tbuckley/cabot-search huggingface dataset:
Tissue Plasminogen Activator for Acute Ischemic Stroke
Authors: The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group
Journal: New England Journal of Medicine (1995)

Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials. We performed a randomized, double-blind trial of intravenous recombinant tissue plasminogen activator (t-PA) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke.
Abnormalities of cAMP-dependent endogenous phosphorylation in platelets from patients with bipolar disorder
Authors: J Perez, R Zanardi, S Mori, M Gasperini, E Smeraldi, G Racagni
Journal: American Journal of Psychiatry (1995)

The aim of the study was to assess cAMP-dependent endogenous phosphorylation in platelets from euthymic bipolar patients.Platelets from 10 drug-free euthymic patients with bipolar disorder were compared with those from 10 age- and sex-matched healthy subjects. Basal and cAMP-stimulated protein phosphorylation was examined in each group.Endogenous phosphorylation in both the healthy volunteers and the bipolar patients was significantly stimulated by cAMP; the major polypeptides had apparent molecular weights of 38 and 22 kDa. The cAMP-stimulated 32P incorporation differed between the bipolar patients and the comparison subjects only in the 22-kDa band.These data suggest a possible role of cAMP-dependent protein phosphorylation in the pathophysiology of bipolar disorder.
Mammographic Patterns and Breast Cancer Risk: Methodologic Standards and Contradictory Results
Authors: Norman F. Boyd, F.R.C.P. (C)
 3, Brian O'Sullivan, M.R.C.P. (I), Eve Fishell, F.R.C.P. (C), Imre Simor, F.R.C.P. (C), Gabriel Cooke, F.R.C.P. (C)
Journal: JNCI Journal of the National Cancer Institute (1984)

The claim that classification of the pattern of the breast parenchyma upon mammography can distinguish groups at different risks for breast cancer has been examined by 17 other studies published in the English language literature with contradictory results; this controversy was assessed by us in examination of these studies for their adherence to commonly accepted methodologic standards for the investigation of causal relationships. The nine standards for the examination of the studies included a description of the way the study population had been assembled and followed up and descriptions of the methods of mammographic pattern classification and breast cancer risk analysis. A strong association was found between the standards adopted by a study and the obtained results. Among nine cohort and case-control studies that found a statistically significant association between mammographic pattern and breast cancer risk, all met at least four standards, whereas only two of six "negative" cohort or case-control studies met as many as four standards. Among prevalence surveys, the association between methods and results was less striking, but several negative prevalence surveys were associated with "positive" cohort studies employing the same group of patients. These results indicate that methodologic differences among studies contribute substantially to the controversy surrounding this subject. Studies that follow the usual scientific methods employed in the epidemiologic investigation of risk generally have confirmed an association between mammographic pattern and breast cancer risk.
Notch signalling in human basophils
Authors: Katharina Cima, Gabriele Gamerith, Arno Amann, Christian M. Kähler, Judith Löffler-Ragg
Journal: European Respiratory Journal (2013)

Notch signalling plays a key role in the development of the immune system. Recently, Notch was found to induce lung allergic responsiveness in CD4+ T-cells and regulate eosinophil function. As basophils play a key role in allergic reactions, our aim was to analyse, whether basophils express Notch-1 or Notch-2 and whether Notch signaling has an impact on basophil function.  Human basophils were isolated from venous blood of healthy donors via magnetic cell sorting (MACS®). RNA and protein of basophils and PBMC were extracted. Notch-1 and Notch-2 expression was determined by RT-PCR and Western Blot. To explore Notch functionality, basophil migration towards Jagged-1 [10 -4  – 10 -14  M] and fMLP [10 -8  M] was evaluated in Boyden chambers. In a second setting basophils migrated towards fMLP [10 -8  M] after preincubation with the specific gamma secretase inhibitor DAPT [10 -6  – 10 -12  M]. Migration depth was analysed by microscopy. Furthermore, basophils were stimulated with plate-bound Jagged-1 for 24 h before histamine release was measured by ELISA.  The RT-PCR and Western Blots revealed basophils to express both, Notch-1 and Notch-2. In comparison to PBMC, human basophils were found to express Notch-1 to a greater extent, whereas Notch-2 expression was lower than that in PBMC. With regards to functionality we found that Jagged-1 [10 -8  M] most significantly induced chemotaxis in basophils and DAPT [10 -6  - 10 -8  M] most effectively blocked basophil migration (p
P163 Outcomes from a novel nurse led telephone clinic post thoracic surgery
Authors: A Hyde, A Moore, J Love, S Berwick, RA Thomas
Journal: Thorax (2015)

<h3>Background</h3> Moore <i>et al</i>.<sup>1</sup> reported that nurse led initiatives can reconfigure care, making it more responsive to individual needs, increasing patient satisfaction and reducing hospital visits. Nurse-led telephone follow up clinics post surgery have evidence of patient satisfaction and reduction in post-op complications,<sup>2</sup> but this is not a routine intervention post thoracic surgery. Prior to establishing our clinic, patients were discharged after thoracic surgery with a surgical outpatient appointment at 6 weeks and no routine community follow up. These patients had often undergone complicated surgery, and been discharged with chest drains or on strong opioids. <h3>Methods</h3> All patients discharged after surgery were contacted by telephone up to a maximum of a week after discharge with a further follow up call 2 weeks later if needed. A protocol of open questions was used to identify post-op difficulties at an early stage, facilitate referral to community teams, improve patient experience and provide additional information. <h3>Results and conclusion</h3> 29 patients were contacted over a 6 month period, following discharge after thoracic surgery; VATs, lobectomy, sleeve/wedge resection, pneumonectomy and pleurectomy. Each call lasted up to 20 min, equating to a maximum 10 h of nurse time. Telephone clinic highlighted a number of medical issues that required intervention and prevented GP and hospital appointments/admissions. Commonly reported symptoms included pain, shortness of breath, fatigue, constipation, weight loss and inability to sleep. In most cases simple advice and reassurance could be given. In 3 cases, medication was organised (antibiotics, laxatives, analgesia). A referral to the GP or community services was organised in 4 cases. Patient satisfaction was high however further evaluation over a longer period is needed. Additional study is necessary to explore the cost implications and the monetary value of avoiding admissions. <h3>References</h3> 1 Moore S, Corner J, Haviland J, <i>et al</i>. Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial. <i>BMJ</i> 2002;<b>325</b>:1145 2 Young JM, Butow PN, Walsh J, <i>et al</i>. Multicenter randomized trial of centralized nurse-led telephone-based care coordination to improve outcomes after surgical resection for colorectal cancer: The CONNECT intervention. <i>J Clin Oncol</i>. 2013;<b>31</b>:3585–91
Separation of Cells Containing R-Type Virus-Like Particles From a Simian Virus 40-lnduced Hamster Tumor Cell Line23
Authors: D. G. Bergman, J. R. Blakeslee, D.w A. Wolff
Journal: JNCI Journal of the National Cancer Institute (1977)

Cells derived from a simian virus 40-induced hamster fibrosarcoma were separated into two distinct cell bands of differing buoyant densities. The lighter cell band or fraction (F1) had a buoyant density range of 1.025-1.032 g/ml and comprised 3.8% of the total cells applied to the gradient, whereas the heavier cell fraction (F2) had a buoyant density range of 1.054-1.074 g/ml and comprised 95.3% of the total cells applied. Both cell fractions were tumorigenic and did not differ greatly in cell type, viability, mitotic index, or their ability to incorporate [3H]thymidine. However, ultrastructurally, the F1 cells contained R-type virus-like particles within dilated intracisternal spaces and exhibited cytoplasmic vacuoles. In the F2 cells, few detectable R-type particles and cytoplasmic vacuoles were revealed by electron microscopy. The F2 cells demonstrated a twofold greater ability to incorporate [14C]protein hydrolysate into proteins than did the F1 cells.
Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis
Authors: Shadmehr Demehri, Trevor J. Cunningham, Sindhu Manivasagam, Kenneth H. Ngo, Sara Moradi Tuchayi, Rasika Reddy, Melissa A. Meyers, David G. DeNardo, Wayne M. Yokoyama
Journal: Journal of Clinical Investigation (2016)

Advances in the field of cancer immunology, including studies on tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, CD4+ Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers.
PTU-251 Emergency laparotomy survival factors in a unique 100%- consultant operator series
Authors: S Brown, C Ray, J Edwards, N French, SJ Moug
Journal: Gut (2015)

<h3>Introduction</h3> There is increasing interest in assessing outcomes from emergency laparotomy in the UK, and implementing care bundles to improve them. This follows on from work from the National Emergency Laparotomy Network suggesting that laparotomy mortality rates are at a level that would be ‘unthinkable’ from elective surgery (average 14.9% mortality). It noted variability in presence of consultant surgeons and anaesthetists at the surgery and related this to possible variations in mortality. In the knowledge that consultant presence at laparotomy is extremely high at our busy District General Hospital, research was carried out into the factors influencing the survival of the emergency laparotomy patients. <h3>Method</h3> A prospective database was created of 144 consecutive laparotomy patients, using local hospital and NELA data. The following factors were ascertained: grade of surgeon and anaesthetist, deprivation score, day of week of surgery, time of day of surgery, ASA grade, postoperative P-POSSUM predicted mortality (combining operative severity score and preoperative physiology), length of stay, 30-day mortality. Survival was ascertained using Kaplan-Meier analysis, with univariate analysis by log-rank test and then multivariate analysis performed using Cox Proportional Hazards Analysis. <h3>Results</h3> 100% of patients were operated on by consultant surgeons and 95% had a consultant anaesthetist presence. The 30-day mortality rate seen overall was 17.4%. It was notable that the mean P-POSSUM score for the patients was 17.2%. 50% were aged over 65. Of note even on univariate analysis, time of day of operation and weekday versus weekend were not significant predictors of mortality. On multivariate analysis, P-POSSUM score, ASA grade and age remained independent predictors of emergency laparotomy mortality. <h3>Conclusion</h3> Even in a series of patients operated on exclusively by consultants, mortality is close to the national average. It is likely that strong influences on this are the severity of patient physiology and severity of operation, seen in the striking similarity of mean P-POSSUM and observed mortality in these patients, and its independence on multivariate analysis. As expected, age is also an independent factor. Further work will be carried out to see if any remediable factors could be contributing. <h3>Disclosure of interest</h3> None Declared.
Specific Binding of Factor(s) Released by Rous Sarcoma Virus-Transformed Cells to Splenocytes of Chickens With Rous Sarcomas2
Authors: Z. Ben-Sasson, D. W. Weiss, F. Doljanski
Journal: JNCI Journal of the National Cancer Institute (1974)

Normal and Rous sarcoma virus (RSV}-transformed chicken embryo cells shed molecules, presumably macromolecular membrane constituents, that contain glucosamine and choline into their culture media. Such molecules from RSV-transformed cells are bound preferentially to spleen cells from chickens bearing RSV-induced sarcomas. These lymphoid cells do not preferentially adsorb analogous labeled molecules from normal chicken embryo or from a variety of other normal and neoplastic cell cultures, except those of cells transformed by viruses of the avian leukosis sarcoma complex. Specific binding is not abrogated by inactivation of the lymphoid cells with azide or cyanide. The possible biologic implications of these findings are discussed.
Growth Inhibition of a Human Myeloma Cell Line by All-transRetinoic Acid Is Not Mediated Through Downregulation of Interleukin-6 Receptors but Through Upregulation of p21WAF1
Authors: Yi-Hsiang Chen, Donald Lavelle, Joseph DeSimone, Shahab Uddin, Leonidas C. Platanias, Maria Hankewych
Journal: Blood (1999)
Radioprotective Agents: Strategies and Translational Advances
Authors: Mohammad Zahid Kamran, Atul Ranjan, Navrinder Kaur, Souvik Sur, Vibha Tandon
Journal: Medicinal Research Reviews (2016)

Abstract Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed.
Halfway There? Health Reform Starts Now
Authors: Risa Lavizzo-Mourey
Journal: JAMA (2016)

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Trihalomethanes in Drinking Water and Human Colorectal Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C E Lawrence, P R Taylor, B J Trock, A A Reilly
Journal: JNCI Journal of the National Cancer Institute (1984)

The relation of trihalomethanes (THM) to colorectal cancer was evaluated. A total of 395 colorectal cancer deaths among white women teachers in New York State was compared to an equal number of deaths of teachers from noncancerous causes. Cumulative chloroform (CHCI3) exposure was estimated by the application of a statistical model to operational records from the individual water treatment facilities that served the home and work addresses of each study subject during the 20 years prior to death. The odds of exposure to a surface source containing little or no THM was no greater for cases than for controls. The odds ratio=1.07; the 90% confidence interval=0.79–1.43; and the P=.68. The distribution of CHCI3 exposure was not significantly different between cases and controls (rated by Wilcoxon signed rank statistic=-0.52; P=.60). No effect of cumulative CHCI3 exposure on outcome was seen in a logistic analysis controlling for average source type, population density, marital status, age, and year of death (likelihood ratio test statistic=0.047; P=.83).
The relation between air pollution and respiratory tract diseases by months in Duzce City of Turkey
Authors: Ege Gulec Balbay, Oner Balbay, Peri Arbak, Ali Nihat Annakkaya
Journal: European Respiratory Journal (2011)

Aim:  To investigate the relationship between levels of particulate matter (PM 10 ) and sulphur dioxide (SO 2 ) and the patients with COPD, asthma, respiratory tract infection (respiratory tract disease-RTD) applied to policlinics in the central part and counties of Duzce.   Material:  Between 1 January 2009 and 31 December 2009 in Duzce Ataturk State Hospital, the patients diagnosed as RTD at chest, internal medicine, ENT, pediatric polyclinics were retrospectively evaluated. The monthly average values of SO 2  and PM 10  obtained from the official data of Ministry of Environment and Forests.   Results:  53.1% of 29,367 cases were female. 64.4% of cases were adults. The average SO 2  and PM 10  concentration was highest in November, December, January and those were the lowest in July, August, September and October. Acute bronchitis were higher than the remaining in January (26.9%) and December (25.4%), while those were the lowest in July 16.4%) and September (20.4%), respectively. COPD were more frequent in January (10%), February (10.9%), March (13.1%), but less in September (5.9%). Asthma were most admitted in December (10.6%), January (9.6%) but less frequently in September (6.1%). Pneumonia were frequently admitted in November (10.6%), January (9.6%). The allergic rhinitis was the most common at the seaside (119/479, 24.8%) (p=0.000). Upper RTD (58%) were higher than the lower RTD in the months that the air pollution was the highest (p=0.000).   Conclusion:  It was speculated that polyclinics admissions of COPD, asthma, acute bronchitis, pneumonia seem to be associated with air pollution and also living in the seaside may lead to more increase in applications regarding allergic rhinitis.
Interferon and Cell Division. IX. Interferon-Resistant L1210 Cells: Characteristics and Origin2
Authors: Ion Gresser, Marie-Thérèse Bandu, Danièle Brouty-Boyé
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Interferon and Cell Division. IX. Interferon-Resistant L1210 Cells: Characteristics and Origin Get access Ion Gresser, Ion Gresser Search for other works by this author on: Oxford Academic PubMed Google Scholar Marie-Thérèse Bandu, Marie-Thérèse Bandu Search for other works by this author on: Oxford Academic PubMed Google Scholar Danièle Brouty-Boyé Danièle Brouty-Boyé Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 553–559, https://doi.org/10.1093/jnci/52.2.553 Published: 01 February 1974 Article history Received: 13 July 1973 Accepted: 19 October 1973 Published: 01 February 1974
Finding a Human Leukocyte Antigen Match—A Perfect Stranger
Authors: Jacob Adashek
Journal: JAMA Internal Medicine (2016)

A perfect stranger saved my life. He didn’t jump in front of a moving vehicle or fend off an attacker. He wasn’t perfect for the reasons one might think, but for my predicament, he was indeed perfect—a 10 out of 10 match, to be exact. I required such a match to survive.
Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease
Authors: Frank Lezoualc’h, Loubina Fazal, Marion Laudette, Caroline Conte
Journal: Circulation Research (2016)

cAMP is a universal second messenger that plays central roles in cardiovascular regulation influencing gene expression, cell morphology, and function. A crucial step toward a better understanding of cAMP signaling came 18 years ago with the discovery of the exchange protein directly activated by cAMP (EPAC). The 2 EPAC isoforms, EPAC1 and EPAC2, are guanine-nucleotide exchange factors for the Ras-like GTPases, Rap1 and Rap2, which they activate independently of the classical effector of cAMP, protein kinase A. With the development of EPAC pharmacological modulators, many reports in the literature have demonstrated the critical role of EPAC in the regulation of various cAMP-dependent cardiovascular functions, such as calcium handling and vascular tone. EPAC proteins are coupled to a multitude of effectors into distinct subcellular compartments because of their multidomain architecture. These novel cAMP sensors are not only at the crossroads of different physiological processes but also may represent attractive therapeutic targets for the treatment of several cardiovascular disorders, including cardiac arrhythmia and heart failure.