tbuckley/cabot-search huggingface dataset:
Abstract 1935: Potent anti-tumor effects of TIC10 require Foxo3a and TRAIL gene upregulation
Authors: Joshua E. Allen, Gabriel Krigsfeld, Akshal S. Patel, Gen Sheng Wu, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2012)

Abstract TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is an endogenous protein that induces tumor-selective apoptosis and is currently being tested in clinical trials as an anti-tumor agent. Despite promising preclinical activity, recombinant human TRAIL suffers from efficacy-limiting properties such as short serum half-life, stability, cost, and limitations in delivery, e.g. to the central nervous system. We hypothesized that induction of the human TRAIL gene by small molecules may overcome these limitations of TRAIL-based protein therapy. A cell-based luciferase reporter screen using the human TRAIL promoter identified TIC10 as a p53-independent small molecule inducer of the TRAIL gene. TIC10 induces TRAIL on the surface of normal and tumor cells, in sera of non-tumor-bearing mice, and throughout the tumor microenvironment. Co-culture experiments suggest that TRAIL upregulation by normal cells can contribute to the anti-tumor response of TIC10 through a TRAIL-mediated bystander effect. TIC10-induced TRAIL causes tumor-specific and TRAIL-mediated cell death as indicated by inhibition of cytotoxic effects following TRAIL gene knockdown in vitro and in vivo. Expression profiling of TIC10-induced transcriptional changes revealed altered expression levels of Foxo3a target genes, including DR5. We found that TIC10 causes the nuclear translocation of Foxo3a, but not Foxo1, to upregulate TRAIL gene transcription as determined by chromatin-immunoprecipitation assays. Western blot analysis indicated that TIC10 potently inhibits the phosphorylation of Foxo3a at Ser253 and Ser294 that normally docks the transcription factor to 14-3-3 proteins in the cytosol. Dual inhibition of Akt and ERK by TIC10, by other individual small molecule kinase inhibitors in combination or targeted siRNA inhibited the phosphorylation of these critical serine residues and synergistically induced Foxo3a-dependent TRAIL and TRAIL-mediated cell death. TIC10 is a promising first-in-class anti-tumor agent with a broad range of anti-tumor effects in preclinical animal models including othrotopic GBM, immunocompetent lymphoma, xenografted colon, lung, or breast cancers, and exhibits synergy with taxanes as well as bevacizumab among other agents. TIC10 appears to have no measurable toxic effects in mice including evaluation of serum chemistries, liver function studies, LDH, tissue histology, weight of the animals or behavioral changes. We are pursuing the clinical translation of these important findings that indicate a favorable and wide therapeutic index for a novel anti-tumor agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1935. doi:1538-7445.AM2012-1935
JAMA Online—New Features, New Functions
Authors: Margaret A. Winker
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE PRODUCTION OF METHEMOGLOBIN BY PNEUMOCOCCI
Authors: Rufus Cole
Journal: The Journal of Experimental Medicine (1914)

1. Pneumococci in contact with hemoglobin transform this into methemoglobin. This reaction occurs only when the pneumococci are living; it is not induced by the culture fluid or by extracts of the bacteria. 2. The reaction does not occur when hemoglobin is added to an emulsion of washed pneumococci in salt solution. However, if minute traces of dextrose be added to such a mixture, the reaction quickly occurs. The dextrose may be replaced by any one of a number of other sugars, and also by certain other organic substances, if the latter are added in large amounts. Certain other organic substances are not able to replace dextrose, but it has been impossible to determine any special molecular configuration on which this property depends. 3. The formation of methemoglobin by pneumococci probably resembles the formation of methemoglobin by certain chemical substances, such as aminophenol. 4. From the work of others it is probable that the formation of methemoglobin is always a reaction of oxidation. In the formation of methemoglobin by reducing agents, the latter are first oxidized, this occurring better in the presence of oxyhemoglobin. In certain instances an alternate oxidative and reduction of the transforming agent occurs, so that the reaction is continuous. The effect which the presence or absence of free oxygen has on the reaction with pneumococci suggests that this follows similar lines. 5. The reaction does not occur in the absence of oxygen. If the free oxygen be first removed, and then replaced, the reaction occurs more rapidly than if the oxygen had not been removed. The presence of free oxygen in excess slightly delays the reaction, possibly because of the inhibition of the reduction process which forms the first part of the reaction. 6. The explanation of this phenomenon of methemoglobin production is not only of importance so far as this special reaction is concerned, but also because it suggests an explanation for the manner in which pathological effects are produced by those bacteria which apparently produce no soluble toxin.
Involvement of immunoglobulin E in the secretory processes of alveolar macrophages from asthmatic patients.
Authors: M Joseph, A B Tonnel, G Torpier, A Capron, B Arnoux, J Benveniste
Journal: Journal of Clinical Investigation (1983)

Alveolar macrophages from nonatopic donors were passively sensitized with allergen-specific IgE antibody from the serum of asthmatic patients. A selective release of 4-8% of the lysosomal beta-glucuronidase of these cells occurred within 30 min of contact with the related allergen or with anti-human IgE antibody, in the absence of any mast or basophil cells. The cell reactivity was dependent on the interaction of macrophages with IgE, as shown by the disappearance of the allergen-induced enzyme release after heating or IgE-immune adsorption of the sensitizing serum, but not after IgG-adsorption. Alveolar macrophages from asthmatic patients behaved similarly to passively sensitized normal macrophages. Contact with the related allergen or with anti-IgE antibody induced the same percentage of enzyme release, demonstrating that these cells possess allergen-specific IgE bound on their surface. 18% of them formed rosettes with anti-IgE-coated sheep erythrocytes, and 15-22% with allergen-coated erythrocytes, but lost this property after preincubation with the specific allergen. The presence of IgE-specific receptors on the macrophage surface was demonstrated both at the ultrastructural level with immunoperoxidase labeling, and at low magnification by the formation of 15-18% rosettes with human IgE-coated erythrocytes. The formation of such rosettes was inhibited after incubation of alveolar phagocytes with aggregated myeloma IgE. On the basis of these observations, the participation of the alveolar macrophages in IgE-mediated pulmonary hypersensitivity must be considered. Its precise involvement requires, however, further investigations.
The Economics of Generic Prescribing: Winners and Losers
Authors: Louis Lasagna
Journal: JAMA (1986)

In 1980 an evaluation of the price of prescription drugs in the wake of the passage of a generic substitution law in New York State concluded that while generic drugs were on average somewhat less costly than brand name drugs, prices (even for the same drug written the same way) varied enormously and unpredictably among pharmacies, generic prescriptions occasionally cost more than branded ones, and "savings" from generic substitution were often not passed on to consumers, in contravention of the statute.<sup>1</sup> In this issue ofTHE JOURNAL, Bloom et al<sup>2</sup>examine these and other issues in a much broader and more definitive study. Because their research involves 39 states and almost 900 000 prescriptions and 1400 pharmacies, and because of the scope of their analyses, this article is a landmark. Despite some expressions of concern about the quality of multisource drugs or the appropriate use of pharmacists' training,
Dermatology and the human gene map
Authors: CELIA MOSS
Journal: British Journal of Dermatology (1991)

Summary Chromosomal localization has been established for many genetic traints. Gene mapping may lead to the identification of disease genes, an understanding of pathogenesis, and the development of rational therapy, as well as facilitating antenatal diagnosis and genetic counselling. ‘The new genetics’1 is therefore of great interest to the clinician. Unfortunately the complex technology and unfamiliar vocabulary of molecular biology often deter non-specialists from keeping abreast of these developments. This account explains the principles of gene mapping, discusses its relevance to dermatologists, and lists the established loci of dermatologically important genes.
The Effect of Hyperventilation on Various Arrhythmias
Authors: D. SCHERF, M. GOLDFARB, R. BUSSAN
Journal: Circulation (1955)

The influence of hyperventilation on various cardiac arrhythmias is examined. Auricular and ventricular extrasystoles disappear temporarily, paroxysmal auricular and ventricular tachycardias aswell as attacks of short paroxysmal auricular fibrillation are abolished by hyperventilation. An attempt is made to explain these phenomena.
DELAYED HYPERSENSITIVITY IN THE DEVELOPMENT OF CIRCULATING ANTIBODY. THE EFFECT OF X-IRRADIATION
Authors: S. B. Salvin, Robert F. Smith
Journal: The Journal of Experimental Medicine (1959)

The induction of delayed type of hypersensitivity to diphtheria toxoid in the guinea pig was not inhibited by total body irradiation up to 300 r in intensity. X-ray doses of 200 to 300 r administered about 18 hours before sensitization caused the period of delayed hypersensitivity to be extended to the 19th to 21st day postsensitization in. the absence of circulating antibody. X-ray doses of 50 to 100 r caused a decrease in the titer of circulating antibody, although delayed hypersensitivity lasted for a normal time. When 300 r irradiation was administered 18 hours after sensitization, delayed hypersensitivity lasted for the usual period and circulating antibody first appeared at the usual 13 to 14 days after sensitization. Introduction of normal serum or leucocytes into irradiated animals apparently did not reduce damage to the mechanism regulating the rate of antibody synthesis.
Psychological Mediation of a Type of Oxidative DNA Damage, 8-Hydroxydeoxyguanosine, in Peripheral Blood Leukocytes of Non-Smoking and Non-Drinking Workers
Authors: Masahiro Irie, Shinya Asami, Shoji Nagata, Masakazu Miyata, Hiroshi Kasai
Journal: Psychotherapy and Psychosomatics (2002)

&lt;i&gt;Background:&lt;/i&gt; The present study investigates whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA damage relevant to carcinogenicity, can be associated with psychological factors, in order to clarify the possible stress-cancer linkage from a genetic viewpoint. &lt;i&gt;Methods:&lt;/i&gt; We performed a cross-sectional study in which we examined the relationships of the levels of 8-OH-dG in peripheral blood leukocytes to various psychological factors, including the Profile of Mood States (POMS) and the Center for Epidemiologic Studies Depression Scale (CES-D) in 38 non-smoking and non-drinking workers (19 males and 19 females). &lt;i&gt;Results:&lt;/i&gt; The levels of 8-OH-dG in male subjects were negatively correlated with the Tension-Anxiety scores of the POMS. In contrast, the levels of 8-OH-dG in female subjects were positively correlated with the Depression-Rejection scores of the POMS and the CES-D scores, and negatively associated with the Vigor scores of the POMS, respectively. Male subjects who had self-blame coping strategy displayed significantly high levels of 8-OH-dG. Moreover, the worse the subjective closeness to parents in childhood, the higher the levels of 8-OH-dG became in male subjects. The levels of 8-OH-dG increased reliably in subjects who had experienced the loss of a close family member within 3 years, when compared with non-bereaved subjects. &lt;i&gt;Conclusions:&lt;/i&gt; Psychological distress may be associated with cancer risk, although sex difference influences them. Inadequate coping styles, possibly resulting from a poor interpersonal relationship with parents since childhood, and experience of a relatively recent loss of a close family member also appear to influence the pathogenesis of cancer.
Lactic Dehydrogenase Activity in Acute Myocardial Infarction
Authors: J. King, A. P. B. Waind
Journal: BMJ (1960)

TIBRrSl 1361Mr. Westwood's subjects (Cases 14-22), who were not under psychiatric treatment.Thus, of the psychiatric group 11 out of 13 had sperm counts of 50 millions per ml.or more, while of the non-psychiatric group only two out of nine had counts over this level.There was little difference in volume, percentage of abnormal forms, or motility between the two groups, but differ- ences in sperm density were reflected in an overall rating of " highly fertile " or " fertile " in 10 out of 13 psychiatric as against 2 out of 9 non-psychiatric cases.Confirmation (from larger and more comprehensive surveys) of the striking difference in fertility between the two subgroups in our series would be of considerable importance in relation to theories of aetiology of homo- sexuality.Hypotheses readily come to mind in this context, but we think it inappropriate to list them at this stage in view of the small size of our study.The difference noted, if not fortuitous, may well be an arti- fact of the selection procedure.For example, some of the non-psychiatric subjects may have volunteered because they were already conscious or suspicious of genital abnormality, whereas psychiatric patients who chose to take part may have been influenced by quite different motives.Summary 22 men who were predominantly or exclusively homo- sexual in orientation provided seminal specimens for analysis.Of the 22, 8 were rated highly fertile, 4 fertile, 5 borderline, 3 subfertile, and 2 sterile, on the basis of the seminological findings.The clinical diagnosis of " constitutional type " homo- sexuality was compatible with a high degree of fertility as judged seminologically.
Vincent Van Gogh And Glaucoma
Authors: Keith Spencer Felton
Journal: JAMA (1971)

<h3>To the Editor.—</h3> With respect to the conditions leading to "Night Cafe," and the halos about the lamps, A.M. Hammacher, in his stunning pictorial text,<i>Genius and Disaster: The Ten Creative Years of Vincent Van Gogh</i>(New York, Harry N. Abrams Inc, 1968) says it succinctly: In the summer of 1888, another sign of the increased formative power of Vincent's observation under the force of inner tension was the new vigor of his drawing. His hand had never been so firm, nor his sight so clear; it was as if the birth of the world and all its objects were taking place again through his creative energy. The symbol is then the circle. This was barely two years before his suicide; "Night Cafe" was painted in September 1888. If there is sufficient evidence to substantiate visual affliction in the Dutchman, let it come forth. Otherwise, to use ophthalmologic symptoms to
MECHANICAL ASPECTS AND SURGICAL MANAGEMENT OF STERILITY IN MEN
Authors: Vincent J. O'Conor
Journal: JAMA (1953)

A study of 123 patients who had complete azoospermia and in whom either exploration of the scrotal content or corrective sugery was performed is reported. Azoospermia was caused by a variety of factors (incomplete or improper development of the ductal system, obstruction in the epididymis or in the vas as a result of postinflammatory constriction, occlusion of the lumen or the ejaculatory ducts, and inadvertent or purposeful division of the vasa). Operation to relieve vasoepididymal obstruction is indicated only the presence of a normally functioning testicle. There are 4 types of operations for the correction of sterility. If these operations are unsuccessful it is possible to bring the free and cut ends of the vas into the midline of the scrotum and then allow them to empty continuously into and inverted skin pouch to create a reservoir of sperm for artificial insemination. In this series there were 61 patients in whom there was sufficiently hopeful indication for success to warrent bilateral or unilateral epididymovas anastomosis. In only 23 of these could it be said that there was complete success. Only 5 of these men were able to effect pregnancy. Reanastomosis of the vas after prior voluntary sterilization resulted in a 70% success rate for surgery.
Coronary heart disease in the aged.
Authors: A. K. Thould
Journal: BMJ (1965)

ment was required and no case progressed to local abscess formation.(c) Blockage Alone.-Thisoccurred without evidence of inflammation in only 12 cases (2 %).Usually there was evidence that the tip of the catheter had pierced the vein wall, causing extravasation.In order to facilitate introduction of the polythene cannula into the tiny veins of the infant, the tip of the cannula is often trimmed obliquely by the surgeon, and is probably the main reason for this accident.A " sharp-pointed" cannula should therefore be rounded off before introduction.(d) Deep Venous Thrombosis.-Generalized oedema of the oannulated limb occurred in one case only on the fourth day, and the infusion was stopped.There was only slight redness of the infused vein, and no absolute conclusions can be drawn.The infant was 5 days old, was not given anticoagulants, and recovered uneventfully.(e) P Septicaemia.-Onefour-month-old infant developed septicaemia during the forty-eight hours following a difficult reduction of an ileocolic intussusception.Intravenous fluids were given during this time and were discontinued after 36 hours.There was no obvious thrombophlebitis.Acute osteitis of two long bones ensued, and an abscess developed in the laparotomy wound.A penicillin-resistant strain of Staphylococcus aureus was cultured in the pus of all three septic foci; with appropriate treatment the infant made a full recovery.The most probable source of infection was the wound itself, during operation, but the possibility that the organism was introduced via the infusion apparatus, although unlikely, cannot be ruled out. ConclusionThe Heller valve provides a simple, cheap, reliable, and accurate method of giving intravenous fluids to newborn infants.Its use reduces the time spent by the medical and nursing staff in supervising intravenous drips in neonates ; and it can readily be adapted for other purposes.Minor complications occur, as with any form of intravenous infusion in infants, but their incidence is not high, and is probably much lower than that associated with earlier tech- niques.In a series of 500 valve-infusions only two major com- plications were found which might be attributed to this method.The valve costs 6s.9d., which is little more than the cost of a single disposable drip set, and it may be used more than fifty times before leak-back occurs. SummaryA method of administering intravenous fluids to infants is described and assessed in the light of experience of over 1,200 infusions.The advantages over more conventional methods are discussed and the possibilities of the adaptation of the system for other purposes are indicated.The Heller valve is manufactured by Medical and Industrial Equipment Ltd., 10/12 New Cavendish Street, London, to whom I am grateful for information and advice.I am also indebted to Mr. J.
The Night Side: Chronic Fatigue Syndrome and the Illness Experience
Authors: Michael Loudon
Journal: JAMA (1997)

Floyd Skloot, poet and public policy analyst, fell ill on December 7, 1988.<i>The Night Side</i>describes his illness experience. Let's sketch out his story, as he describes it. Aged 41 years, a lean, fit, and busy man, Skloot wakes up in a Washington, DC, hotel feeling ill, "too exhausted to fold back the sheets." He does not recover. Through early 1989 he and his wife visit half a dozen doctors. A Dr Mudgett suggests to Skloot that his postviral fatigue may be complicated by "psychological overlay." Skloot is not amused. It takes 5 months before he is correctly diagnosed with chronic fatigue syndrome (CFS). But finally he meets a doctor who understands his illness, who is an exception to the rule that most doctors and researchers have "virtually ignored" CFS. While other CFS sufferers belong to a "vast subpopulation of Americans who feel betrayed by the medical community," Skloot is
Bush makes controversial appointment of new head of family planning office
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

In a controversial move President George Bush has appointed Susan Orr as acting deputy assistant secretary for population affairs, to head the Office of Population Affairs at the Department of Health and Human Services.

Dr Orr, who is not a physician but has a PhD, was widely criticised in the US press because in a 2001 interview with the Washington Post she was quoted as saying that she supported a Bush proposal to stop requiring health plans for federal employees to cover contraception. She was quoted as saying, “We're quite pleased, because fertility is not a disease.”

Dr Orr has served in the US health department for six years. She was working at the conservative Family Research Council—whose slogan is “family, faith, and freedom”—when …
A FAMILIAL CASE OF ACNE VULGARIS WITH LESIONS SUGGESTING A RELATIONSHIP TO ACNE CONGLOBATA.
Authors: F. F. HELLIER
Journal: British Journal of Dermatology (1939)

Journal Article A FAMILIAL CASE OF ACNE VULGARIS WITH LESIONS SUGGESTING A RELATIONSHIP TO ACNE CONGLOBATA. Get access F. F. HELLIER, M.A., M.D., M.R.C.P. F. F. HELLIER, M.A., M.D., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 51, Issue 3, 1 March 1939, Pages 109–119, https://doi.org/10.1111/j.1365-2133.1939.tb10658.x Published: 01 March 1939