tbuckley/cabot-search huggingface dataset:
Abstract 2112: The role of reactive oxygen species (ROS) in cell death induced by thymidylate synthase inhibitors.
Authors: Ufuk Ozer, Karen W. Barbour, Franklin G. Berger
Journal: Cancer Research (2013)

Abstract Thymidylate synthase (TS) catalyzes the reductive transfer of a methyl group from N5,N10-methylenetetrahydrofolate (CH2H4PteGlu) to dUMP, forming dTMP and dihydrofolate (H2PteGlu). It is generally accepted that inhibition of the enzyme leads to a deficiency of dTMP, followed by genome damage and programmed cell death. As such, TS has long been viewed as an important target of anti-neoplastic agents, such as 5-fluorouracil (FUra) and ratitrexed (RTX), which function as inhibitors of the enzyme. Oxidative stress is well-recognized as having a central role in cellular response to a number of DNA damaging agents, and may be a proximate cause of therapy-induced cell death. Despite such recognition, little detail exists on the origin and regulation of reactive oxygen species (ROS) during TS-directed chemotherapy. We have undertaken a detailed examination of the origin, nature, and role of ROS in cell death mediated by TS inhibitors. In colon tumor cell line HCT116, fluorescence detection of H2O2 and O2•− (using H2DCFDA and DHE, respectively) showed that profound increases in ROS levels occur during drug exposure. These increases are attenuated by treatment with the antioxidant N-acetylcysteine (NAC), by addition of thymidine to the medium and by TS overproduction, indicating that it is indeed TS inhibition and the resulting dTMP deficiency that is responsible. Oxidative damage to DNA, as indicated by 8-oxo-guanine formation, is elevated in drug-treated cells. Apoptotic indices, as measured by TUNEL assays, parallel changes in ROS levels, i.e., they are induced in response to drug, and are inhibited by NAC, thymidine, and TS overproduction. We have identified NADPH oxidase (NOX) as the primary source of increased ROS following exposure to TS-directed agents, as indicated by observing decreased ROS production apoptotic indices in cells treated with NOX inhibitors. We have found that in response to TS inhibitors, NOX enzyme activity increases in association with induction of the transcript for p67phox, which specifically regulates the NOX2 isoform. These effects were reduced by thymidine and by TS overproduction. Based on these results, we conclude that augmentation of NOX2 activity via induction of p67phox mRNA expression is the proximate cause of programmed cell death elicited by dTMP deficiency. Citation Format: Ufuk Ozer, Karen W. Barbour, Franklin G. Berger. The role of reactive oxygen species (ROS) in cell death induced by thymidylate synthase inhibitors. [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 2112. doi:10.1158/1538-7445.AM2013-2112
Book: Narrative-based Primary Care: A Practical Guide
Authors: E. Rosenberg
Journal: BMJ (2003)

John Launer Radcliffe Medical Press, £21.95, pp 272 http://www.radcliffe-oxford.com/ Rating: ![Graphic][1]</img> ![Graphic][2]</img> ISBN 1 85775 539 1 As a general practitioner, I find the interviewing techniques presented in this book interesting. They look as if they might be useful to my patients and to me. Launer invites readers to structure their clinical conversations making use of the idea that knowledge occurs through the stories—the narratives—that we tell others and ourselves about our experiences. In a usual clinical encounter the patient brings his story about his condition (which he may get a chance to tell to the doctor). The clinician develops her story on the basis of what the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Diarrhea of Travelers-Reply
Authors: B. H. Kean
Journal: JAMA (1962)

<h3>To the Editor:—</h3> The term "San Franciscitis" mentioned in Dr. MacDonald's letter will be welcomed by our friends abroad who are often irritated by our tendency to regard travelers' diarrhea as an ailment acquired solely in their countries. After World War II, many visitors from Britain developed diarrhea in New York City. Theories as to etiology were numerous—approximately one per patient. We have on hand the prospectus for a project in which visitors to the United States will be asked to report on the incidence of diarrhea during their stay in this country.
Scientists build a peptide to stop toxic shock syndrome
Authors: J. Siegel-Itzkovich
Journal: BMJ (2000)

A potential weapon against the virulent strains of staphylococcal and streptococcal bacteria that produce toxic shock syndrome has been developed by Israeli researchers and has been found to be effective in mice.

The research team, whose breakthrough is described in this month's Nature Medicine (2000;6:414-21) was headed by Raymond Kaempfer, professor of molecular virology at the Hebrew University-Hadassah faculty of medicine in Jerusalem. He and Dr Gila Arad, Revital Levy, and Dalia Hillman spent four years planning and building a synthetic peptide antagonist that blocks …
Role of Semen Cryobanking in American Medicine
Authors: M. S. Frankel
Journal: BMJ (1974)

In the United States there is little public policy regulating the activities of semen cryobanks. The medical profession has also been conspicuously silent on this aspect of medical practice. The potential benefits of semen cryobanking are enormous, yet like all other technologies its application (particularly commercially) may produce unexpected and unwanted consequences. It is suggested that a co-operative effort is needed between public officials and the medical profession to establish standards and guidelines which would maximize the benefits of this technique.
Nucleofection of DCs to Generate Multivirus-specific T Cells for Prevention or Treatment of Viral Infections in the Immunocompromised Host
Authors: Ulrike Gerdemann, Anne S Christin, Juan F Vera, Carlos A Ramos, Yuriko Fujita, Hao Liu, Dagmar Dilloo, Helen E Heslop, Malcolm K Brenner, Cliona M Rooney, Ann M Leen
Journal: Molecular Therapy (2009)

Viral infections cause morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. To prevent and treat these, we have produced and infused cytotoxic T lymphocytes (CTLs) with specificity for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and adenovirus (Adv), and shown that small numbers of infused cells proliferate in vivo and protect against all three viruses. Despite these encouraging results, broader implementation of this approach is limited by the need for infectious virus material (EBV), expensive production of clinical grade adenoviral vectors, and a prolonged (8–12 weeks) period of manufacture. There is also competition between virus-derived antigens within antigen-presenting cells (APCs), limiting extension to additional agents. We now describe an approach that uses DNA nucleofection of dendritic cells (DCs) with DNA plasmids that encode a range of immunodominant and subdominant viral antigens from CMV, EBV, BK, and Adv. Within 10 days, this methodology provides multivirus-reactive CTLs that lack alloreactivity. We further demonstrate that nucleofected DC stimulation can be combined with interferon-γ (IFN-γ) capture technology to produce even more rapid multivirus-CTL products for treatment of acute infection. These CTL generation procedures should increase the feasibility and applicability of T-cell therapy. Viral infections cause morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. To prevent and treat these, we have produced and infused cytotoxic T lymphocytes (CTLs) with specificity for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and adenovirus (Adv), and shown that small numbers of infused cells proliferate in vivo and protect against all three viruses. Despite these encouraging results, broader implementation of this approach is limited by the need for infectious virus material (EBV), expensive production of clinical grade adenoviral vectors, and a prolonged (8–12 weeks) period of manufacture. There is also competition between virus-derived antigens within antigen-presenting cells (APCs), limiting extension to additional agents. We now describe an approach that uses DNA nucleofection of dendritic cells (DCs) with DNA plasmids that encode a range of immunodominant and subdominant viral antigens from CMV, EBV, BK, and Adv. Within 10 days, this methodology provides multivirus-reactive CTLs that lack alloreactivity. We further demonstrate that nucleofected DC stimulation can be combined with interferon-γ (IFN-γ) capture technology to produce even more rapid multivirus-CTL products for treatment of acute infection. These CTL generation procedures should increase the feasibility and applicability of T-cell therapy.
Recognition of Postoperative Acute Myocardial Infarction
Authors: SEWELL H. DIXON, LEE E. LIMBIRD, CHARLES R. ROE, GALEN S. WAGNER, H. NEWLAND OLDHAM, DAVID C. SABISTON
Journal: Circulation (1973)

Routine enzymatic and electrocardiographic diagnosis of postoperative acute myocardial infarction (AMI) is frequently inconclusive. The detection and quantitation of isoenzymes of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), especially the cardiac-specific CPK-MB isoenzyme, have allowed earlier recognition of AMI in nonsurgical patients. Serial monitoring with these methods has been utilized during the postoperative period in 20 noncardiac surgical patients and 100 patients undergoing coronary artery bypass grafting (CABG). In the noncardiac surgery group, both isoenzymes were accurate in diagnosing AMI in the early postoperative period. Of the 100 patients in the CABG group, CPK-MB appearance in 21 correlated with AMI by electrocardiogram. The absence of CPK-MB postoperatively in 49 patients permitted a 73% incidence of new ECG abnormalities to be effectively resolved. Autopsy confirmation of AMI was obtained in two patients with nondiagnostic ECG, but with elevated CPK-MB. The elevated CPK-MB without ECG evidence of AMI in the remaining patients could possibly be explained by varying degrees of myocardial damage produced by intraoperative cardiac manipulation. These data demonstrate the value and sensitivity of CPK-MB isoenzyme determinations in the early recognition of postoperative acute myocardial infarction.
Prevalence and Health-Care Features of Hyperglycemia in Semiurban-Rural Communities in Southern Saudi Arabia
Authors: Hassan A H Abu-Zeid, Abdul Salam K Al-Kassab
Journal: Diabetes Care (1992)

Objective To determine the prevalence of hyperglycemia in semiurban-rural Saudi Arabian communities and to assess some of its important health-care related aspects. Research Design and Methods A cluster of 12 villages near the city of Abha, the capital of the southern region in Saudi Arabia, with a total population of 2150 (290 families) has been included in this study. The family head was interviewed about diagnosed diabetes among family members. Also, the capillary blood glucose level was measured in subjects ≥ 10 yr (the target population, n = 1419) with a reflectance meter after 2-h fasting after the main midday meal. Results The 87% of the target population who responded for screening showed a prevalence of 4.6% of diabetes, which was higher among men (5.5%, age adjusted, P &amp;lt;0.05) than among women (3.6%). Estimates were based on 57 cases ascertained by positive history of the disease (n = 49) or blood glucose level ≥ 11.1 mM (200 mg/dl) without previous diagnosis of diabetes (n = 8). The prevalence of impaired glucose tolerance (blood glucose between 7.8 (140 mg/dl) and 11.0 mM (199 mg/dl) with no history of diabetes) was 3.7%, being higher among women than among men (P &amp;lt;0.01). Eighty-eight percent of the previously diagnosed cases were receiving treatment at the time of screening. However, in only 12.2% of those receiving treatment was glucose found to be controlled (level &amp;lt;7.8 mM [140 mg/dl]). Conclusions Diabetes frequency in this Saudi community is relatively high. There is a pressing need to promote public awareness about the disease and to improve the competency of the health-care team for achieving better control and early detection of the disease.
Monoclonal antibody-based method to quantify Gly m 1. Its application to assess environmental exposure to soybean dust
Authors: R. González, O. Duffort, B. Calabozo, D. Barber, J. Carreira, F. Polo
Journal: Allergy (2000)

Background: The demonstration that some asthma epidemics have been caused by allergens of soybean‐hull dust prompted us to develop a two‐site ELISA, suitable for the quantification of the major allergen (Gly m 1), to be used for the prevention of new episodes. Methods: BALB/c mice were injected with Gly m 1 purified from soybean hulls. After fusion and screening, 10 monoclonal antibodies (mAbs) were obtained that were shown to be specific for Gly m 1. Two of them (6G1 as the capture antibody; 1G10 as the tracer) were selected to develop a quantitative two‐site ELISA for the indoor and outdoor determination of Gly m 1. Results: The two‐site ELISA developed is very sensitive, with a detection limit of less than 0.2 ng/ml and a practical working range of 0.4–10 ng/ml. The assay is also highly reproducible with an intra‐assay coefficient of variation of 3.5% and an interassay coefficient of variation of 12.5%. The method was applied to measure the concentration of Gly m 1 in air‐sampler filters and in house‐dust samples. Our results illustrate that there is a good correlation between the content of Gly m 1 in a number of samples and the allergenic activity as measured by ELISA inhibition. Conclusions: A specific and sensitive method is presented that can be used for the quantification of Gly m 1. The application of this method may allow the establishment of risk limits for soybean dust, and thus may contribute to the control of environmental contamination and to the prevention of new asthma epidemics.
Agent Orange and Spontaneous Abortions
Authors: Ralph R. Cook
Journal: JAMA (1980)

<h3>To the Editor.—</h3> I read with interest the recent MEDICAL NEWS column "Plenty of Fuel for Agent Orange Dispute" (242:593, 1979). As indicated, the Environmental Protection Agency (EPA) recently implemented an emergency suspension of the herbicide 2,4,5-trichlorophenoxy acetic acid (2,4,5-T), citing as justification the Alsea study. Unfortunately,The Journalarticle erroneously reported "130 spontaneous abortions [occurred] within three months (following the spraying of 2,4,5-T)." In fact, during the entire 72-month period covered by this EPA research, only 188 spontaneous abortions were reported to have occurred in the study area—about 2.6 per month. I suspect Mr Gunby meant 130 spontaneous abortions per 1,000 live births. Even this deserves comment. The rate presumes the researchers had valid data for both the numerator (spontaneous abortions) and the denominator (live births). They had neither. For spontaneous abortions, they used<i>hospitalized</i>early spontaneous abortions (less than 20 weeks' gestation) and thus produced numbers for study and
Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response.
Authors: J R Beach, C L Young, A J Avery, S C Stenton, J H Dennis, E H Walters, D J Hendrick
Journal: Thorax (1993)

BACKGROUND: The value of measuring airway responsiveness in asthma research is currently limited by the number of different methods used by different investigators, by the lack of a standardised method of expressing precision, and by an inability to equate the results of one method with those of another. METHODS: Two pairs of measurements of airway responsiveness to methacholine were performed in 20 asthmatic subjects, one pair using a dosimeter method (AR-D) and one pair using the conventional Wright nebuliser tidal breathing method (AR-W). The two methods normally use different techniques for quantifying changing levels in forced expiratory volume in one second (FEV1) after each dose of methacholine (the mean of the highest three of six measurements for AR-D, the lower of two measurements for AR-W), and different techniques for expressing measurements of airway responsiveness (the provoking dose (PD20) and the provoking concentration (PC20) respectively responsible for a 20% decrement in FEV1). RESULTS: The coefficient of repeatability (and hence precision) for the measurement of airway responsiveness was significantly better for AR-D (3.0) than for AR-W (10.9), but the technique for quantifying FEV1 contributed more to this than the technique for delivering methacholine. A PC20 of 1 mg/ml with AR-W was equivalent to a PD20 of 103 micrograms with AR-D. CONCLUSIONS: It is practical as well as desirable to compare the precision of different techniques for the measurement of airway responsiveness and to derive conversion factors so that results may be equated.
The effect of <i>BDNF</i> gene variants on asthma in German children
Authors: S. Zeilinger, L. A. Pinto, W. A. Nockher, M. Depner, N. Klopp, T. Illig, E. Von Mutius, H. Renz, M. Kabesch
Journal: Allergy (2009)

Background: Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain‐derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation. Aim: We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. Methods: The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross‐sectional study population of 3099 children from Dresden and Munich (age 9–11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi‐square test and anova using SAS Genetics and spss . Results: We identified nine polymorphisms with minor allele frequency ≥0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross‐sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14–1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70–0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00–1.42, P = 0.05). Conclusions: As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma.
"Benign" Versus "Malignant" Antinuclear Antibodies.
Authors: George J. Friou
Journal: Annals of Internal Medicine (1969)

s1 May 1969"Benign" Versus "Malignant" Antinuclear Antibodies.George J. Friou, M.D., F.A.C.P., Takeshi Tojo, M.D.George J. Friou, M.D., F.A.C.P.Search for more papers by this author, Takeshi Tojo, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1088_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn certain patients antinuclear antibodies are "benign" while in systemic lupus with nephritis they are involved in production of nephritis by deposition as immune complexes with nuclear antigens and complement. We have found that, in the former, complement-fixing activity of such antibodies is low, even though present in large amounts, while in lupus nephritis complement-fixing activity is high.Relative complement-fixing activity of antinuclear antibodies was determined by comparing titers in the complement fluorescent technique with titers by conventional antinuclear antibodies. Patients included active lupus nephritis (15), other systemic lupus erythematosus patients (26), rheumatic arthritis (20), chronic active hepatitis (7), and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: George J. Friou, M.D., F.A.C.P.; Takeshi Tojo, M.D.Affiliations: Los Angeles, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5 Page: 1088-1088 Keywords Antibodies Antigens Antinuclear antibodies Chronic hepatitis Immune complex Lupus erythematosus Lupus nephritis Nephritis Rheumatic fever ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
Deletion of cytosolic phospholipase A2 promotes striated muscle growth
Authors: Syed Haq, Heiko Kilter, Ashour Michael, Jingzang Tao, Eileen O'Leary, Xio Ming Sun, Brian Walters, Kausik Bhattacharya, Xin Chen, Lei Cui, Michele Andreucci, Anthony Rosenzweig, J. Luis Guerrero, Richard Patten, Ronglih Liao, Jeffery Molkentin, Michael Picard, Joseph V. Bonventre, Thomas Force
Journal: Nature Medicine (2003)
PHENOBARBITAL AND AMYTAL IN STRYCHNINE POISONING
Authors: Howard W. Haggard
Journal: JAMA (1933)

<h3>To the Editor:</h3> —In April, 1932, we published a report of an investigation on the antagonism between strychnine and phenobarbital sodium (Antidotes for Strychnine Poisoning,The Journal, April 2, 1932, p. 1133). In our experiments, carried out on rats and dogs, we found that phenobarbital in large doses controlled strychnine convulsions and allowed recovery after five times the lethal dose of strychnine and that, conversely, strychnine acted as an antidote for phenobarbital sodium, allowing recovery after amounts three times that of the lethal dose. M. C. Wheelock (Strychnine Poisoning,The Journal, Nov. 26, 1932, p. 1862) has recently reported a case of strychnine poisoning in which convulsions were controlled and a fatal outcome averted by the administration of 0.3 Gm. of phenobarbital sodium and 1.3 Gm. of sodium amytal given intravenously. E. E. Swanson (<i>J. Lab. &amp; Clin. Med.</i><b>17</b>:325 [Jan.] 1932) has found experimentally that amytal sodium acts
THE DISTRIBUTION OF SWINE INFLUENZA VIRUS IN SWINE
Authors: Marion L. Orcutt, Richard E. Shope
Journal: The Journal of Experimental Medicine (1935)

Swine influenza virus was found to be regularly present in the turbinates, tracheal exudate and lungs of infected swine but not in the spleens, livers, kidneys, mesenteric lymph nodes, colon mucosae, brains or blood. It was present in low concentration in the bronchial lymph nodes of 2 out of 8 animals. This localization of the virus in swine accords with its classification as a pneumotropic virus.
Coronary heart disease: then and now
Authors: P. D. White
Journal: JAMA (1968)

Two years after James Herrick<sup>1</sup>published in<i>The Journal of the American Medical Association</i>in 1912 his classical paper on coronary thrombosis Richard Cabot<sup>2</sup>published, also inThe Journal, his important paper on the causes of heart disease in which he said that "the ravages of arterial disease and perhaps many other causes may produce the lesions of chronic fibrous myocarditis, with or without recognizable symptoms. A diagnosis of myocarditis is like a diagnosis of 'ulcer'; it calls for an etiologic qualification." In that paper Cabot analyzed 600 cases of heart disease with failure seen at the Massachusetts General Hospital and attributed the types or causes as follows: rheumatic heart disease 278, nephritic 117, arteriosclerotic 93, and syphilitic 74; there were also 8 goiter hearts and 30 cases not classified. He went on to say that those with "arteriosclerotic" heart disease "often live many years in comparative comfort. On