tbuckley/cabot-search huggingface dataset:
Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial
Authors: Guy L Clifton, Alex Valadka, David Zygun, Christopher S Coffey, Pamala Drever, Sierra Fourwinds, L Scott Janis, Elizabeth Wilde, Pauline Taylor, Kathy Harshman, Adam Conley, Ava Puccio, Harvey S Levin, Stephen R McCauley, Richard D Bucholz, Kenneth R Smith, John H Schmidt, James N Scott, Howard Yonas, David O Okonkwo
Journal: The Lancet Neurology (2010)
Predictors of Biochemical Outcome With Salvage Conformal Radiotherapy After Radical Prostatectomy for Prostate Cancer
Authors: Matthew S. Katz, Michael J. Zelefsky, Ennapadam S. Venkatraman, Zvi Fuks, Amanda Hummer, Steven A. Leibel
Journal: Journal of Clinical Oncology (2003)

Purpose: To identify predictors of biochemical outcome following radiotherapy in patients with a rising prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer. Patients and Methods: One hundred fifteen patients with a rising PSA after radical prostatectomy received salvage three-dimensional conformal radiotherapy (3D-CRT) alone or with neoadjuvant androgen deprivation. Tumor-related and treatment-related factors were evaluated to identify predictors of subsequent PSA failure. Results: The median follow-up time after 3D-CRT was 42 months. The 4-year actuarial PSA relapse-free survival, distant metastasis-free survival, and overall survival rates were 46%, 83%, and 95%, respectively. Multivariate analysis, which was limited to 70 patients receiving radiation without androgen deprivation therapy, showed that negative/close margins (P = .03), absence of extracapsular extension (P &lt; .01), and presence of seminal vesicle invasion (P &lt; .01) were independent predictors of PSA relapse after radiotherapy. Neoadjuvant androgen deprivation did not improve the 4-year PSA relapse-free survival in patients with positive margins, extracapsular extension, and no seminal vesicle invasion (P = .24). However, neoadjuvant androgen deprivation did improve PSA relapse-free survival when one or more of these variables were absent (P = .03). Conclusions: Salvage 3D-CRT can provide biochemical control in selected patients with a rising PSA after radical prostatectomy. Among patients with positive margins and no poor prognostic features, 77% achieved PSA control after salvage 3D-CRT. Salvage neoadjuvant androgen deprivation therapy may improve short-term biochemical control, but it requires further study.
Studies of Paroxysmal Nocturnal Hemoglobinuria Erythrocytes: Increased Lysis and Lipid Peroxide Formation by Hydrogen Peroxide*
Authors: Charles E. Mengel, Herbert E. Kann, Wilhelm D. Meriwether
Journal: Journal of Clinical Investigation (1967)

When paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes were exposed to H(2)O(2) they lysed excessively and formed greater than normal quantities of lipid peroxides when compared to red cells of normal subjects and patients with most types of hematologic disease. It was also shown that lytic sensitivity to acidified serum was related to the enhanced lytic sensitivity to H(2)O(2). If the lipid of PNH cells was first extracted then exposed to ultraviolet radiation more lipid peroxides were formed than in extracts of normal red blood cells. The possible explanations for these findings and their relationship to the PNH hemolytic mechanism are discussed.
Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis
Authors: Despina S Kyriakou, Michael G Alexandrakis, Kalliopi Zachou, Freda Passam, Nikolaos E Stathakis, Georgios N Dalekos
Journal: Journal of Hepatology (2003)
Genome-wide association analysis reveals 12q13.3–q14.1 as new risk locus for sarcoidosis
Authors: Sylvia Hofmann, Annegret Fischer, Michael Nothnagel, Gunnar Jacobs, Benjamin Schmid, Michael Wittig, Andre Franke, Karoline I. Gaede, Manfred Schürmann, Martin Petrek, Frantisek Mrazek, Stefan Pabst, Christian Grohé, Johan Grunewald, Marcus Ronninger, Anders Eklund, Philip Rosenstiel, Kerstin Höhne, Gernot Zissel, Joachim Müller-Quernheim, Stefan Schreiber
Journal: European Respiratory Journal (2012)

Sarcoidosis is a systemic inflammatory disease of unknown aetiology, influenced by genetic and environmental factors. However, the loci so far identified for sarcoidosis explain only a part of its assumed heritability. To identify further susceptibility loci, we performed a genome-wide association analysis using the Affymetrix 6.0 Human GeneChip followed by validation and replication stages. After quality control, 637 cases, 1233 controls and 677 619 single-nucleotide polymorphisms (SNPs) were available for an initial screening. 99 SNPs were selected for validation in an independent study panel (1664 patients, 2932 controls). SNP rs1050045 was significantly associated with sarcoidosis (corrected p=0.0215) in the validation panel and yielded a p-value of 9.22 × 10(-8) (OR 1.24) in the meta-analysis of the screening and validation stage. A meta-analysis of three populations from Germany, the Czech Republic and Sweden confirmed this finding (p = 0.024; OR 1.14). Fine-mapping and mRNA expression studies pointed to osteosarcoma amplified 9 (OS9) as the most likely candidate for the underlying risk factor. The OS9 protein plays an important role in endoplasmic reticulum-associated protein degradation and acts during Toll-like receptor induced activation of myeloid cells. Expression analyses of OS9 mRNA provide evidence for a functional mechanism underlying the detected association signal.
Screening Data from the Cancer Chemotherapy National Service Center Screening Laboratories. XXIII
Authors: Joseph Leiter, B. J. Abbott, Saul A. Schepartz
Journal: Cancer Research (1965)

Abstract  Data are reported on 2,081 synthetic compounds which were tested in the CCNSC primary screens. Almost all of the compounds were tested in Sarcoma 180, Carcinoma 755, Leukemia 1210, and KB cells in culture; some tests were also carried out in Friend virus leukemia and Lewis lung carcinoma. Data are reported only on compounds which have not demonstrated sufficient activity in these systems to warrant further investigation.
Fibro-Sanguineous Tumor of the Dura Mater
Authors: T. N. Day
Journal: BMJ (1842)

FIBRO-SANGUINEOUS TUMOR OF DURA MATER.187 mixture, with laudanum, was prescribed to allay any bronchial irritation that might arise.19.She had some pain in the left eye during yes- terday and last night, but it had much abated this morning; there was also some discharge of water from this eye yesterday afternoon, but this too had ceased.The right eye had been very easy.She did not sleep much, but was not teazed with coughing during the night.The dressings were not removed.20.The patient was much the same as yesterday.
The B cell-specific transcription factor BSAP regulates B cell proliferation.
Authors: Y Wakatsuki, M F Neurath, E E Max, W Strober
Journal: The Journal of Experimental Medicine (1994)

The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In this study, we explored the role of BSAP in B cell function by assessing how the content of this protein varies in cells driven by proliferative stimuli and, conversely, how artificial manipulation of BSAP activity affects cell proliferation. We found that BSAP activity of nuclear extracts increased when B cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor-mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell-dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP translation initiation start site, whereas control oligonucleotides were virtually inactive. Antisense-induced BSAP suppression was associated with a striking reduction in LPS-induced proliferation of splenic B cells and in the spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense oligonucleotide had virtually no effect on proliferation of two cell lines lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315. Overexpression of BSAP in splenic B cells or de novo expression in MOPC-315 plasma cells induced by transfection of a BSAP expression plasmid stimulated cell proliferation. Taken together, these results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation. We also found that treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or could be mediated through BSAP binding sites in the IgH locus.
Incidence and clinical relevance of uncontrolled ventricular rate during atrial fibrillation in heart failure patients treated with cardiac resynchronization therapy
Authors: Giuseppe Boriani, Maurizio Gasparini, Maurizio Landolina, Maurizio Lunati, Alessandro Proclemer, Gabriele Lonardi, Saverio Iacopino, Werner Rahue, Mauro Biffi, Paola DiStefano, Andrea Grammatico, Massimo Santini
Journal: European Journal of Heart Failure (2011)
OBSERVATIONS ON BLOOD REACTION IN EXPERIMENTAL PNEUMONIA
Authors: Chauncey D. Leake, J. L. Vickers, Thomas K. Brown
Journal: The Journal of Experimental Medicine (1924)

The correlation of the lung lesions and anemia in dogs suffering from experimental pneumonia induced by various organisms, with changes in the respiratory activity and in the acid-base relationship in blood, indicates that the developing acidosis, most marked in the severe cases, is due chiefly to the effects of an anoxic anoxemia.
Laparotomy Versus No Laparotomy in the Management of Early-Stage, Favorable-Prognosis Hodgkin's Disease: A Decision Analysis
Authors: Andrea K. Ng, Jane C. Weeks, Peter M. Mauch, Karen M. Kuntz
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. METHODS: We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. RESULTS: The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging. The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. CONCLUSION: Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. These results suggest that a role remains for surgical staging in the management of early-stage HD.
Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men
Authors: Peter L. Anderson, David V. Glidden, Albert Liu, Susan Buchbinder, Javier R. Lama, Juan Vicente Guanira, Vanessa McMahan, Lane R. Bushman, Martín Casapía, Orlando Montoya-Herrera, Valdilea G. Veloso, Kenneth H. Mayer, Suwat Chariyalertsak, Mauro Schechter, Linda-Gail Bekker, Esper Georges Kallás, Robert M. Grant
Journal: Science Translational Medicine (2012)

PrEP drug concentrations associated with ≥90% reduction in HIV acquisition in men who have sex with men are achieved with daily dosing.
Pathogenesis of Exercise-Induced Asthma: Implications for Treatment
Authors: J R Haltom, R C Strunk
Journal: Annual Review of Medicine (1986)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Prognostic value of weight change in chronic obstructive pulmonary disease: results from the Copenhagen City Heart Study
Authors: E. Prescott, T. Almdal, K.L. Mikkelsen, C.L. Tofteng, J. Vestbo, P. Lange
Journal: European Respiratory Journal (2002)

An association between low body mass index (BMI) and poor prognosis in patients with chronic obstructive pulmonary disease (COPD) has been found in a number of studies. The prevalence and prognostic importance of weight change in unselected subjects with COPD was examined. Subjects with COPD, defined as forced expiratory volume in one second/forced vital capacity &lt;0.7 in the Copenhagen City Heart Study and who attended two examinations 5 yrs apart, were followed for 14 yrs for COPD-related and all-cause mortality. The proportion of subjects who lost &gt;1 unit BMI (∼3.8 kg) between the two examinations was significantly associated with level of COPD, reaching ∼30% in subjects with severe COPD. After adjusting for age, smoking habits, baseline BMI and lung function, weight loss was associated with higher mortality in both persons with and without COPD (rate ratio (RR) for weight loss &gt;3 BMI units 1.71 (95% confidence interval (CI): 1.32–2.23) and 1.63 (95% CI 1.38–1.92), respectively). Weight gain was associated with increased mortality, but not significantly so in subjects with COPD. Risk of COPD-related death increased with weight loss (RR 2.14 (95% CI 1.18–3.89)), but not with weight gain (RR 0.95 (95% CI 0.43–2.08)). In subjects without COPD or with mild-to-moderate COPD, the effect of weight change was the same irrespective of initial weight. In subjects with severe COPD, there was a significant risk ratio modification (p=0.045) between effect of baseline BMI and weight change: in the normal-to-underweight (BMI&lt;25), best survival was seen in those who gained weight, whereas for the overweight and obese (BMI≥25), best survival was seen in stable weight. A high proportion of subjects with chronic obstructive pulmonary disease experienced a significant weight loss, which was associated with increased mortality. The results support further intervention studies that aim at avoiding weight loss in normal-to-underweight chronic obstructive pulmonary disease patients.
Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions
Authors: C P Denton
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication of CTD is pulmonary arterial hypertension (PAH), which has a major effect on functioning and quality of life, and is associated with a particularly poor prognosis. <b>Objective:</b> To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD, mostly SSc and lupus erythematosus. <b>Methods:</b> 66 patients with PAH secondary to CTD, in World Health Organization functional class III or IV, were randomised to two double-blind, placebo-controlled studies and followed up for 12 and 16 weeks, respectively. The primary end point was change in exercise capacity, assessed using the 6-min walk test. In both studies and their extensions, survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan–Meier estimates. <b>Results:</b> 44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study (+19.5 m, 95% confidence interval (CI) −3.2 to 42.2), whereas patients treated with placebo deteriorated (−2.6 m, 95% CI −54.0 to 48.7). 64 patients subsequently received bosentan in an open-label long-term extension study. Mean (standard deviation (SD)) exposure to bosentan was 1.6 (0.9) years, and duration of observation was 1.8 (0.8) years. 8 (16%) patients received epoprostenol as add-on treatment and 7 (14%) after discontinuation of bosentan. Survival in those receiving bosentan was 85.9% after 1 year and 73.4% after 2 years. <b>Conclusion:</b> Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo. The long-term follow-up of these patients suggests that first-line bosentan, with the subsequent addition of other PAH treatments if required, is safe for long-term treatment and may have a positive effect on outcome.
In Vivo Interactions Between H2-Receptor Antagonists and Ethanol Metabolism in Man and in Rats
Authors: Helmut K. Seitz, Siegrid Veith, Peter Czygan, Johann Bösche, Bernd Simon, Roland Gugler, Burkhard Kommerell
Journal: Hepatology (1984)

The influence of a 7-day medication of either cimetidine (1,000 mg per day) or ranitidine (300 mg per day) on serum ethanol concentrations after a single oral dose of ethanol (0.8 gm per kg body weight) was investigated in a randomized placebo-controlled study in eight male volunteers. Compared with the placebo, cimetidine but not ranitidine produced a significant increase in both the peak serum ethanol concentration (85.9 ± 3.5 vs. 73.0 ± 3.2 mg dl −1 , p &lt; 0.02) and in the area under the serum ethanol concentration time curve (350 ± 19 vs. 304 ± 25 mg dl −1 hr −1 , p &lt; 0.05). However, the ethanol elimination rate was not affected by cimetidine. When ethanol (1.0 gm per kg body weight) was administered intravenously, cimetidine failed to induce a change in ethanol metabolism. Furthermore, the effect of H 2 -receptor antagonists was studied in animal experiments. Female Sprague-Dawley rats received a single dose of ethanol (7 or 3 gm per kg body weight) together with an intraperitoneal injection of either cimetidine (120 mg per kg body weight), ranitidine (120 mg per kg body weight) or isotonic saline. After alcohol absorption, ethanol elimination was significantly inhibited by both cimetidine (3.99 ± 0.39 vs. 5.68 ± 0.23 mmoles kg −1 hr −1 , p &lt; 0.02) and ranitidine (4.21 ± 0.14 vs. 5.68 ± 0.23 mmoles kg −1 hr −1 , p &lt; 0.02) at high ethanol concentrations (60 to 20 m M ) but not at blood ethanol concentrations below 20 m M . These results suggest an increase in ethanol absorption due to cimetidine but not to ranitidine in man at ethanol serum concentrations below 20 m M . At ethanol serum concentrations above 20 m M , both H 2 -receptor antagonists inhibit ethanol elimination in the rat suggesting inhibition of microsomal ethanol oxidation.
Excitatory effects of adrenaline upon isolated preparations of human colon
Authors: D. J. Gagnon, G. Devroede, S. Belisle
Journal: Gut (1972)

The effect of beta-adrenergic blockade with oxprenolol upon adrenaline-induced relaxation of strips of human sigmoid colon was investigated. Following blockade of beta-adrenoceptors with oxprenolol, adrenaline evoked dose-dependent contractions of both longitudinal and circular muscle strips. Storage of the tissues for periods up to 24 hours at 4 degrees C did not modify the responses to adrenaline. Furthermore, the contractions induced by adrenaline following oxprenolol were significantly diminished by the addition of phentolamine, an alpha-adrenoceptor blocking agent. Our results would suggest that oxprenolol has the property of unmasking or revealing alpha receptors responsible for the excitatory effects of adrenaline upon isolated strips of human colon.
Effects of Siltuximab on the IL-6–Induced Signaling Pathway in Ovarian Cancer
Authors: Yuqi Guo, Jeffrey Nemeth, Colin O'Brien, Michiro Susa, Xianzhe Liu, Zhan Zhang, Edwin Choy, Henry Mankin, Francis Hornicek, Zhenfeng Duan
Journal: Clinical Cancer Research (2010)

To explore potential therapeutic strategies for interrupting the interleukin-6 (IL-6) signaling pathway, we measured IL-6 expression in ovarian cancer tissues, and evaluated the effects of a monoclonal anti-IL-6 antibody; siltuximab (CNTO 328), on levels of IL-6-induced Stat3 phosphorylation, Stat3 nuclear translocation, and Stat3 downstream antiapoptotic genes. We then looked for enhancing paclitaxel sensitivity in multidrug-resistant ovarian cancer cell lines.Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry. Effects of siltuximab on IL-6-induced activation of Stat3 in an ovarian cancer cell line were determined by Western blot and real-time analysis of Stat3 nucleocytoplasmic translocation. Influence of combination of siltuximab and paclitaxel on tumor growth was evaluated in a xenograft mouse mode in vivo.Metastatic and drug-resistant recurrent tumors have significantly higher IL-6 expression when compared with the matched primary tumors. Siltuximab specifically suppressed IL-6-induced Stat3 phosphorylation and Stat3 nuclear translocation. Treatment with siltuximab significantly decreased the levels of Stat3 downstream proteins such as MCL-1, Bcl-X(L), and survivin. Treatment with siltuximab reduced expression of multiple IL-6-induced genes in these cell lines. Furthermore, siltuximab increased the cytotoxic effects of paclitaxel in a paclitaxel resistant ovarian cancer cell line in vitro, but combination therapy with siltuximab did not have a significant effect on paclitaxel resistant tumor growth in vivo.These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression. Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer.
Structure and Function of the p53 Tumor Suppressor Gene: Clues for Rational Cancer Therapeutic Strategies
Authors: C. C. Harris
Journal: JNCI Journal of the National Cancer Institute (1996)

The p53 tumor suppressor protein is involved in multiple central cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control, and apoptosis. p53 is functionally inactivated by structural mutations, interaction with viral products, and endogenous cellular mechanisms in the majority of human cancers. This functional inactivation can, in some circumstances, produce resistance to DNA-damaging agents commonly used in cancer chemotherapy and radiotherapeutic approaches. Current research is defining the biochemical pathways through which p53 induces cell cycle arrest and apoptosis. Knowledge of these fundamental processes is leading to the identification of molecular targets toward which multimodality cancer therapies, using chemotherapeutic, immunotherapeutic, and gene-therapeutic strategies, can be based.