tbuckley/cabot-search huggingface dataset:
Leukemia inhibitory factor (LIF) stimulates proopiomelanocortin (POMC) expression in a corticotroph cell line. Role of STAT pathway.
Authors: D W Ray, S G Ren, S Melmed
Journal: Journal of Clinical Investigation (1996)

We recently described the expression of leukemia inhibitory factor (LIF) in human fetal and murine corticotrophs. LIF and the related cytokine oncostatin M induced basal, and corticotropin-releasing hormone (CRH) induced proopiomelanocortin (POMC) mRNA and ACTH secretion in AtT20 cells. LIF signaling and regulation of POMC gene transcription were therefore tested. Dexamethasone inhibited both basal- and LIF-induced ACTH secretion (P<0.05) and LIF induction of ACTH was also attenuated by immuneutralization of either the LIF receptor (35%, P<0.05) or the gp130 affinity converter (41%, P<0.05). These antisera also attenuated basal ACTH secretion in the absence of added ligand (P<0.05). To examine intrapituitary LIF signaling, phosphorylation of post-receptor substrates was measured. 1 nM LIF rapidly induced tyrosyl phosphorylation of STAT 1 and STAT 3 proteins, as well as tyrosyl phosphorylation of a 115-kD protein, coimmunoprecipitated with STAT 1. The transfected rat POMC promoter -706/+64, fused to the luciferase reporter gene, was induced by LIF, which exerted strong (18-fold) synergy with CRH. Deletion of the major CRH responsive region in POMC (-323/-166) abolished CRH induction of transcription and severely limited LIF synergy. Although 8 bromo cAMP or forskolin modestly enhanced POMC transcription (2.8-fold), LIF markedly potentiated (7.4-fold) these cAMP activators. These results demonstrate that corticotroph LIF action is receptor mediated and involves activation of STAT signaling pathways. LIF potently synergizes with both CRH and cAMP induction of POMC transcription. This novel intrapituitary signaling mechanism may mediate a neuroimmune pituitary interface.
Incidence and Clinical Implications of Isolation of Mycobacterium kansasii: Results of a 5-Year, Population-Based Study
Authors: Karen C. Bloch
Journal: Annals of Internal Medicine (1998)

Background: Mycobacterium kansasii, an unusual pathogen in the pre-AIDS era, is increasingly reported to cause infection among patients with HIV infection. Little is known about the epidemiology and clinical implications of M. kansasii infection in the AIDS era. Objective: To compare the incidence, demographic characteristics, and clinical features of M. kansasii infection in HIV-positive and HIV-negative persons. Design: Population-based laboratory surveillance. Setting: Three counties in northern California. Patients: All persons who had a positive culture for M. kansasii between 1 January 1992 and 31 December 1996. Measurements: Cumulative incidence rates were calculated for each year by dividing the number of adult patients by the annual estimated adult population. Demographic and socioeconomic data for a single county were obtained by linkage with the 1990 U.S. Census report. Results: 270 patients (69.3% of whom were HIV positive) were identified, for an incidence of 2.4 cases per 100 000 adults per year (95% CI, 2.1 to 2.7), 115 cases per 100 000 HIV-positive persons per year (CI, 99 to 133), and 647 cases per 100 000 persons with AIDS per year (CI, 554 to 751). Indicators of lower socioeconomic status were common among patients: Median incomes were $32 317 in census tracts in which cases were identified and $38 048 in census tracts without cases (P = 0.001), and 35.7% of patients had unstable housing situations. Ninety-four percent of cases were from respiratory isolates, and 87.5% of patients had evidence of infection. Persons with HIV infection differed from those without HIV infection with respect to mycobacteremia (9.6% compared with 0%; P = 0.001), need for hospitalization (77.4% compared with 51.9%; P < 0.001), and smear positivity (41.7% compared with 20.7%; P = 0.005). Chronic diseases were common among HIV-negative persons; however, 40.3% had no predisposing medical condition. Conclusions: Mycobacterium kansasii isolation is more common in HIV-positive persons, but most patients with M. kansasii infection have clinical and radiologic evidence of infection regardless of HIV status. Persons infected with HIV and M. kansasii have a higher rate of hospitalization and a greater burden of organisms. A possible association with poverty suggests mechanisms of transmission and requires further study.
Thrombin Induces Tumor Cell Cycle Activation and Spontaneous Growth by Down-regulation of p27Kip1, in Association with the Up-regulation of Skp2 and MiR-222
Authors: Liang Hu, Sherif Ibrahim, Cynthia Liu, Jeffrey Skaar, Michele Pagano, Simon Karpatkin
Journal: Cancer Research (2009)

Abstract The effect of thrombin on tumor cell cycle activation and spontaneous growth was examined in synchronized serum-starved tumor cell lines and a model of spontaneous prostate cancer development in TRAMP mice. BrdUrd incorporation and propidium iodide staining of prostate LNCaP cells arrested in G0 and treated with thrombin or serum revealed a 48- and 29-fold increase in S phase cells, respectively, at 8 hours. Similar results were obtained with TRAMP cells and a glioblastoma cell line, T98G. Cell cycle kinases and inhibitors in synchronized tumor cells revealed high levels of p27Kip1 and low levels of Skp2 and cyclins D1 and A. Addition of thrombin, TFLLRN, or serum down-regulated p27Kip1 with concomitant induction of Skp2, Cyclin D1, and Cyclin A with similar kinetics. LNCaP p27Kip1-transfected cells or Skp2 knockdown cells were refractory to thrombin-induced cell cycle activation. MicroRNA 222, an inhibitor of p27Kip1, was robustly up-regulated by thrombin. The in vitro observations were tested in vivo with transgenic TRAMP mice. Repetitive thrombin injection enhanced prostate tumor volume 6- to 8-fold (P &amp;lt; 0.04). Repetitive hirudin, a specific potent antithrombin, decreased tumor volume 13- to 24-fold (P &amp;lt; 0.04). Thus, thrombin stimulates tumor cell growth in vivo by down-regulation of p27Kip1. [Cancer Res 2009;69(8):3374–81]
Mortality falls if consultants work blocks of days rather than single day rotas, survey finds
Authors: L. Henderson, K. Vaghela
Journal: BMJ (2012)

An analysis of hospital rotas across England has found that having an admitting consultant present in acute medical units for more than one day at a time (in blocks of up to seven days) rather than on single days improves patients’ outcomes.

The survey, by the Royal College of Physicians, also found that mortality and readmissions fell when consultants conducted two or more ward rounds a day and had no other clinical commitments.

In a trust with a throughput of 44 300 acute patients a year, adopting this way of working could result in 100 …
A Screening Instrument for Sleep Apnea Predicts Airway Maneuvers in Patients Undergoing Advanced Endoscopic Procedures
Authors: Gregory A. Coté, Christine E. Hovis, Richard M. Hovis, Lawrence Waldbaum, Dayna S. Early, Steven A. Edmundowicz, Riad R. Azar, Daniel K. Mullady, Sreenivasa S. Jonnalagadda
Journal: Clinical Gastroenterology and Hepatology (2010)
Abstract 3926: Abrogating tamoxifen resistance with the ribonucleoside analog, 8-amino adenosine
Authors: Christine M. Stellrecht, Jennifer B. Dennison, Rachel Schiff, Shujun Shentu, Varsha Gandhi
Journal: Cancer Research (2012)

Abstract Hormone therapy is a prevalent treatment of choice for patients with estrogen receptor alpha (ERα) positive breast cancers. Unfortunately, due to resistance, many women do not benefit from these forms of therapy. AIB1 is a transcriptional co-activator that plays an important role in resistance to hormone therapy. Depending on the cell/gene context, agents such as tamoxifen either stimulate or antagonize the transcriptional activities of ERα. Tamoxifen binding alters ERα to an intermediate conformation with affinity for both co-activators and co-repressors, causing the conformation to be dependent on co-regulator levels in the cell milieu. The stoichiometric balance between AIB1 and co-repressors is a key determinant of tamoxifen resistance. Additionally, cross-talk between ERα and growth factor (GF) signaling further manipulates ERα activity and responsiveness to hormone therapy, particularly in cells with high AIB1 levels. Of the receptor signaling transducers, AKT, ERK, and p38 are key players in resistance. We hypothesized that strategies to target the stoichiometric balance of AIB1 to co-repressors would be clinically beneficial for abrogating tamoxifen resistance. Furthermore, it has been demonstrated that agents that are able to interfere with the ERα/GF crosstalk are also highly advantageous for abrogating resistance to tamoxifen. We have shown that the ribonucleoside analog, 8-aminoadenosine (8-NH2-Ado) is a transcription inhibitor. As such, it is expected to primarily deplete the expression of the small percentage (∼5%) of gene transcripts with short-half lives, such as AIB1. We have demonstrated that treatment of MCF-7 and BT-474 cells with non-tumoricidal concentrations of 8-NH2-Ado (1 µM) decreased AIB1 protein levels. Furthermore, using in vitro kinase assays, we demonstrated the active metabolite of 8-NH2-Ado is a selective inhibitor of MEK1, 2, and 6. An initial analysis of 4-hydroxytamoxifen dose response in two different tamoxifen resistant breast cancer cell lines, MCF-7/HER-2:18 and BT-474, demonstrated non-tumoricidal analog concentrations were able to reduce the dose of 4-hydroxytamoxifen needed to inhibit proliferation in these cells. Additionally, 8-NH2-Ado inhibited AKT and ERK1/2 activity in these cells. In conclusion, AIB1 and GF signaling molecules are attractive targets for reversing resistance to hormone therapy. Our results suggest that treating ERα positive breast cancer with combinations of tamoxifen and 8-NH2-Ado would be an effective strategy to overcome tamoxifen resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3926. doi:1538-7445.AM2012-3926
Psychosocial risk factors preceding overuse injury in floor-ball
Authors: U Tranaeus, U Johnson
Journal: British Journal of Sports Medicine (2011)

Background Previous research demonstrates an injury risk of traumatic and overuse injuries in floor-ball which is one of the major sports in Sweden with 1 24 000 licensed players. One important step to prevent overuse injuries to occur is to understand its psychosocial nature. Objective The aim of this study is to describe and structure athletes' experience of psychosocial risk factors preceding overuse injury. Design Elite floor-ball players were interviewed by the first author and based on a semi-structured interview guide. To uncover the underlying meaning in the transcribed interviews, a thematic content analysis was used. Setting Team doctors and physiotherapists in the highest floor-ball leagues (women and men), were contacted and asked to make contact with overuse injured players for interviews regarding their injury. Interviews were recorded at the interviewer's office or the floor-ball arena. The interviews were transcribed verbatim. Participants were informed about the purpose and the method of the study. That participation was voluntary, that their responses would be treated confidentially and that their identities would not be revealed in the reporting of the findings. Participants Nine male and one female elite floor-ball players diagnosed with a present overuse injury were recruited for voluntary participation. Main outcome measurements Psychosocial factors experienced by elite floor-ball players preceding overuse injuries. Assessment of risk factors Assessment is conducted through qualitative analysis. Results Three main themes evolved in the analysis; a) several players experienced pain while competing. However, it is difficult to separate normal/daily pain to warnings signals of an injury, b) many players experienced a culture in the team including not talking about their first symptoms, and, c) time for mental and physical recovery was not given during the season. Conclusion Players experienced a culture where it is not acceptable to talk about non traumatic pain. Periods of rest were limited leading to a need for mental recovery.
Adaptive Antiviral Immunity Is a Determinant of the Therapeutic Success of Oncolytic Virotherapy
Authors: Paul T Sobol, Jeanette E Boudreau, Kyle Stephenson, Yonghong Wan, Brian D Lichty, Karen L Mossman
Journal: Molecular Therapy (2010)

Oncolytic virotherapy, the selective killing of tumor cells by oncolytic viruses (OVs), has emerged as a promising avenue of anticancer research. We have previously shown that KM100, a Herpes simplex virus type-1 (HSV) deficient for infected cell protein 0 (ICP0), possesses substantial oncolytic properties in vitro and has antitumor efficacy in vivo, in part by inducing antitumor immunity. Here, we illustrate through T-cell immunodepletion studies in nontolerized tumor-associated antigen models of breast cancer that KM100 treatment promotes antiviral and antitumor CD8+ cytotoxic T-cell responses necessary for complete tumor regression. In tolerized tumor-associated antigen models of breast cancer, antiviral CD8+ cytotoxic T-cell responses against infected tumor cells correlated with the induction of significant tumoristasis in the absence of tumor-associated antigen-specific CD8+ cytotoxic T-cells. To enhance oncolysis, we tested a more cytopathic ICP0-null HSV and a vesicular stomatitis virus M protein mutant and found that despite improved in vitro replication, oncolysis in vivo did not improve. These studies illustrate that the in vitro cytolytic properties of OVs are poor prognostic indicators of in vivo antitumor activity, and underscore the importance of adaptive antiviral CD8+ cytotoxic T-cells in effective cancer virotherapy. Oncolytic virotherapy, the selective killing of tumor cells by oncolytic viruses (OVs), has emerged as a promising avenue of anticancer research. We have previously shown that KM100, a Herpes simplex virus type-1 (HSV) deficient for infected cell protein 0 (ICP0), possesses substantial oncolytic properties in vitro and has antitumor efficacy in vivo, in part by inducing antitumor immunity. Here, we illustrate through T-cell immunodepletion studies in nontolerized tumor-associated antigen models of breast cancer that KM100 treatment promotes antiviral and antitumor CD8+ cytotoxic T-cell responses necessary for complete tumor regression. In tolerized tumor-associated antigen models of breast cancer, antiviral CD8+ cytotoxic T-cell responses against infected tumor cells correlated with the induction of significant tumoristasis in the absence of tumor-associated antigen-specific CD8+ cytotoxic T-cells. To enhance oncolysis, we tested a more cytopathic ICP0-null HSV and a vesicular stomatitis virus M protein mutant and found that despite improved in vitro replication, oncolysis in vivo did not improve. These studies illustrate that the in vitro cytolytic properties of OVs are poor prognostic indicators of in vivo antitumor activity, and underscore the importance of adaptive antiviral CD8+ cytotoxic T-cells in effective cancer virotherapy.
Streptokinase and the Guillain-Barré Syndrome
Authors: DAVID A. LEAF
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 April 1984Streptokinase and the Guillain-Barré SyndromeDAVID A. LEAF, M.D., IAN MACDONALD, M.D., BERNARD KLIKS, M.D., REED WILSON, M.D., STEPHEN R. JONES, M.D.DAVID A. LEAF, M.D., IAN MACDONALD, M.D., BERNARD KLIKS, M.D., REED WILSON, M.D., STEPHEN R. JONES, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-4-617_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Guillain-Barré syndrome has been associated with infection, vaccination, malignancy, surgery, and pregnancy and has recently been reported in two patients who had received streptokinase (1, 2). We report the case of a third such patient.A 65-year-old man was awakened from sleep by acute chest pain. He had a history of coronary artery disease, and because of electrocardiographic changes, he was believed to have a developing acute inferior myocardial infarction. Immediate angiographic examination showed an occluded right coronary artery that failed to open after intra-coronary infusion of 80 000 units of streptokinase. Over the next 2...References1. EDEN K. Possible association of Guillain-Barré syndrome with thrombolytic therapy [Letter]. JAMA. 1983;249:2020-1. CrossrefMedlineGoogle Scholar2. SCHOENBERG B. Epidemiology of Guillain-Barré syndrome. Adv Neurol 1978;19:249-60. MedlineGoogle Scholar3. Notes from NINCDS: criteria established for Guillain-Barré diagnosis. Arch Neurol. 1978;35:623-4. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Good Samaritan Hospital Medical Center Portland, OR 97210 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDrug-Induced Guillain-Barré SyndromeThrombolytic agentsANTICOAGULANTS, THROMBOLYTIC AGENTS, AND ANTI-PLATELET DRUGSThrombolytic agentsDrug-Associated Guillain-Barré Syndrome: A Literature ReviewGuillain‐Barré syndrome complicating treatment with streptokinaseDrug Information Analysis ServiceThrombolytic retreatment with tissue plasminogen activator for threatened reinfarction and thrombotic coronary reocclusionRhabdomyolysis due to combined treatment with lovastatin and cholestyramine.Nifedipine induced gingival abscesses.Guillain-Barre syndrome after treatment with streptokinase.Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.Guillain-Barré therapy syndrome after streptokinaseAdverse Reactions to Thrombolytic AgentsDrugs affecting blood coagulation and hemostasisStreptokinase and the Guillain-Barré SyndromeJANET B. ARROWSMITH, M.D., JULIE B. MILSTIEN, Ph.D., JOEL N. KURITSKY, M.D., GENESIO MURANO, Ph.D. 1 April 1984Volume 100, Issue 4Page: 617-617KeywordsElectrocardiographyGuillain-Barre syndromeIschemiaMyocardial infarctionPregnancyRight coronary arterySleepStable coronary artery diseaseStreptococcal infectionsSurgery Issue Published: 1 April 1984 PDF DownloadLoading ...
Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study
Authors: Sajin Bae, Cornelia M. Ulrich, Marian L. Neuhouser, Olga Malysheva, Lynn B. Bailey, Liren Xiao, Elissa C. Brown, Kara L. Cushing-Haugen, Yingye Zheng, Ting-Yuan David Cheng, Joshua W. Miller, Ralph Green, Dorothy S. Lane, Shirley A.A. Beresford, Marie A. Caudill
Journal: Cancer Research (2014)

Abstract Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer risk among postmenopausal women in a case–control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case–control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)highest vs. lowest quartile = 2.44 (0.93–6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer overall [0.68 (0.47–0.99); P trend = 0.01] and with local/regional tumors [0.64 (0.42–0.99); P trend = 0.009]. Notably, the plasma betaine:choline ratio was inversely associated with colorectal cancer overall [0.56 (0.39–0.82); P trend = 0.004] as well as with proximal [0.66 (0.41–1.06); P trend = 0.049], rectal [0.27 (0.10–0.78); P trend = 0.02], and local/regional [0.50 (0.33–0.76); P trend = 0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25–9.16); P trend = 0.02] and with overall colorectal cancer risk among women with lower (vs. higher) plasma vitamin B12 levels (P interaction = 0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of colorectal cancer. The positive association between plasma TMAO and colorectal cancer risk is consistent with an involvement of the gut microbiome in colorectal cancer pathogenesis. Cancer Res; 74(24); 7442–52. ©2014 AACR.
Correction: Frequency of Antibodies to Hepatitis C Virus in Hepatocellular Carcinoma
Authors: Victor Vargas
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 June 1990Correction: Frequency of Antibodies to Hepatitis C Virus in Hepatocellular CarcinomaVictor Vargas, MDVictor Vargas, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-12-967_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:There are errors in the fifth paragraph of our letter (1). After the first sentence, the rest of the paragraph should read as follows: "Of 41 patients with hepatocellular carcinoma who had been transfused, 22 (54%) were anti-HCV positive, whereas of 40 patients who had not been transfused, 22 (55%) were anti-HCV positive (P= not significant). Twenty-five of thirty-eight (66%) patients with hepatocellular carcinoma who were anti-HBc positive compared with 19 of 43 (44%) patients with hepatocellular carcinoma and without anti-HBc were anti-HCV positive (P= not significant)."...Reference1. VargasCastellsEsteban VLJ. High frequency of antibodies to the hepatitis C virus among patients with hepatocellular carcinoma [Letter]. Ann Intern Med. 1990;112:232-3. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hospital Vall d'Hebron Universitat Autónoma Barcelona Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma 15 June 1990Volume 112, Issue 12Page: 967-967KeywordsAntibodiesHepatitis C virusHepatocellular carcinoma Issue Published: 15 June 1990 PDF downloadLoading ...
The Costs of Poor Health Habits
Authors: Luis G. Guerra
Journal: JAMA (1992)

For those who have idly wondered, while making ward rounds and seeing a patient with alcoholic cirrhosis and hepatic coma, what the cost to society is for heavy drinking—or, for that matter, for smoking or a sedentary life—the authors of this book provide answers. You might discover more than you care to know. Internal costs—individuals' lost wages, partial medical costs, disability, and premature death—are not the issue. Instead, the authors calculate the external costs, that is, the price individuals without these habits have to pay to subsidize those with unhealthy habits. Smokers, it turns out, not only have a reduced life expectancy compared with nonsmokers, but also pay 7 cents per pack more of out-of-pocket medical costs and lose 86 cents in wages and salaries. The external cost of smoking (ie, the cost to society) is about 15 cents per pack of cigarettes. The lifetime external cost of heavy drinking