tbuckley/cabot-search huggingface dataset:
Abstract 2259: Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for krüppel-like factor 4
Authors: Changchang Liu, Stephen La Rosa, Engda Hagos
Journal: Cancer Research (2014)

Abstract Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) in their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which can result in cancer formation. One protective response to increased levels of ROS is the induction of cellular senescence. Recently, we found that mouse embryonic fibroblasts (MEFs) null for Klf4 are genetically unstable, as evidenced by the presence of DNA DSBs. However, it is yet unknown whether KLF4 is involved in regulating oxidative stress-induced DNA damage. Therefore, we sought to determine the mechanisms by which ROS induce genomic instability in Klf4-deficient MEFs. With SA-β-Gal staining, we show that Klf4-/- MEFs enter senescence earlier than Klf4+/+ MEFs, and western blot shows accumulation of p21 and p53 with increasing passages. In addition, immunostaining against γ-H2AX indicates that the increased level of DNA damage in Klf4-/- MEFs positively correlates with ROS accumulation. Consistent with ROS as a source of DSB in Klf4-/- MEFs, treatment with NAC, reduced the accumulation of DNA damage. Our RT-PCR result demonstrates that Klf4-/- MEFs have decreased expression of the antioxidant gene, Gstα4. The downregulation of the Gstα4 correlates with significant levels of ROS accumulation, as shown by DCFDA and FACS analysis, and thus the oxidative stress-induced premature senescence. Together these findings suggest a mechanism by which KLF4 protects against DNA damage and oxidative stress at least in part through the regulation of Gsta4 and likely related genes. Note: This abstract was not presented at the meeting. Citation Format: Changchang Liu, Stephen La Rosa, Engda Hagos. Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for krüppel-like factor 4. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2259. doi:10.1158/1538-7445.AM2014-2259
Phase II Trial with Gemcitabine, Paclitaxel and Bevacizumab for the First Line Treatment of Metastatic Breast Cancer.
Authors: A. Guardino, M. Chen, M. Levy, C. Chen
Journal: Cancer Research (2009)

Abstract Background: Both gemcitabine and paclitaxel in combination, and paclitaxel and bevacizumab in combination, have shown higher response rates and improved time to progression (TTP) over single agent paclitaxel for the first line treatment of metastatic breast cancer. This phase II study was initiated to evaluate the efficacy and tolerability of combination gemcitabine, paclitaxel and bevacizumab as first line treatment for HER2 negative metastatic breast cancer.Methods: Women with HER2 negative metastatic breast cancer who have not received prior chemotherapy for metastatic disease are eligible for the study. The primary end point is time to progression (TTP). Secondary endpoints include duration of response, objective response rate and toxicities. Patients receive gemcitabine 1000 mg/m2 IV on days 1, 8, &amp; 15, paclitaxel 80 mg/m2 IV on days 1, 8, &amp; 15, and bevacizumab 10 mg/kg on days 1 &amp; 15, on an every four week cycle. Patients are evaluated with imaging studies including CT and bone scan at baseline and every 3 months. Response to treatment is evaluated using RECIST methods. Treatment continues until disease progression or unacceptable toxicities and at which point the drug thought to cause the toxicity will be discontinued.Results: As of January 2009, 21 patients with a median age of 54 years (range: 30-76) have been enrolled. Estrogen and progesterone receptor was positive in 16 and 10 patients, respectively and 4 patients were negative for both. Among 17 evaluable patients, the clinical benefit rate (CR+PR+SD ≥ 24 weeks) is 88%. 10 patients have reached the study endpoint with a median TTP of 12 months (mean TTP of 13.3 months). In addition, the combination treatment with bevacizumab has been well tolerated without clinically significant bleeding and with less than 10% of patients experiencing grade 3 peripheral neuropathy, grade 3 hypertension and less than 5% experiencing grade 3 proteinuria. 4 patients experienced a thrombotic event, of which 2 were catheter-related. The primary toxicities were hematological which were expected. 16 patients experienced grade 3/4 hematological toxicities and responded to dose reductions. 9 patients remain on treatment.Discussion: The addition of bevacizumab to combination chemotherapy with gemcitabine and paclitaxel is well tolerated for first line therapy of HER2 negative metastatic breast cancer. Clinical activity has been observed and phase II enrollment is ongoing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6089.
Evaluating the<i>Haemophilus influenzae</i>Type b Conjugate Vaccine PRP-D
Authors: John B. Robbins, Rachel Schneerson
Journal: New England Journal of Medicine (1990)

Landsteiner1 and then Avery and Goebel2 discovered how to increase the ability of saccharides (haptens) to elicit antibodies by chemically binding them to proteins to form conjugates. About three quarters of a century later, these discoveries have inspired the development of polysaccharide—protein conjugate vaccines. The first of this new generation of vaccines to have their effectiveness verified by clinical trials are Haemophilus influenzae type b conjugates.3 H. influenzae type b causes systemic infections, of which meningitis is the most frequent and poses the greatest threat. H. influenzae type b is transmitted by aerosol to the respiratory tracts of close contacts. . . .
Editors' Viewpoint—Response
Authors: Mario P. Colombo, George C. Prendergast
Journal: Cancer Research (2014)

Exciting clinical studies of antibody therapies that target so-called immune checkpoint molecules like CTLA4 and PD1 have re-fired longstanding hopes in cancer immunotherapy. Recently, PD1 blockade has shown unexpected efficacy in the setting of non–small cell lung cancer (NSCLC), and its study in
Child-Murder and Wet-Nursing
Authors: W. Acton
Journal: BMJ (1861)

<h3>Aim</h3> To evaluate the efficacy of the three-dimensional (3D) Strabismus Photo Analyzer for estimating binocular alignment using photographs. <h3>Methods</h3> Thirty-two subjects with exotropia, 30 subjects with esotropia and 38 orthotropic subjects were included. Two independent ophthalmologists examined the angle of deviation using the Krimsky test and prism and alternate cover test (PCT). Full-face photographs were obtained using an 8.2-megapixel digital single-lens reflex camera, and the images were analysed using the 3D Strabismus Photo Analyzer. The images were adjusted for age-dependent ophthalmic biometry and angle κ. The main outcome measures were inter-observer variability, test‐retest reliability and correlation between the angles of deviation measured by different methods. <h3>Results</h3> The 95% limit of agreement of inter-observer variability was ±3.5° (6.1 prism dioptres (PD)), ±3.1° (5.4 PD) and ±1.5° (2.6 PD) for the Krimsky test, PCT and the 3D Strabismus Photo Analyzer, respectively. The test‐retest reliability was ±2.8° (4.9 PD) for the 3D Strabismus Photo Analyzer versus the Krimsky test. The results of the Krimsky test and 3D Strabismus Photo Analyzer showed a strong positive correlation. <h3>Conclusions</h3> The 3D Strabismus Photo Analyzer is a simple and reliable tool for measuring ocular deviation. It has excellent agreement with the Krimsky test and substantially improved reproducibility.
"YEAST IN THE TREATMENT OF PELLAGRA"
Authors: N. M. Owensby
Journal: JAMA (1925)

<h3>To the Editor:</h3> —In an abstract with this title (The Journal, June 20, p. 1947), you emphasize Goldberger's work. It is indeed difficult to understand why you should regard Goldberger's efforts to evade the vitamin theory as to the causation of pellagra advanced by Funk as worthy of comment, and ignore efforts to substantiate Funk's theories. At first, Goldberger advanced the theory that the absence of amino-acids in diet was the causative factor. Since the publication of my article in theMedical Record, he has stated that the factor is one which he designates as P-P, which is derived from brewers' yeast and administered in tomato juice or milk. You are, of course, aware of the fact that brewers' yeast, milk and tomato juice furnish one of thre greatest sources for vitamin B. It is particularly significant that the protein diet heretofore recommended by Goldberger had to be abandoned
Cardiac Roentgenology: Plain Films and Angiocardiographic Findings
Authors: Joseph E. Whitley
Journal: JAMA (1970)

Dr. Meszaros undertook the mighty task of describing and illustrating in one volume the radiologic findings in acquired and congenital heart disease. How were so many diseases of the heart and great vessels covered in 586 pages? One of the stated aims of the book is to provide information about cardiac roentgenology to noncardiologic clinicians and radiologists on whom the subleties of electrocardiography, pressure curve analysis, etc, would probably be lost. Thus, the basic clinical, electrocardiographic, and hemodynamic data are only superficially covered in most disease states and deleted altogether in the more exotic. The plain film, fluoroscopic, and the angiographic findings are described and usually illustrated. The illustrations are somewhat uneven but adequate. The radiographs and their reproduction suffer by comparison with such older, less comprehensive classics as the 1959<i>Diagnosis of Congenital Heart Disease</i>by Kjellberg et al. The lists of references are good. There are some anachronisms.
Effect of Estrogens and Calcium Carbonate on Bone Loss in Postmenopausal Women
Authors: Robert R. Recker, Paul D. Saville, Robert P. Heaney
Journal: Annals of Internal Medicine (1977)

Sixty postmenopausal women were placed in three groups—control, sex hormone-treated, and CaCO3-treated—and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective.
An Unexpected Burden—The Safety of Air Ambulances
Authors: Alan R. Dimick
Journal: JAMA (1988)

<h3>To the Editor.</h3> —As members of the American Medical Association's (AMA) Commission on Emergency Medical Services, we wish to respond to the article entitled "An Unexpected Burden,"<sup>1</sup>which appeared recently inThe Journal's A PIECE OF MY MIND section. This thoughtful essay described a physician's decision to dispatch a hospital-based medical helicopter to transport a critically ill patient and the physician's reaction to the helicopter's subsequent crash, due apparently to flying in adverse weather conditions. The Commission on Emergency Medical Services, composed of 27 national emergency medical services organizations, advises the AMA Board of Trustees on matters relating to emergency medical care. In October 1986, the Board asked the Commission to conduct a study of air ambulance services in response to the alarmingly high accident rate. Commission members intimately familiar with aeromedical transport have completed this study, which will be presented to the AMA House of Delegates at
Absence of Carcinogenic Properties of Propranolol in Mice
Authors: M. J. Tucker, S. J. Alcock, S. B. de C. Baker
Journal: BMJ (1965)

Total faecal calcium is then given by f=(d+s) (1-a)+s' ................... (1) The discussion is simplified by taking s+s'=287 mg./day, the value found by Dr.Rose and his colleagues, and s'=40 mg./day, the value derived by Heaney.' Equation ( 1) then reduces to f=(d+247) (1-a)+40 or, a.d=(d-f)-247.a+287............ (2) Equation (2) is plotted for various values of a and d in the Figure.At constant a values a.d on (d-f) is a family of straight lines with gradient unity.The line degenerates to a point, V, at a = 0. XY and UT represent the lines for a=1 and a =0.5 At constant d values a.d on d -f is a family of straight lines radiating from V (a = 0).VW and VY represent the lines for diets of 300 and 1,01)0 mg./day and os values from 0 to 1.T
Psychopathic States and Attempted Suicide
Authors: I. R. C. Batchelor
Journal: BMJ (1954)

Blood urea 28 mg./100 ml.198 mg.!100 ml.196 mg./100 ml.CO2 combiing 48 1 ml.CO., 35 ml.CO. 21ml.CO,' power 100 ml. 100 ml. 100 ml.Plasma chlorides .. 109-4 mEq/litre 103 mEq/litre 117 mEq/litre Plasma sodium .. 142 Serum potassium.. 55 ,,
Emil Fischer (1852-1919) Organic Chemist
Authors: Harold P. Schedl
Journal: JAMA (1967)

To the Editor:—  The editorial on Emil Fischer ( 198 :313, 1966) is an interesting description of an amazing man. There is an error in the description of Veronal (p 314) as one of the first of the modern soporifics that preceded the barbiturates. Actually, Vernonal is a name that Fischer applied to barbital, or diethyl barbituric acid. The name diethylmalonyl urea is the original nomenclature for diethyl barbituric acid. There is a story that Fischer visited Verona and found it to be so sleepy a town that he chose the name for his best soporific.
Please do not resuscitate: Do we perform cardiopulmonary resuscitation on living or dead people?
Authors: John C Chambers
Journal: BMJ (2006)

EDITOR—Cardiopulmonary resuscitation (CPR) in the continuing care setting is controversial.1 Patients' rights are central to decision making on resuscitation in the NHS2 and independent sector,3 but it is unclear what these rights are.

Although the European Convention on Human Rights and Fundamental Freedoms4 formed the basis of the joint was never intended to help shape one's response to a cardiac arrest. In applying articles from …
Infective Endocarditis
Authors: Vincent Quagliarello
Journal: JAMA (2005)

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
NOTES ON SOME OF THE NEWER REMEDIES USED IN DISEASES OF THE SKIN.
Authors: L. DUNCAN BULKLEY
Journal: JAMA (1896)

This is certainly the age of progress, and the cry is continually for something new. The wonderful advances which have been made in medicine and surgery during the past fifty years would seem to warrant us in looking for newer remedies and measures in all departments of medicine; and indeed, the number of these which have of late years been pressed upon us by writers in medical journals and manufacturers, is so great that much confusion of thought and purpose is often induced thereby. It is well, therefore, now and again, to stop and weigh and try to estimate the value or worthlessness of the new, and to see what of it should be added to our stock of old, and thus to recognize where true advance has been made. It would be really amusing, were it not so sad, to read and record carefully all that is written in
HYPERSENSITIVITY TO PENICILLENIC ACID DERIVATIVES IN HUMAN BEINGS WITH PENICILLIN ALLERGY
Authors: Charles W. Parker, Jack Shapiro, Milton Kern, Herman N. Eisen
Journal: The Journal of Experimental Medicine (1962)

Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant.
Premedical Education and the Selection of Medical Students
Authors: Perry J. Culver
Journal: New England Journal of Medicine (1963)

GOOD health is one of the United States' greatest resources and is vital to its survival. The flood of medical writings in the popular press is evidence of individual interest and personal concern with well-being. Leaders of medicine, government, labor, industry and consumer groups are striving to discover formulas for providing the best possible medical care for all citizens consistent with the economy and with preservation of the amenities of the doctor–patient relation.It is obvious that the medical schools of the nation will have to educate many more highly qualified students each year to provide the research personnel, the . . .
The Role of LMO2 in Development and in T Cell Leukemia After Chromosomal Translocation or Retroviral Insertion
Authors: Chang-Hoon Nam, Terence H. Rabbitts
Journal: Molecular Therapy (2005)

Chromosomal translocations are primary events in the development of leukemias, representing at least one genetic feature of the putative cancer stem cell. Studies of genes influenced by chromosomal translocations have yielded a vast amount of information about how cancer is initiated and maintained. In particular, acute leukemias have demonstrated that chromosomal translocations often involve transcription regulators that function by interacting with proteins and by controlling cell fate in the aberrant setting of the developing cancer cell. As a quintessential chromosomal translocation gene product, LMO2 has many properties that typify this class of molecule. In addition to its involvement in chromosomal translocations, the LMO2 gene was inadvertently activated in an X-SCID gene therapy trial by retroviral insertion. New molecular therapies targeted directly at the LMO2 protein could have major impact as adjuncts to existing therapies or as therapeutics in their own right. In this review, we outline the current knowledge about LMO2 and some possible routes to develop reagents that might be possible macromolecular drugs in the future.
Does Elective Sclerotherapy Improve the Efficacy of Long–Term Propranolol for Prevention of Recurrent Bleeding in Patients With Severe Cirrhosis? A Prospective Multicenter, Randomized Trial
Authors: Olivier Ink, Thierry Martin, Thierry Poynard, Marc Reville, Marie-Laure Anciaux, Claude Lenoir, Jean-Luc Marill, Hélène Labadie, Claude Masliah, Daniel Perrin, Jean-Claude Chaput, Denis Vetter, Claude Eugene, Louis Lebodic, Henri Licht, Jean-Pierre Etienne
Journal: Hepatology (1992)

ABSTRACT We conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child–Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean ± S.D.) of recurrent bleeding at 2 yr were 42% ± 6% for propranolol plus sclerotherapy and 59% ± 6% for propranolol alone (a nonsignificant difference). Twentyeight patients from the propranolol group but only 12 patients from the propranolol–plus–sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p &lt; 0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 ± 7) than in the propranolol–plus–sclerotherapy group (5 ± 5; p = 0.09). There were no statistical differences in the cumulative survival rate at 2 yr (propranolol plus sclerotherapy, 74% ± 6% and propranolol alone, 64% ± 6%) or in the number of patients who died of repeat bleeding (propranolol plus sclerotherapy, 13% ± 4% and propranolol alone, 17% ± 5%). Among the surviving patients, cirrhosis improved during the follow–up; Child–Pugh classification was the following at 1 mo: 35% for class A, 50% for class B and 15% for class C and the following at 2 yr: 58% for class A, 38% for class B and 4% for class C. In conclusion, elective sclerotherapy does not significantly decrease the rate of recurrent bleeding or death in severely cirrhotic patients who are treated with propranolol and who mainly abstain from drinking alcohol. (HEPATOLOGY 1992;16:912-919.)