatal life.The development of the vascular system in the embryo, termed vasculogenesis, is due to in situ differentiation of endothelial progenitors or angioblasts.Studies over the last five years have modified this dogma, since endothelial stem cells have been identified in the adult and have been shown to participate in new blood vessel formation in normal and pathological states, including tumor "neoangiogenesis" (1-5).
"PLASTIC REPAIR OF INGUINAL HERNIA"
Authors: P. G. Skillern
Journal: JAMA (1931)

To the Editor:  —The Journalfor Nov. 15, 1930, contains an article by Joseph A. Pettit, M.D., Portland, Ore., in which the author states: About the time this technic was brought out Skillern presented a plastic flap technic lacking in the essential advantages presented by mine. And on the next page Pettit writes further: I find three distinct disadvantages in the Skillern operation, in which the lower or lateral flap is plicated beneath the upper or medial flap: (1) It is not possible to make so extensive a plication; (2) it is not possible to construct a new fascial canal for the structures of the cord without producing an additional curve having a sharp and disadvantageous angulation, and (3) the general reconstruction is anatomically incorrect.  The article describing the operation referred to was published in 1922 (Skillern, P. G.: The Choice of Operation in Inguinal Hernia, Surg. Gynec. Obst
Medicine Is Not a Business
Authors: Charles D. Aring
Journal: JAMA (1974)

THE British National Health Service has completed its first quarter of a century. Meanwhile, we have been contemplating the kind of medical care deserved by the American citizenry. A decade ago, toward the end of his life, President Kennedy was urging Congress that we can no longer ask people to live in fear of a serious illness for which adequate funds were not available, and that man has the right of dignity in sickness as well as in health. Sickness is demeaning enough as it is. To practice an otherwise adequate kind of medicine limited by what the patient can afford is to adjust to a method of the market, and as is well known, the very character of business is out of harmony with the spirit of the profession. Getting the cost element out of the way of practice is meliorating and lends equanimity. In human relationships, it is
Continuous measurement of left ventricular volume using a single dimensional transducer: a comparison of two techniques in open chested dogs
Authors: G. J. WILSON, D. H. BERGEL
Journal: Cardiovascular Research (1975)

A comparison has been made of the continuous measurement of left ventricular volume in open chested dogs by two simple dimensional transducer systems: a mercury in-rubber strain gauge measuring epicardial arc length at the ventricular equator and a pair of electromagnetically coupled coils placed on opposite sides of the left ventricle to measure its diameter. The single dimensional measurements were converted to volume measurements after death by filling an intraventricular balloon with known volumes of liquid. The strain gauge proved clearly superior to the coupled coils because it was not possible in practice to position the coils precisely facing each other and they did not remain tangential to the epicardial surface throughout the cardiac cycle. A single epicardial strain gauge can provide sufficiently accurate measurements of left ventricular volume to warrant its use in physiological studies of cardiac function. Althongh considerable attention to detail is required this technique has the advantages of being inexpensive and producing a continuous record which is easily interpreted.
Seminoma and Epididymal Cysts in a Young Man With Known Diethylstilbestrol Exposure In Utero
Authors: Gene R. Conley
Journal: JAMA (1983)

EXPOSURE of women to diethylstilbestrol in utero has been linked to the development of adenosis and clear cell adenocarcinoma of the vagina.<sup>1,2</sup>A variety of male genital tract abnormalities, including epididymal cysts, maldescended testes, hypoplastic testes, varicoceles, and spermatozoal defects, occur with increased incidence in men exposed to diethylstilbestrol in utero.<sup>3,4</sup>Testicular tumors occur in adult mice given diethylstilbestrol,<sup>5</sup>and preneoplastic testicular changes have been described in mice exposed prenatally to diethylstilbestrol.<sup>6</sup>The possibility of carcinogenesis has been suggested in diethylstilbestrol-exposed males,<sup>3,4</sup>but, to our knowledge, until now no case of testicular cancer has been documented in a person exposed in utero to diethylstilbestrol. We report a seminoma and ipsilateral epididymal cysts in a 28-year-old man with known diethylstilbestrol exposure. <h3>Report of a Case</h3> A 28-year-old man was first seen with a large, painless scrotal mass that had slowly developed during one year. Antenatally, his
The potential of laminin-2-biomimetic short peptide to promote cell adhesion, spreading and migration by inducing membrane recruitment and phosphorylation of PKCδ
Authors: Sung Youn Jung, Jin-Man Kim, Seung-Ki Min, O. Bok Kim, Da Hyun Jang, Hyun Ki Kang, Byung-Moo Min
Journal: Biomaterials (2012)
THE CONTAGIOUSNESS OF LEPROSY
Authors: J. W. Lindsay
Journal: BMJ (1912)

A JOBN I it diminished 1ill, on the tenth day, no cough followed the in ection./0/ A A -AAt A, Injection of CHL, gr.j.B, Injection of CHLh, gr.iss.Par-i pasua with these changes there was a progressive sense of betterment anid return to health.He felt less exhausted after the couigh and his appetite improved.As I have said, the application of this treatment, even by the most dextrous, is quite impossible in children.Their veins, as a rule, are too sniall, even for the finest needles made, and are frequently buried in fat.Besides, very few young children could be coaxed into submitting to the daily prick of a needle, after having a lhandkerchief tourniquet applied to the arm, or hold the arimi steady enougli even if they would.During the past niine.y-ars,since I first published tllis method for treatiua pulmonary tubercle, I lhave lheard indirectly of alarming symptoms being attributed to the intravenous injection of iodoform.It is rather extra- ordinary that I slhould have practised it without inter- mission for nearly twelve years, and in that time given thousand of injections and neve'r once met with anything
Alternating Hepatic Intra-Arterial Floxuridine and Fluorouracil: A Less Toxic Regimen for Treatment of Liver Metastases From Colorectal Cancer
Authors: R. J. Stagg, A. P. Venook, J. L. Chase, B. J. Lewis, R. S. Warren, M. Roh, S. J. Mulvihill, B. J. Grobman, A. A. Rayner, D. C. Hohn
Journal: JNCI Journal of the National Cancer Institute (1991)

Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver. However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity. Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects. In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects. Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days. Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable. Of the 64 patients, 30 (47%) previously had received chemotherapy. Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months. In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity. Alternating HIA FUDRb and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination. [J Natl Cancer Inst 83:423–428, 1991]
Morphological and biochemical characterization of a human liver in a uPA-SCID mouse chimera
Authors: Philip Meuleman, Louis Libbrecht, Rita De Vos, Bernard de Hemptinne, Kris Gevaert, Joël Vandekerckhove, Tania Roskams, Geert Leroux‐Roels
Journal: Hepatology (2005)

A small animal model harboring a functional human liver cell xenograft would be a useful tool to study human liver cell biology, drug metabolism, and infections with hepatotropic viruses. Here we describe the repopulation, organization, and function of human hepatocytes in a mouse recipient and the infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) of the transplanted cells. Homozygous urokinase plasminogen activator (uPA)-SCID mice underwent transplantation with primary human hepatocytes, and at different times animals were bled and sacrificed to analyze plasma and liver tissue, respectively. The plasma of mice that were successfully transplanted contained albumin and an additional 21 human proteins. Liver histology showed progressive and massive replacement of diseased mouse tissue by human hepatocytes. These cells were accumulating glycogen but appeared otherwise normal and showed no signs of damage or death. They formed functional bile canaliculi that connected to mouse canaliculi. Besides mature hepatocytes, human hepatic progenitor cells that were differentiating into mature hepatocytes could be identified within liver parenchyma. Infection of chimeric mice with HBV or HCV resulted in an active infection that did not alter the liver function and architecture. Electron microscopy showed the presence of viral and subviral structures in HBV infected hepatocytes. In conclusion, human hepatocytes repopulate the uPA+/+-SCID mouse liver in a very organized fashion with preservation of normal cell function. The presence of human hepatic progenitor cells in these chimeric animals necessitates a critical review of the observations and conclusions made in experiments with isolated "mature" hepatocytes. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;41:847–856.)