tbuckley/cabot-search huggingface dataset:
TP53-independent Function of miR-34a via HDAC1 and p21CIP1/WAF1
Authors: Jane Zhao, Paul Lammers, Chris J Torrance, Andreas G Bader
Journal: Molecular Therapy (2013)

The tumor suppressor, microRNA-34 (miR-34), a transcriptional target of TP53, functions in a positive feedback loop to activate TP53. Although miR-34 can inhibit cancer cells carrying TP53 mutations, this feedback to TP53 may be a prerequisite for full miR-34 function and may restrict its therapeutic application to patients with intact TP53. To investigate the functional relationships between TP53 and miR-34, and that of other TP53-regulated miRNAs including miR-215/192, we have used a panel of isogenic cancer cell lines that differ only with respect to their endogenous TP53 status. miR-34–induced inhibition of cancer cell growth is the same in TP53-positive and TP53-negative cells. In contrast, miR-215/192 functions through TP53. In the absence of TP53, miR-34, but not miR-215/192, is sufficient to induce an upregulation of the cell cycle-dependent kinase inhibitor p21CIP1/WAF1. We identify histone deacetylase 1 (HDAC1) as a direct target of miR-34 and demonstrate that repression of HDAC1 leads to an induction of p21CIP1/WAF1 and mimics the miR-34 cellular phenotype. Depletion of p21CIP1/WAF1 specifically interferes with the ability of miR-34 to inhibit cancer cell proliferation. The data suggest that miR-34 controls a tumor suppressor pathway previously reserved for TP53 and provides an attractive therapeutic strategy for cancer patients irrespective of TP53 status. The tumor suppressor, microRNA-34 (miR-34), a transcriptional target of TP53, functions in a positive feedback loop to activate TP53. Although miR-34 can inhibit cancer cells carrying TP53 mutations, this feedback to TP53 may be a prerequisite for full miR-34 function and may restrict its therapeutic application to patients with intact TP53. To investigate the functional relationships between TP53 and miR-34, and that of other TP53-regulated miRNAs including miR-215/192, we have used a panel of isogenic cancer cell lines that differ only with respect to their endogenous TP53 status. miR-34–induced inhibition of cancer cell growth is the same in TP53-positive and TP53-negative cells. In contrast, miR-215/192 functions through TP53. In the absence of TP53, miR-34, but not miR-215/192, is sufficient to induce an upregulation of the cell cycle-dependent kinase inhibitor p21CIP1/WAF1. We identify histone deacetylase 1 (HDAC1) as a direct target of miR-34 and demonstrate that repression of HDAC1 leads to an induction of p21CIP1/WAF1 and mimics the miR-34 cellular phenotype. Depletion of p21CIP1/WAF1 specifically interferes with the ability of miR-34 to inhibit cancer cell proliferation. The data suggest that miR-34 controls a tumor suppressor pathway previously reserved for TP53 and provides an attractive therapeutic strategy for cancer patients irrespective of TP53 status.
Grwoth Inhibition of Mouse MXT Mammary Tumor by the Luteinizing Hormone-Releasing Hormone Antagonist SB-75
Authors: B. Szende, G. Srkalovic, k. Groot, K. Lapis, A. V. Schally
Journal: JNCI Journal of the National Cancer Institute (1990)

Female BDF 1 mice bearing MXT mammary adenocarcinomas were treated for 3 weeks with the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2) 1 , D-Phe(4Cl) 2 , D-Pal(3) 3 , D-Cit 6 , D-Ala 10 ]-LH-RH (SB-75), with the agonist D-Trp 6 -LH-RH, with tamoxifen (5 μg per animal per day subcutaneously), with the combination of D-Trp 6 -LH-RH and tamoxifen, or by surgical ovariectomy. SB-75 and D-Trp 6 -LH-RH were administered in the form of microscapsules releasing 25 μg/day. The reduction in tumor weights after treatment with SB-75, D-Trp 6 -LH-RH, D-Trp 6 -LH-RH plus tamoxifen, or overiectomy was 84%, 64%, 33%, and 67%, respectively. Tamoxifen alone was ineffective. Histologically, the regressive changes in the treated tumors were characteristic of apoptosis (programmed cell death). In view of its potency and its immediate inhibitory effect, the LH-RH antagonist SB-75 should be considered as a possible new hormonal agent for the treatment of breast cancer. [J Natl Cancer Inst 82:513–517, 1990]
Subclass-restricted IgG polyclonal antibody production in mice injected with lipid A-rich lipopolysaccharides.
Authors: S Izui, R A Eisenberg, F J Dixon
Journal: The Journal of Experimental Medicine (1981)

The effects of five distinct bacterial lipopolysaccharides (LPS) on the induction of polyclonal IgM and IgG antibodies, including polyclonal autoantibody formation, were investigated in several strains of mice. Injections of most LPS preparations that contained polysaccharide transiently induced only IgM polyclonal antibodies. However, LPS from Salmonella minnesota R595 (R595 LPS), which had a particularly high content of lipid A but lacked O-antigen polysaccharide, induced a markedly prolonged IgM and IgG polyclonal antibody response in mice, including athymic nude mice, but not in LPS-unresponsive C3H/HeJ mice. Polyclonal IgM and IgG production peaked in sera on day 8 and day 15, respectively, and remained higher than control values 2 mo after the injection. The IgG induced by R595 LPS was strictly restricted to IgG2b and Igg3 subclasses in normal mice. In contrast, in athymic nude mice which have normally lower levels of IgG1 and IgG2a than normal mice, R595 LPS stimulated the production of all the IgG subclasses and reconstituted serum levels of IgG1 and IgG2a up to, but not higher than, control values of normal mice. These findings suggest that different mechanisms regulate production of each IgG subclass after stimulation with LPS.
Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
Authors: Christopher I Amos, Xifeng Wu, Peter Broderick, Ivan P Gorlov, Jian Gu, Timothy Eisen, Qiong Dong, Qing Zhang, Xiangjun Gu, Jayaram Vijayakrishnan, Kate Sullivan, Athena Matakidou, Yufei Wang, Gordon Mills, Kimberly Doheny, Ya-Yu Tsai, Wei Vivien Chen, Sanjay Shete, Margaret R Spitz, Richard S Houlston
Journal: Nature Genetics (2008)
Localization of proteolytic activity in psoriatic skin.
Authors: L. DUBERTRET, B. BERTAUX, M. FOSSE, R. TOURAINE
Journal: British Journal of Dermatology (1982)

Journal Article Localization of proteolytic activity in psoriatic skin. Get access L. DUBERTRET, L. DUBERTRET Laboratoire de Dermatologie, Hopital Henri‐Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar B. BERTAUX, B. BERTAUX Laboratoire de Dermatologie, Hopital Henri‐Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar M. FOSSE, M. FOSSE Laboratoire de Dermatologie, Hopital Henri‐Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar R. TOURAINE R. TOURAINE Laboratoire de Dermatologie, Hopital Henri‐Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 5, 1 November 1982, Pages 499–504, https://doi.org/10.1111/j.1365-2133.1982.tb00398.x Published: 01 November 1982 Article history Accepted: 11 June 1982 Published: 01 November 1982
Effect of once daily and twice daily sustained release theophylline formulations on daytime variation of bronchial hyperresponsiveness in asthmatic patients
Authors: M. Ferrari, M. Olivieri, G. Lampronti, L. Bonazza, C. Biasin, P. Nacci, G. Talamini, V. Lo Cascio
Journal: Thorax (1997)

BACKGROUND: Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the prototype theophylline given twice a day. The aim of this study was to compare the effects on bronchial responsiveness to methacholine of an ultrasustained release theophylline formulation (Diffumal-24, Malesci, Florence, Italy) administered once a day, a sustained release theophylline formulation (Theo-Dur, Recordati, Milan, Italy) administered twice a day, and placebo. METHODS: The study was performed in 12 adult patients with asthma using a randomised, double blind, three phase, cross-over design. Each phase lasted seven days and was followed or preceded by at least three days of theophylline washout. Diffumal-24 was administered once a day at 20.00 hours whereas Theo-Dur was given twice a day at 08.00 hours and 20.00 hours. In each patient the total daily dose of theophylline was the same during both phases. The dose of the two active preparations was titrated to individual needs before the beginning of the study and then given in divided or once daily doses. At 08.00, 14.00, and 20.00 hours on day 7 of each phase serum theophylline concentrations were measured and spirometric tests (FEV1) and bronchial challenge with methacholine were also performed. RESULTS: When the administration of Diffumal-24 was compared with that of Theo-Dur, a higher serum theophylline concentration of the former was seen in the morning whereas at 20.00 hours the reverse was true. Compared with placebo, at 08.00 hours Diffumal-24 improved FEV1 whereas Theo-Dur did not (difference between treatments 0.29 1, 95% CI 0.12 to 0.45). At 08.00 hours Diffumal-24 decreased bronchial sensitivity to methacholine, expressed as a natural logarithm of PD20, to a greater extent than Theo-Dur (difference between treatments 0.54 log units, 95% CI 0.016 to 1.08). The morning advantage observed with Diffumal-24 administration was not associated with a deterioration in the state of the airway during the daytime, the protective activity against methacholine during the 12 hours of the monitoring period being constant. Furthermore there was no difference in the mean FEV1 between the two treatments at 14.00 and 20.00 hours. CONCLUSIONS: In adults with stable bronchial asthma treatment with a single dose of Diffumal-24 administered in the evening improved airflow obstruction and reduced bronchial hyperresponsiveness.
Epidemic Neuropathy in Cuba
Authors: Eliseo Perez-Stable
Journal: Annals of Internal Medicine (1995)

Letters1 November 1995Epidemic Neuropathy in CubaEliseo Perez-Stable, MDEliseo Perez-Stable, MDUniversity of Miami; Miami, FL 33125Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-9-199511010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Roman's article describing an epidemic of neurologic disease in Cuba is comprehensive and well documented [1]. I wholeheartedly agree that “physicians may need to use their influence to modify political decisions when these decisions result in adverse health consequences.” Nevertheless, I do not agree that the U.S. embargo and the breakdown of the Soviet Union are the principal causes of the problems affecting Cuba in the 1990s. Undoubtedly, the U.S. embargo and its tightening through the Cuban Democracy Act of 1992 are a heavy burden on the Cuban government, particularly given the collapse of the eastern Europe ...References1. Roman GC. On politics and health: an epidemic of neurologic disease in Cuba. Ann Intern Med. 1995; 122:530-3. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Miami; Miami, FL 33125 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTreatment and Outcomes in Nutritional Optic NeuropathyToxic optic neuropathyNutritional Amblyopia and B Complex Vitamin Deficiencies 1 November 1995Volume 123, Issue 9Page: 734KeywordsFoodNeuropathyNutritionPublic policy Issue Published: 1 November 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Introduction to Human Parasitology.
Authors: Asa Crawford Chandler
Journal: JAMA (1930)

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
Molecular identification of major and minor bullous pemphigoid antigens
Authors: Xue-Jun Zhu, Yayoi Niimi, Jean-Claude Bystryn
Journal: Journal of the American Academy of Dermatology (1990)

The skin antigens defined by basement membrane zone antibodies in 38 patients with bullous pemphigoid were analyzed by Western immunoblot. Thirty-four patients (89%) had antibodies to a major bullous pemphigoid antigen with a molecular weight of approximately 230 kD. Twelve patients (32%) had antibodies to a minor bullous pemphigoid antigen with a molecular weight of approximately 160 kD; this included four patients who did not have antibodies to the 230 kD antigen. Depending on the epidermal extract used, a variable number of patients (up to 75%) also had antibodies to minor bullous pemphigoid antigens with molecular weights of approximately 180 and 200 kD. The results of this study confirm that bullous pemphigoid antigens are heterogeneous at the molecular level. Approximately 10% of patients have antibodies directed solely to a minor bullous pemphigoid antigen.
Mechanical properties and in vitro response of strontium-containing hydroxyapatite/polyetheretherketone composites
Authors: K.L. Wong, C.T. Wong, W.C. Liu, H.B. Pan, M.K. Fong, W.M. Lam, W.L. Cheung, W.M. Tang, K.Y. Chiu, K.D.K. Luk, W.W. Lu
Journal: Biomaterials (2009)
DNA Probes
Authors: Frank E. Young
Journal: JAMA (1987)

The emergence of recombinant DNA technology in the 1970s has given rise to new diagnostic techniques based on DNA probes. The Food and Drug Administration's interest in these probes stems from its regulatory responsibilities regarding DNA probes as medical devices. The agency also sees DNA probes as valuable tools in meeting its mission of identifying, preventing, and resolving public health problems, especially in the area of food safety. The development of DNA probes for genetic diseases is raising medical and ethical questions that must be addressed by the medical community, whose ultimate responsibility must be to see that this new technology is used wisely, appropriately, and correctly.The author writes about DNA probes, a spin-off technology from recombinant DNA research, from two perspectives: that of a physician, and that of the federal Commissioner of Food and Drugs. Young discusses the Food and Drug Administration's role in regulating DNA probes, as well as the agency's interest in using the probes to confront public health problems such as food pathogens. He also comments on some aspects of molecular biology's growing role in medicine. Young emphasizes that the FDA's responsibility for regulating DNA probes is limited, and that the medical community is obligated to ensure that the probes are used appropriately as diagnostic aids, particularly when screening for genetic disease.
Case 54-1965
Authors: Thomas C. Chalmers, Wallace A. Jones
Journal: New England Journal of Medicine (1965)

Presentation of CaseA fifty-one-year-old woman was admitted to the hospital because of jaundice.She had been well until two years previously, when she began to have night sweats, which occurred intermittently until three months before admission. Five months before entry there was the onset of progressive fatigue, and four months later marked anorexia developed. Within two weeks icterus and dark urine were observed, and during the week before admission the stools became light.Her consumption of alcohol was believed to have been excessive in the recent past. There was no history of exposure to tuberculosis or hepatitis, transfusions, injections, . . .
Tetanus Toxoid Immunization of Adults: A Continuing Need
Authors: GEO. F. BROOKS
Journal: Annals of Internal Medicine (1970)

In recent years in the United States tetanus has become a disease primarily of adults; there were about five times more tetanus deaths in the 35 years and older age group than for persons 1 to 34 years of age. The mean age at death, excluding neonates, has risen from 25 years in previous years to over 50 years in the late 1960's. Data strongly suggest the need for improved immunization of adults. A schedule for such immunization is provided.
Some problematic links between hunting and geometry
Authors: Meredith M. Kimball
Journal: Behavioral and Brain Sciences (1996)

Abstract Geary's emphasis on hunting ignores the possible importance of other human activities, such as scavenging and gathering, in the evolution of spatial abilities. In addition, there is little evidence that links spatial abilities and math skills. Furthermore, such links have little practical importance given the small size of most differences and girls' superior performance in mathematics classrooms.
Stroke, Tachyarrhythmia, and Propranolol
Authors: Stephen Mizroch
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The study of Feibel et al (238:1374-1376) and our successful use of propranolol hydrochloride to treat a tachyarrhythmia in a stroke patient prompted us to report the following case. <h3>Report of a Case.—</h3> A 57-year-old man had arteriosclerosis and cerebral vascular disease, a history of congestive heart failure, and chronic atrial fibrillation well controlled with digoxin. He became dizzy and weak. On physical examination he was agitated, diaphoretic, and in modest respiratory distress. The blood pressure was 160/100 mm Hg, and pulse rate was 140 beats per minute and irregularly irregular. There were no murmurs, gallops, or rubs. He had a dense left hemiparesis with total left-sided sensory deficit and hyperactive reflexes. An ECG showed atrial fibrillation with a rate of 140 to 160 beats per minute. The CBC count and electrolytes, Po<sub>2</sub>, triiodothyronine, thyroxine, and digoxin levels were all within normal limits. As the patient
Unstable insertion in the 5′ flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1
Authors: Ronald G. Lafreniére, Daniel L. Rochefort, Nathalie Chrétien, Johanna M. Rommens, Jeffrey I. Cochius, Reetta Kälviäinen, Unto Nousiainen, George Patry, Kevin Farrell, Birgitta Söderfeldt, Antonio Federico, Bradford R. Hale, Otto Hernandez Cossio, Troels Sørensen, Marc A. Pouliot, Tomasz Kmiec, Peter Uldall, József Janszky, Michael R. Pranzatelli, Frederick Andermann, Eva Andermann, Guy A. Rouleau
Journal: Nature Genetics (1997)
Treatment of Hypertension with Propranolol
Authors: B. N. C. Prichard, P. M. S. Gillam
Journal: BMJ (1969)

When used in the treatment of hypertension propranolol is at least of similar potency to bethanidine, guanethidine, and methyldopa. Propranolol does not produce postural or exercise hypotension and it seems that it is often more acceptable to patients than conventional drugs. It usually produces the best control of the supine blood pressure.A series of 109 hypertensive patients was treated with propranolol; in nine the drug was withdrawn. In 92 of the patients a supine or standing blood pressure of 100 mm. Hg or less was achieved. Eighty of the patients had previously been treated with other potent drugs, and close comparisons and prolonged follow-up in 17 patients showed that diastolic pressures of 100 mm. Hg or less were achieved in more patients after propranolol than with guanethidine, bethanidine, or methyldopa.Sensitivity to propranolol varies widely, and dosage should be increased gradually. The hypotensive effect often takes six to eight weeks to reach its maximum. Propranolol reduces cardiac output but may also act by reducing the cardiac component of pressor stimuli; as a result the baroreceptors gradually regulate the blood pressure at a lower level. It is contraindicated in patients with obstructive airways disease or in uncompensated heart failure.
A New Series on the Revolution in Immunology
Authors: Robert A. Goldstein, Anthony S. Fauci
Journal: New England Journal of Medicine (1987)

There was a time when it appeared to be relatively easy to comprehend immunology. Reflecting the historical successes of cowpox inoculation against smallpox, of rabies and polio vaccines, and of passive immunizations with antitoxins, immunity came to mean freedom from infection. However, further studies demonstrated that the activity of the immune system could have potentially harmful effects as well.By the early 1970s, when Dr. Dorland Davis, then director of the National Institute of Allergy and Infectious Diseases (NIAID), convened a panel to "evaluate present knowledge on immunology and its role in the cause, prevention and treatment of disease," it . . .
Role of K+ATP channels in coronary vasodilation during exercise.
Authors: D J Duncker, N S Van Zon, J D Altman, T J Pavek, R J Bache
Journal: Circulation (1993)

BACKGROUND The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular smooth muscle K+ATP channels in regulating coronary blood flow under resting conditions, during increments in myocardial metabolic demand produced by treadmill exercise, and in response to a brief ischemic stimulus. METHODS AND RESULTS Ten chronically instrumented dogs were studied at rest and during a four-stage exercise protocol under control conditions and during intracoronary infusion of the K+ATP channel blocker glibenclamide at rates of 10 and 50 micrograms.kg-1 x min-1. Glibenclamide (50 micrograms.kg-1 x min-1) decreased coronary blood flow at rest from 51 +/- 4 to 42 +/- 6 mL/min (P &lt; .05), decreased myocardial oxygen consumption from 5.70 +/- 0.31 to 4.11 +/- 0.56 mL O2/min (P &lt; .05), and decreased systolic wall thickening from 21 +/- 3% to 12 +/- 3% (P &lt; .05). The depression of systolic wall thickening produced by glibenclamide was reversed when coronary blood flow was restored to the control level with intracoronary nitroprusside, indicating a primary effect of glibenclamide on coronary flow during resting conditions. However, glibenclamide did not impair the increases of coronary blood flow, myocardial oxygen consumption, and systolic wall thickening that occurred during exercise. In eight resting awake dogs, 50 micrograms.kg-1 x min-1 glibenclamide decreased the peak reactive hyperemia blood flow rate following a 20-second coronary occlusion from 149 +/- 14 mL/min during control conditions to 111 +/- 15 mL/min (P &lt; .05), decreased the duration of reactive hyperemia from 49 +/- 6 to 33 +/- 3 seconds (P &lt; .05), and decreased reactive hyperemia excess flow from 33 +/- 5 to 20 +/- 4 mL (P &lt; .05). CONCLUSIONS These data demonstrate that K+ATP channels modulate coronary vasomotor tone under resting conditions and contribute to coronary vasodilation during ischemia. However, the coronary vasculature retains the capacity to dilate in response to increases in oxygen demand produced by exercise when K+ATP channels are blocked.