tbuckley/cabot-search huggingface dataset:
Intratumoral Delivery of p2CMVmIL-12 Using Water-Soluble Lipopolymers
Authors: Ram I Mahato, Minhyung Lee, Sang-oh Han, Anurag Maheshwari, Sung Wan Kim
Journal: Molecular Therapy (2001)

Our objective was to design a water-soluble lipopolymer (WSLP) and an interleukin-12 (IL-12) expression plasmid for enhanced delivery of the IL-12 gene. We synthesized WSLP using branched polyethylenimine (PEI) of 1800 Da and cholesteryl chloroformate, and constructed p2CMVmIL-12, encoding the IL-12 subunits p35 and p40, each under the transcriptional control of a separate cytomegalovirus (CMV) promoter. The percentage of cholesterol conjugated to PEI was about 47% and the average molecular weight of WSLP was approximately 2000 Da. The mean particle size of WSLP/p2CMVmIL-12 complexes formulated in 5% glucose was 26 to 62 nm and ξ potential was 8 to 60 mV. The WSLP/p2CMVmIL-12 complexes were nontoxic to CT-26 colon carcinoma cells at the N/P ratio (nitrogen atoms of WSLP/phosphate of plasmid DNA) of 20 and below; PEI25000/pDNA complexes were highly toxic. WSLP/p2CMVmIL-12 complexes demonstrated higher transfection in CT-26 cells compared with the DNA formulations prepared using PEI of molecular weights 1800, 10,000 and 25,000 Da. Transfection efficiency increased with an increase in N/P ratios from 5 to 15, then there was no significant increase in transfection up to the N/P ratio of 30/1. There was an increase in the level of IL-12 when free or complexed p2CMVmIL-12 was compared with free or complexed pIRESmIL-12 in which the p35 and p40 subunits were linked to the internal ribosome entry sites (IRES). At 48 hours post-injection of WSLP/p2CMVmIL-12 complexes into BALB/c mice bearing CT-26 subcutaneous tumors, the levels of IL-12, IFN-γ, and nitric oxide (NO) in the supernatant of the cultured tumors were higher for the WSLP/p2CMVmIL-12 complexes than for the naked p2CMVmIL-12, WSLP, and 5% glucose injected groups. There was a significant improvement in the survival rate and the inhibition of tumor growth after a single injection of WSLP/p2CMVmIL-12 complexes. We have designed an effective, nontoxic WSLP and an IL-12 expression plasmid with two CMV promoters.
P2-12-10: Low TCR Diversity (Divpenia) Is a Prognosis Factor of Overall Survival in Metastatic Breast Cancer.
Authors: M Manuel, O Tredan, T Bachelot, G Parmentier, A Courtier, T Rabeony, S Chabaud, J-F Mouret, A Grives, S Perez, G Clapisson, J-Y Blay, C Caux, N Pasqual, C Menetrier-Caux
Journal: Cancer Research (2011)

Abstract Background: We already showed that lymphopenia (&amp;lt;1000 lymphocytes/μl) or CD4+ T cell lymphopenia (&amp;lt;450/μl) detected before initiation of chemotherapy are prognostic factors for toxicity and death for metastatic breast cancer (MBC) patients. The goal of the present study was to identify the characteristics of the T cells in these lymphopenic patients. TCR diversity was investigated and tested as a prognostic factor for overall survival (OS). Patients and methods: The ImmunTraCkeR® assay (ImmunID, Grenoble, France), which analyzes through semi quantitative multiplex-PCR the V-D-J combinatorial diversity of TCR-beta chain (TRB), was used to investigate diversity of T cell repertoire on cryopreserved blood samples from a retrospective cohort of MBC patients before chemotherapy administration (n=66). Univariate and multivariate analysis were performed. We then validated our score on a prospective cohort (n=67) using the same eligibility criteria (MBC patients before first line chemotherapy administration). Results: Using a 33% cutoff for divpenia in our retrospective cohort (T cell diversity below 33%) (average diversity for healthy people is 70%), divpenia was associated with a median OS of 10 months vs 22 months for patients with diversity &amp;gt;33% (logrank p value=0.04). The NDL® score (Numeration Diversity Lymphocytes representation) that combines lymphocyte numeration with TRB diversity, demonstrated that lympho-divpenia (T cell diversity below 33% and lymphopenia below lGiga/L) was associated with a poor OS compared to patients with either lymphocyte &amp;lt;1000/μL &amp; diversity &amp;gt;33% or lymphocyte &amp;gt;1000/μL &amp; diversity &amp;lt;33% or both lymphocyte &amp;gt;1000/μL and diversity &amp;gt;33% (p=0.015). In multivariate analysis, including performance status (PS), hemoglobin level, polynuclear neutrophil count (PNN), age, and liver metastasis, NDL® score was identified as an independent prognostic factor for OS. In our prospective validation cohort, NDL® score was also identified as a prognostic factors for OS (p=0,007), as well as lymphopenia (&amp;lt;1000/μL) (p=0,0003), CD4+ lymphopenia (&amp;lt;450/μL) (p=0,04), menopausal status (p=0,02), hormonal receptor status (estrogen receptor p=0.02; progesterone receptor p=0.002) and lung metastasis (p=0,009). In multivariate analysis, hemoglobin level was the only independent prognostic factor in this cohort. Conclusion: We showed that Divpenia and NDL® score are prognostic factors for OS in MBC patients. In order to confirm these results, a prospective clinical trial is ongoing on a larger cohort of MBC and lung cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-10.
EFFECT OF EXPLOSIVE-TYPE STRENGTH TRAINING AND SHORT-TERM DETRAINING ON RATE OF TORQUE DEVELOPMENT DURING ISOMETRIC KNEE EXTENSION
Authors: Y Kobayashi, K Hirayama, T Matsubayashi, R Akagi
Journal: British Journal of Sports Medicine (2013)

Rate of torque development (RTD) is considered important for improving the performance in sports requiring explosive strength. Although RTD was reported to be increased after explosive-type strength training (Tillin et al . Exp Physiol 2012;97:630–41.), the effect of subsequent detraining on the increased RTD remains unclear. Therefore, this study aimed to investigate the effect of explosive-type strength training and subsequent short-term detraining on RTD during isometric knee extension. Ten male subjects participated in this study. They underwent explosive-type strength training for 6 weeks (3 days per week) and detraining for 3 weeks. The training consisted of four sets of 10 repetitions of explosive contractions of less than 1 s. At the pre- and post-training phases (PRE and POST, respectively) and after the detraining phase (DE), we measured the quadriceps femoris muscle thickness using ultrasonography. In addition, we measured the maximum voluntary torque (MVT) during maximum voluntary isometric knee extension of 3–5 s and RTD during explosive isometric knee extension of less than 1 s. In PRE, POST and DE, quadriceps femoris muscle thickness did not change. In POST, MVT and RTD increased compared with those in PRE ( p &lt;0.05). In DE, no change was observed in MVT compared with that in POST. However, in DE, RTD decreased compared with that in POST ( p &lt;0.05). In addition, no difference was observed between PRE and DE. These findings suggest that RTD increased after the 6-week explosive-type strength training but returned to the pre-training level after the 3-week short-term detraining. It is necessary to take into account the time point at which we evaluate the effect of training after explosive-type strength training.
STUDIES OF THE HEMOLYSIS OF RED BLOOD CELLS BY MUMPS VIRUS
Authors: Merle L. Moberly, Guido V. Marinetti, Robert F. Witter, Herbert R. Morgan
Journal: The Journal of Experimental Medicine (1958)

Evidence from microscopic studies indicates that hemolysis caused by the mumps virus hemolysin is a chemical type of hemolysis. Chromatographic analyses of the reaction mixture of erythrocytes and mumps virus following hemolysis indicate that hemolysis is not due to the action of a lecithinase A and that lysolecithin does not play a part in this process. The alteration of a component of the erythrocyte similar to sphingomyelin suggests that some of the phosphatides other than lecithin may be either directly or indirectly affected in the process of hemolysis of red blood cells by the mumps virus.
Elucidation of the therapeutic enhancer mechanism of poly-S-nitrosated human serum albumin against multidrug-resistant tumor in animal models
Authors: Yu Ishima, Marie Hara, Ulrich Kragh-Hansen, Aki Inoue, Ayaka Suenaga, Toshiya Kai, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama
Journal: Journal of Controlled Release (2012)
COALMINER'S PNEUMOCONIOSIS
Authors: P. Ellman
Journal: BMJ (1960)

<b>PURPOSE</b> Patients with serious psychiatric problems experience difficulty accessing primary care. The goals of this study were to assess whether care managers improved access and to understand patients’ experiences with health care after a psychiatric crisis. <b>METHODS</b> A total of 175 consecutive patients seeking care in a psychiatric emergency department were randomly assigned to an intervention group with care managers or a control group. Brief, semistructured interviews about health care encounters were conducted at baseline and 1 year later. Five raters, using the content-driven, immersion-crystallization approach, analyzed 112 baseline and year-end interviews from 28 participants in each group. The main outcomes were patients’ responses about their care experiences, connections with primary care, and integration of medical and mental health care. Scores for physical function and mental function were compared by analysis of variance (ANOVA). <b>RESULTS</b> At baseline, most participants described negative experiences in receiving care and emphasized the importance of listening, sensitivity, and respect. Fully 71% of patients in the intervention group said that having a care manager to assist them with primary care connections was beneficial. Patients in the intervention group had significantly better physical and mental function than their counterparts in the control group at 6 months (<i>P</i> = .03 for each) but not at 12 months. There was also a trend toward functional improvement over the course of the study in the intervention group. <b>CONCLUSIONS</b> This analysis suggests that care management is effective in helping patients access primary care after a psychiatric crisis. It provides evidence on and insight into how care may be delivered more effectively for this population. Future work should assess the sustainability of care connections and longer-term patient health outcomes.
Heart Disease Risk Factors and Hormone Use in Postmenopausal Women
Authors: Elizabeth Barrett-Connor
Journal: JAMA (1979)

A population of 1,496 women aged 55 to 74 years was studied for the distribution of heart disease risk factors in the presence or absence of postmenopausal estrogens. Current hormone use was reported by 39%. Hormone users were significantly slimmer than nonusers at all ages. After adjustment for the effect of obesity, hormone users had significantly lower mean levels of plasma cholesterol and higher mean levels of plasma triglycerides than nonusers. Blood pressure and fasting plasma glucose concentration tended to be lower among hormone users, although the differences were not statistically significant in all age groups. This article discusses the theoretical implications of these observations for cardiovascular disease mortality and contrasts them with the cancer risk of postmenopausal estrogen use. (<i>JAMA</i>241:2167-2169, 1979)
Relapsing organising pneumonitis in a man with primary biliary cirrhosis, CREST syndrome, and chronic pancreatitis.
Authors: A G Davison, O Epstein
Journal: Thorax (1983)

We report a relapsing, steroid-responsive, organising pneumonitis, in a man with the CREST syndrome (cal- cinosis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly, and telangiectasia) variant of systemic sclerosis and primary biliary cirrhosis.This pattern of pul- monary disease has not previously been described in sys- temic sclerosis.The association between primary biliary cirrhosis and the CREST syndrome is well recognised in women' and we report the association in a man.
The casualties that never arrived
Authors: S. Gottlieb
Journal: BMJ (2001)

We were watching the monstrous attacks unfold on television, when we saw the spectral image of the World Trade Center's south tower collapsing.We were stunned.We had watched in horror as the second airliner crashed into the south tower on live television.But none of us thought that the building could fall down.Minutes later, our pagers went off.We were told that residents should report to the hospital for an emergency mobilisation.When we arrived
Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines
Authors: Peter W.J. Kowalski-Saunders, Paul J. Winwood, Michael J.P. Arthur, Ralph Wright
Journal: Hepatology (1992)

Decreased albumin synthesis by hepatocytes in liver injury is thought to occur in response to Kupffer cell-derived acute-phase cytokines. In this study we used hepatocytes maintained in a differentiated phenotype, by culture on a laminin-rich gel substratum (Engelbreth-Holm-Swarm matrix), to investigate the effects of Kupffer cell-conditioned medium and purified cytokines (interleukin-1, interleukin-6 and tumor necrosis factor-alpha) on albumin synthesis. Kupffer cell-conditioned medium caused a reversible decrease in albumin synthesis to 64.7% of control (p less than 0.01, Wilcoxon's rank sum test, n = 11) on day 2. Repeated doses caused further dose-dependent reversible responses. The same result was obtained when protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation. Pure interleukin-1, interleukin-6 and tumor necrosis factor-alpha also inhibited albumin synthesis (p less than 0.05, Wilcoxon's rank sum test, n = 5), interleukin-6 having the greatest effect. After exposure to interleukin-1 (30 U.ml-1) and tumor necrosis factor-alpha (300 U.ml-1), decreased albumin synthesis was followed by a rebound increase (n = 3). Our results support the hypothesis that reduced albumin synthesis in the acute-phase response is modulated by cytokines released from Kupffer cells. Moreover, our results suggest that hepatocytes may exhibit a compensatory increase in albumin synthesis after cytokine withdrawal. These findings may be of physiological importance in the recovery from injury and the acute-phase response in vivo.
Comment on "The Origins of Sexually Transmitted HIV Among Men Who Have Sex with Men"
Authors: Laura Heath, Lisa M. Frenkel, Brian T. Foley, James I. Mullins
Journal: Science Translational Medicine (2010)

Unexpected diversity of HIV strains in infected patients reported by Butler et al . indicates that there are problems with the validity of the analysis and, therefore, the conclusion that seminal plasma is the main source of infecting virus.
Ranitidine, Acetaminophen, and Hepatotoxicity
Authors: JAMES E. BREDFELDT
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 November 1984Ranitidine, Acetaminophen, and HepatotoxicityJAMES E. BREDFELDT, M.D., CHRISTIAN VON HUENE, M.D.JAMES E. BREDFELDT, M.D., CHRISTIAN VON HUENE, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-5-719_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Ranitidine, a recently marketed H2-receptor antagonist, is considered to have a low potential for hepatotoxicity (1). Two recent reports have described possible cases of ranitidine hepatotoxicity (2, 3). We report an additional case of cholestatic hepatitis, possibly related to ranitidine.A 42-year-old man developed a duodenal ulcer while taking aspirin. Ranitidine, 150 mg twice a day, was prescribed. In place of aspirin, acetaminophen, four to six 325-mg tablets per day, was taken for the next several weeks. Three weeks after starting ranitidine, the patient noted dark urine. The patient had no symptoms of liver disease or cholestasis....References1. ZELDISFRIEDMANISSEL BACHER JLK. Ranitidine: a new H2-receptor antagonist. N Engl J Med. 1983;309:1368-73. CrossrefMedlineGoogle Scholar2. SOUZA LIMA M. Hepatitis associated with ranitidine. Ann Intern Med. 1984;101:207-8. LinkGoogle Scholar3. BLACKSCOTTKANTER MWR. Possible ranitidine hepatotoxicity. Ann Intern Med. 1984;101:208-10. LinkGoogle Scholar4. MCCARTHY D. Ranitidine or cimetidine [Editorial]. Ann Intern Med. 1983;99:551-3. LinkGoogle Scholar5. SPEEGCHRISTIANMITCHELL KDM. Ranitidine and acetominophen hepatotoxicity [Letter]. Ann Intern Med. 1984;100:315-6. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Lovelace Medical Center and University of New Mexico Albuquerque, NM 87108 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug Interactions with ParacetamolPossible Cholestatic Injury From Ranitidine With a Review of the Literature9 Drug-induced cholestasisRanitidine drug interactions—a literature reviewAdverse Reactions and Interactions with H2-Receptor AntagonistsGastrointestinal drugsRanitidine and the LiverMARCOS A. SOUZA LIMA, M.D. 1 November 1984Volume 101, Issue 5Page: 719-719KeywordsAspirinDuodenal ulcersHepatitisLiver diseasesUrine Issue Published: 1 November 1984 PDF downloadLoading ...
Human T cell clones express functional homing receptors required for normal lymphocyte trafficking.
Authors: R F Navarro, S T Jalkanen, M Hsu, G Søenderstrup-Hansen, J Goronzy, C Weyand, C G Fathman, C Clayberger, A M Krensky, E C Butcher
Journal: The Journal of Experimental Medicine (1985)

To function efficiently in vivo, lymphocytes must circulate from the blood into lymphoid tissues and other sites of immune reaction. Herein, we show that human cytotoxic and helper T cell clones and lines, maintained in vitro with IL-2, express the functional capacity to recognize and bind to high endothelial venules (HEV), a capacity essential for lymphocyte exit from the blood, and hence for normal lymphocyte trafficking. The expression of functional homing receptors distinguishes human T cell clones from their murine counterparts, which uniformly lack receptors for HEV and are unable to migrate normally from the blood in vivo. The results raise the possibility that human T cell clones may be more effective in mediating in vivo immune responses than is suggested by murine models.
DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication
Authors: Susan P. Whitman, Björn Hackanson, Sandya Liyanarachchi, Shujun Liu, Laura J. Rush, Kati Maharry, Dean Margeson, Ramana Davuluri, Jing Wen, Tatiana Witte, Li Yu, Chunhui Liu, Clara D. Bloomfield, Guido Marcucci, Christoph Plass, Michael A. Caligiuri
Journal: Blood (2008)
Aspirin and Risk of Hemorrhagic Stroke
Authors: Jiang He, Paul K. Whelton, Brian Vu, Michael J. Klag
Journal: JAMA (1998)

Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke.To estimate the risk of hemorrhagic stroke associated with aspirin treatment.Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files.All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported.Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol.Data from 16 trials with 55462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics.These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.
Feedback Reduces Test Use in a Health Maintenance Organization
Authors: Donald M. Berwick
Journal: JAMA (1986)

In a cross-over design, three interventions were tested for their impact on the rate of use of 12 commonly ordered blood tests and roentgenograms among internists in a health maintenance organization. Overall use fell by 14.2% in a 16-week period during which physicians received confidential feedback on their individual rates of use compared with peers (cost feedback). Eleven of 12 tests showed some decrease. Similar feedback on rates of abnormal test results (yield feedback) and a program of test-specific education failed to show a consistent effect. Variability in rates of test use among physicians, as measured by the coefficient of variation, fell by 8.3% with cost feedback, by 1.3% with yield feedback, and by 2.3% with education, but these changes were inconsistent across tests.
LKB1 Loss Induces Characteristic Patterns of Gene Expression in Human Tumors Associated with NRF2 Activation and Attenuation of PI3K-AKT
Authors: Jacob M. Kaufman, Joseph M. Amann, Kyungho Park, Rajeswara Rao Arasada, Haotian Li, Yu Shyr, David P. Carbone
Journal: Journal of Thoracic Oncology (2014)

Inactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene and protein expressions in a murine model of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (Kras)-mutant lung cancer have been studied to gain insight into the biology of these tumors. However, the molecular consequences of LKB1 loss in human lung cancer have not been fully characterized.We studied gene expression profiles associated with LKB1 loss in resected lung adenocarcinomas, non-small-cell lung cancer cell lines, and murine tumors. The biological significance of dysregulated genes was interpreted using gene set enrichment and transcription factor analyses and also by integration with somatic mutations and proteomic data.Loss of LKB1 is associated with consistent gene expression changes in resected human lung cancers and cell lines that differ substantially from the mouse model. Our analysis implicates novel biological features associated with LKB1 loss, including altered mitochondrial metabolism, activation of the nuclear respiratory factor 2 (NRF2) transcription factor by kelch-like ECH-associated protein 1 (KEAP1) mutations, and attenuation of the phosphatidylinositiol 3-kinase and v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway. Furthermore, we derived a 16-gene classifier that accurately predicts LKB1 mutations and loss by nonmutational mechanisms. In vitro, transduction of LKB1 into LKB1-mutant cell lines results in attenuation of this signature.Loss of LKB1 defines a subset of lung adenocarcinomas associated with characteristic molecular phenotypes and distinctive gene expression features. Studying these effects may improve our understanding of the biology of these tumors and lead to the identification of targeted treatment strategies.
Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila
Authors: Julien Séjourné, Pierre-Yves Plaçais, Yoshinori Aso, Igor Siwanowicz, Séverine Trannoy, Vladimiros Thoma, Stevanus R Tedjakumala, Gerald M Rubin, Paul Tchénio, Kei Ito, Guillaume Isabel, Hiromu Tanimoto, Thomas Preat
Journal: Nature Neuroscience (2011)