tbuckley/cabot-search huggingface dataset:
<i>nab</i>-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer
Authors: Kristopher K. Frese, Albrecht Neesse, Natalie Cook, Tashinga E. Bapiro, Martijn P. Lolkema, Duncan I. Jodrell, David A. Tuveson
Journal: Cancer Discovery (2012)

Abstract Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics have limited our ability to address the mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA to show that the coadministration of nab-paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. Combination treatment increases intratumoral gemcitabine levels attributable to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase. Correspondingly, paclitaxel reduced the levels of cytidine deaminase protein in cultured cells through reactive oxygen species–mediated degradation, resulting in the increased stabilization of gemcitabine. Our findings support the concept that suboptimal intratumoral concentrations of gemcitabine represent a crucial mechanism of therapeutic resistance in PDA and highlight the advantages of genetically engineered mouse models in preclinical therapeutic trials. Significance: This study provides mechanistic insight into the clinical cooperation observed between gemcitabine and nab-paclitaxel in the treatment of pancreatic cancer. Cancer Discovery; 2(3); 260–9. ©2012 AACR. Read the Commentary on this article by Clark, p. 208 This article is highlighted in the In This Issue feature, p. 193
PROGNOSTIC VALUES OF MULTIDETECTOR COMPUTED TOMOGRAPHY IN PATIENTS WITH KNOWN OR SUSPECTED CORONARY ARTERY DISEASE
Authors: So Yeon Kim, Kee-Sik Kim, Myeung Joon Seung, Jung Hyeun Kim, Jin Wook Jung, Seung Hee Moon, Young Soo Lee, Jin Bae Lee, Jae Kean Ryu, Ji Young Choi, Sung-Gug Chang
Journal: Journal of the American College of Cardiology (2010)
Juxtaposition of the Atrial Appendages
Authors: YZHAR CHARUZI, PANAYIOTIS K. SPANOS, KURT AMPLATZ, JESSE E. EDWARDS
Journal: Circulation (1973)

Juxtaposition of the atrial appendages refers to that condition in which both atrial appendages or one and part of the other lie beside each other and to one side of the great arterial vessels. The appendages lying to the left of the great vessels (left-sided juxtaposition) is considerably more common than the state in which the appendages lie to the right of the great vessels (right-sided juxtaposition) by a ratio of about 6:1. Among left-sided juxtaposition it is common that the right atrial appendage be bifid and that only its left unit be "juxtaposed." Such a state is termed "bifid atrial appendage with partial juxtaposition." Juxtaposition almost always is associated with significant congenital heart disease in which transposition of the great vessels is commonly a feature. Tricuspid atresia with transposition or complete transposition are the two conditions most commonly associated with juxtaposition. Recognition of juxtaposition as an entity may serve, under certain circumstances, as an aid in the evaluation of an angio-cardiogram.
Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival
Authors: Josep M. Llovet, Jordi Bruix
Journal: Hepatology (2003)

There is no standard treatment for patients with unresectable hepatocellular carcinoma (HCC). Survival benefits derived from medical interventions are controversial. The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival. Randomized controlled trials (RCTs) that were published as full papers assessing survival for primary treatments of HCC were included. MEDLINE, the Cochrane Library, CANCERLIT, and a manual search from 1978 to May 2002 were used. The primary end point was survival, and the secondary end point was response to treatment. Estimates of effect were calculated according to the random effects model. Sensitivity analysis included methodological quality. We identified 61 randomized trials, but only 14 met the criteria to perform a meta-analysis assessing arterial embolization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with control (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.89; P = .017). Sensitivity analysis showed a significant benefit of chemoembolization with cisplatin or doxorubicin (OR, 0.42; 95% CI, 0.20-0.88) but none with embolization alone (OR, 0.59; 95% CI, 0.29-1.20). Overall, treatment induced objective responses in 35% of patients (range, 16%-61%). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI, 0.36-1.13; P = .13), and only low-quality scale trials suggested 1-year improvement in survival. In conclusion, chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Treatment with tamoxifen does not modify the survival of patients with advanced disease.
A novel IgM class autoantibody to a hepatocyte-related 190 kDa molecule in patients with type 1 autoimmune hepatitis
Authors: Katsumi Yamauchi, Naoko Yamaguchi, Takaji Furukawa, Kazuko Takatsu, Toshimi Nakanishi, Mina Sasaki, Etsuko Isono, Katsutoshi Tokushige, Tatsuji Komatsu, Keiko Shiratori
Journal: Hepatology (2004)

It has been reported that autoantibodies to hepatocytes are frequently found in patients with autoimmune hepatitis (AIH). To elucidate the nature of these hepatocyte-specific autoantibodies, we attempted to generate a hepatocyte-specific monoclonal antibody (MoAb) from Epstein-Barr virus-transformed peripheral blood mononuclear cells obtained from a patient with AIH. We established a single clone, 2E3, that continued to produce an immunoglobulin M (IgM) antibody (λ-type). This MoAb had the following properties: it reacted mainly with hepatocyte-derived cell lines, rather than with other cell lines, and it reacted with liver tissue but not with other tissues. By immunoblot analysis, we found that this MoAb recognized a 190 kDa molecule on hepatocytes. The MoAb was able to kill hepatocyte-derived cell lines in the presence of fresh human serum. This cytotoxic effect was completely abrogated by heat inactivation of human serum prior to its addition to cell lines. In addition, an IgM autoantibody that recognized a 190 kDa molecule was also found in patients with AIH but not in those with chronic hepatitis C; its titer correlated significantly with serum alanine aminotransferase (ALT) levels in patients with AIH. In conclusion , we generated a human MoAb that recognizes a 190 kDa molecule on hepatocytes. Because of its ability to mediate complement-dependent cytotoxicity and the presence of similar IgM autoantibody in patients with AIH, we hypothesize this autoantibody may play a role in the immunopathogenesis of AIH. (Hepatology 2004;40:687-692.)
Birth Weight and Genital Mycoplasmas in Pregnancy
Authors: Peter Braun, Yhu-Hsiung Lee, Jerome O. Klein, S. Michael Marcy, Thomas A. Klein, David Charles, Paul Levy, Edward H. Kass
Journal: New England Journal of Medicine (1971)

To ascertain the relation between mycoplasmas in the cervix and urine of pregnant women and the outcome of pregnancy, 485 patients were studied prospectively in the prenatal clinic of the Boston City Hospital. T-strains were recovered from 384 women who gave birth to babies whose mean birth weight was 202 g (7.1 oz) less than that of the babies of women from whom T-strains were not isolated (p less than 0.003). Mycoplasma hominis, which was often associated with T-strains in cultures of the urine and cervix, was less well linked with low birth weight (p equal to 0.054). The association of T-strains with low birth weight was not related to shortened gestational length. The presence of T-strains in the urine and cervix was independent of other risk factors for low birth weight. T-strains or M. hominis were not related to history of previous premature births, stillbirths or abortions or to the development of toxemia or third-trimester hemorrhage.
Baroreflex responsiveness in borderline hypertensives: a study with neostigmine
Authors: B. TRIMARCO, M. VOLPE, B. RICCIARDELLI, C. VIGORITO, L. SACCA, F. RENGO, M. CONDORELLI
Journal: Cardiovascular Research (1981)

Journal Article Baroreflex responsiveness in borderline hypertensives: a study with neostigmine Get access BRUNO TRIMARCO, BRUNO TRIMARCO * From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy *Address for reprint requests: Bruno Trimarco, MD, Istituto di Patologia Medica, Via S Pansini 5, 80131 Napoli, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar MASSIMO VOLPE, MASSIMO VOLPE From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar BRUNO RICCIARDELLI, BRUNO RICCIARDELLI From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar CARLO VIGORITO, CARLO VIGORITO From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar LUIGI SACCA, LUIGI SACCA From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar FRANCO RENGO, FRANCO RENGO From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar MARIO CONDORELLI MARIO CONDORELLI From the Istituto di Patologia Medica, 2° Facolta di Medicina e Chirurgia, Universita di Napoli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 8, August 1981, Pages 436–442, https://doi.org/10.1093/cvr/15.8.436 Published: 01 August 1981
Therapeutic Targeting of a Robust Non-Oncogene Addiction to <i>PRKDC</i> in <i>ATM</i> -Defective Tumors
Authors: Arina Riabinska, Mathias Daheim, Grit S. Herter-Sprie, Johannes Winkler, Christian Fritz, Michael Hallek, Roman K. Thomas, Karl-Anton Kreuzer, Lukas P. Frenzel, Parisa Monfared, Jorge Martins-Boucas, Shuhua Chen, Hans Christian Reinhardt
Journal: Science Translational Medicine (2013)

Treating ATM-deficient cancers with an inhibitor of DNA-PKcs induces apoptosis due to inability to repair double-strand breaks in DNA.
Abstract 1408: Nicotine decreases the therapeutic efficacy of radiotherapy and chemoradiotherapy in vivo
Authors: Graham W. Warren, Marcus Randall, Ronald McGarry, Mahesh Kudrimoti, Vivek Rangnekar
Journal: Cancer Research (2010)

Abstract Background: Continued tobacco use during cancer treatment has been associated with poor outcome. Nicotine replacement is currently used as a standard of care for smoking cessation in cancer patients; however, prior data demonstrates that nicotine can promote tumor growth and decrease the effectiveness of cancer treatment in vitro. Methods: Athymic nude mice with human H460 lung cancer cell xenografts were stratified into three Groups beginning when tumors reached 5 mm in maximal dimension: control (CON), short term nicotine (STN, 60 ug subcutaneously every other day x 6 days), or long term nicotine (LTN, 60 ug SC every other day until tumor endpoint). Within each Group, mice were further stratified into three Treatments consisting of saline (SAL), radiotherapy (RT, 3 Gy daily x 5 days), or chemoradiotherapy (CRT, RT + concurrent cisplatin intraperitoneally 3 mg/kg daily x 5 days). Tumor volumes were measured and compared between Treatments and Groups (n=10 per Treatment within each Group). This protocol was approved by the Institutional Animal Care and Use Committee at the University of Kentucky. Results: In CON animals, RT (199 uL at day 30) or CRT (100 uL at day 30) significantly prevented tumor regrowth as compared with control SAL animals (864 uL at day 10 requiring euthanasia as per protocol). As expected, CRT was more effective than RT (p&amp;lt;0.05). Nicotine administration alone (STN or LTN) had no effect on tumor growth rate as compared with CON. In contrast, administration of LTN significantly increased tumor regrowth in RT animals (356 uL at day 30, p&amp;lt;0.05) and CRT treated animals (170 uL ad day 30, p&amp;lt;0.05). To eliminate the effects of nicotine on proliferation following completion of RT or CRT, animals were treated with STN. Administration of STN also significantly increased tumor regrowth in RT animals (328 uL at day 30, p&amp;lt;0.05) and CRT animals (176 uL at day 30, p&amp;lt;0.05) with virtually identical regrowth curves as demonstrated for LTN animals. Conclusions: Results demonstrate that nicotine significantly reduces the efficacy of RT and CRT in vivo. Moreover, data suggest that nicotine use during treatment is the primary determinant of decreased therapeutic response. These results may significantly alter current recommendations for smoking cessation in cancer treatment populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1408.
Sports and Streaking
Authors: Hugh H. Hussey
Journal: JAMA (1974)

Physicians, like other normal persons, have an abiding interest in athletic competitions. For most physicians, the interest is purely vicarious as spectators, but not for all. At the national level, the AMA Committee on Medical Aspects of Sports has sponsored annual conferences that have had an important influence on promoting safety in equipment, methodology, and usage for sports adventures. JAMA has honored the Olympic Games with special issues, the last published Aug 28, 1972. On the local level, some physicians have given unstintingly and without monetary recompense of their time as team physicians for high school football teams. An example is Julian P. Price, MD, pediatrician, past trustee of the AMA Board of Trustees, who served 14 years as advisor, partial coach, and healer to the high school football team in his home town, Florence, SC. For the professional athletes, of course, physicians are serving more or less full time,
MENTAL DISEASE IN RUSSIA
Authors: James Page
Journal: American Journal of Psychiatry (1938)

Psychiatric work in Russia today is organized somewhat along the lines of public health work in this country. In each community there is a district psychiatrist who is responsible for the mental health of his district The most marked point of difference between psychiatry in Russia and in other countries is that a greater attempt is made, by an adjustment of working conditions, to adapt the environment to the patient. With respect to the types of mental disease and the basic psychopathic manifestations, there do not appear to exist any differences between Russia and other countries. The Soviet régimehas brought about a change in the content of mental symptoms, but there is no evidence that it has either decreased the incidence of mental disease or altered the basic forms of mental disease.
Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia
Authors: I. Martín-Loeches, J. F. Bermejo-Martin, J. Vallés, R. Granada, L. Vidaur, J. C. Vergara-Serrano, M. Martín, J. C. Figueira, J. M. Sirvent, J. Blanquer, D. Suarez, A. Artigas, A. Torres, E. Diaz, A. Rodriguez
Journal: Intensive Care Medicine (2013)
Thyroxine-binding globulin, hyperthyroxinemia and hepatocellular carcinoma Huang M-J, Liaw Y-F. Thyroxine-binding globulin in patients with chronic hepatitis B virus infection: different implications in hepatitis and hepatocellular carcinoma. Am J Gastroentol 1990;85:281–284
Authors: M Kew
Journal: Hepatology (1991)
Studies on the role of the host immune response in recovery from Friend virus leukemia. I. Antiviral and antileukemia cell antibodies.
Authors: B Chesebro, K Wehrly
Journal: The Journal of Experimental Medicine (1976)

The humoral immune response to Friend virus leukemia was studied in congenic F1 mice differing in their incidence of recovery from leukemia. Antiviral neutralizing antibodies rose in titer in vivo concurrently with disappearance of viremia and fall in spleen virus levels. Cytotoxic antileukemia cell antibodies also appeared at this time. Passive transfer of these antibodies could inactivate low numbers of leukemia cells in vivo; however, mice of both high and low recovery genotypes produced antibodies in equal titer and recovered from viral infection in spite of striking differences in recovery from leukemic splenomegaly. Mice lacking C57BL genes did not produce antibodies or recover from viremia except in rare instances. Recovery from splenomegaly was found to be influenced by three or more C57BL genes independent of the H-2 complex.
Probing In Vivo Trafficking of Polymer/DNA Micellar Nanoparticles Using SPECT/CT Imaging
Authors: Rajesh R Patil, Jianhua Yu, Sangeeta R Banerjee, Yong Ren, Derek Leong, Xuan Jiang, Martin Pomper, Benjamin Tsui, Dara L Kraitchman, Hai-Quan Mao
Journal: Molecular Therapy (2011)

Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with 111In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles. Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with 111In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles.
Localization of Hemorrhage in a Recurrent Hemothorax Using Tc-99m-Sulfur Colloid
Authors: RAYMOND TAILLEFER, RICHARD ESSIAMBRE, RAYMOND LEMIEUX
Journal: Clinical Nuclear Medicine (1981)

Tc-99m-sulfur colloid scintigraphy has proven clinically useful in identifying gastrointestinal hemorrhages. The authors describe a patient with recurrent hemothorax under oral anticoagulation therapy in which Tc-99m-sulfur colloid imaging was used to determine the site of bleeding.
Hypersensitivity reactions from inhalation of milk proteins
Authors: A. Vargiu, G. Vargiu, F. Locci, S. Del Giacco, G. S. Del Giacco
Journal: Allergy (1994)

We describe the case of a young man with IgE‐mediated hyper sensitivity to milk, casein, and lactoglobulin, who went into respiratory crisis every time he milked his sheep.
Is<i>Chlamydia pneumoniae</i>an important pathogen in patients with community-acquired pneumonia?
Authors: S. Ewig, A. Torres
Journal: European Respiratory Journal (2003)

Chlamydia pneumoniae has been established as a respiratory pathogen since 1986, when the association of this pathogen with respiratory infections was demonstrated by culture in a study of seroconverting patients in Seattle, USA, in 1984 1. Since then, the majority of studies evaluating the aetiology of community-acquired pneumonia (CAP) have reported the occurrence of C. pneumoniae in ∼10–20% of patients 2–8. Current guidelines published by the American Thoracic Society (ATS) 9, the Infectious Diseases Society of America (IDSA) 10, the Canadian Infectious Diseases Society, the Canadian Thoracic Society 11, the European Respiratory Society 12 and the British Thoracic Society (BTS) 13 all agree that C. pneumoniae is an important pathogen that should be covered when targeting empirical initial antimicrobial treatment.

Obviously, the variation of incidence rates across these studies is not only due to differences in the populations and geographical areas studied but also to inconsistencies in the methodologies used to establish acute C. pneumoniae infections. Whereas most studies applied serological methods, the criteria of seropositivity differed and only a minority of studies also included culture and/or molecular methods. To make things even more complicated, there is no generally accepted technique to firmly diagnose acute C. pneumoniae infection. Whereas complement fixation is only genus- and not species-specific, microimmunofluorescence is difficult to perform, has an important subjective element with regard to reading and remains open to diverse interpretations of seropositivity 14. Moreover, seropositivity is not irrefutably diagnostic of acute infection as positive serological tests were also found to occur in asymptomatic individuals in up to 20% …
Talks on climate change collapse in acrimony
Authors: P. Ghazi
Journal: BMJ (2000)

The world may have lost its “best chance” to combat global warming effectively after 180 countries failed to agree terms in The Hague last weekend, environmentalists have said.

Negotiations to agree concrete measures to implement the 1997 Kyoto protocol collapsed on Saturday after delegations representing the European Union and the United States failed to agree measures to curb the greenhouses gases heating the planet. An eleventh hour compromise, brokered by the United Kingdom's deputy prime minister, John Prescott, and involving significant US concessions, was rejected by Germany, France, Denmark, and Sweden.

As a result, climate talks remain in limbo until October 2001, when high level negotiations are due …