tbuckley/cabot-search huggingface dataset:
OBSERVATIONS ON THE RELEASE OF SERUM FIBRINOLYSIN BY SPECIFIC ANTIGEN, PEPTONE, AND CERTAIN POLYSACCHARIDES
Authors: Georges Ungar, Shirley H. Mist
Journal: The Journal of Experimental Medicine (1949)

FORMATION OF FIBRINOLYSIN FROM ITS INACTIVE PRECURSOR IN SERUM WAS OBSERVED UNDER THE FOLLOWING CONDITIONS: (a) by adding the specific antigen to serum from sensitized guinea pigs; (b) by mixing normal guinea pig serum with peptone, agar, hyaluronic acid, chondroitinsulfuric acid, glycogen, pneumococcal polysaccharides, and heparin. Activation of profibrinolysin by these agents differs from chloroform or streptokinase activation in that it requires the presence of some serum constituent non-precipitable with the euglobulin fraction and destroyed by heating at 56 degrees C. The bearing of these observations on the mechanism of anaphylactic and anaphylactoid reactions is discussed. The findings reported support the concept that proteolysis is part of the process determining the release of histamine and other toxic products. It is suggested that the presence of fibrinokinase may be responsible for the toxicity of serum induced in vitro by a number of agents.
Relative Efficacy of Mindfulness-Based Relapse Prevention, Standard Relapse Prevention, and Treatment as Usual for Substance Use Disorders
Authors: Sarah Bowen, Katie Witkiewitz, Seema L. Clifasefi, Joel Grow, Neharika Chawla, Sharon H. Hsu, Haley A. Carroll, Erin Harrop, Susan E. Collins, M. Kathleen Lustyk, Mary E. Larimer
Journal: JAMA Psychiatry (2014)

Relapse is highly prevalent following substance abuse treatments, highlighting the need for improved aftercare interventions. Mindfulness-based relapse prevention (MBRP), a group-based psychosocial aftercare, integrates evidence-based practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches.To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual (TAU [12-step programming and psychoeducation]) during a 12-month follow-up period.Between October 2009 and July 2012, a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private, nonprofit treatment facility were randomized to MBRP, RP, or TAU aftercare and monitored for 12 months. Participants medically cleared for continuing care were aged 18 to 70 years; 71.5% were male and 42.1% were of ethnic/racial minority.Participants were randomly assigned to 8 weekly group sessions of MBRP, cognitive-behavioral RP, or TAU.Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days. Variables were assessed at baseline and at 3-, 6-, and 12-month follow-up points. Measures used included self-report of relapse and urinalysis drug and alcohol screenings.Compared with TAU, participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and, among those who used substances, significantly fewer days of substance use and heavy drinking at the 6-month follow-up. Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use. At the 12-month follow-up, MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU.For individuals in aftercare following initial treatment for substance use disorders, RP and MBRP, compared with TAU, produced significantly reduced relapse risk to drug use and heavy drinking. Relapse prevention delayed time to first drug use at 6-month follow-up, with MBRP and RP participants who used alcohol also reporting significantly fewer heavy drinking days compared with TAU participants. At 12-month follow-up, MBRP offered added benefit over RP and TAU in reducing drug use and heavy drinking. Targeted mindfulness practices may support long-term outcomes by strengthening the ability to monitor and skillfully cope with discomfort associated with craving or negative affect, thus supporting long-term outcomes.clinicaltrials.gov Identifier: NCT01159535
Chronic Kidney Disease After Nephrectomy in Patients with Small Renal Masses: A Retrospective Observational Analysis
Authors: Maxine Sun, Marco Bianchi, Jens Hansen, Quoc-Dien Trinh, Firas Abdollah, Zhe Tian, Jesse Sammon, Shahrokh F. Shariat, Markus Graefen, Francesco Montorsi, Paul Perrotte, Pierre I. Karakiewicz
Journal: European Urology (2012)
Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia
Authors: Raymond Ng, Heng Wu, Hong Xiao, Xin Chen, Holger Willenbring, Clifford J. Steer, Guisheng Song
Journal: Hepatology (2014)

The incidence of nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia, with their associated risks of endstage liver and cardiovascular diseases, is increasing rapidly due to the prevalence of obesity. Although the mechanisms of NAFLD have been studied extensively, the underlying pathogenesis and the role of microRNAs in this process remain relatively unclear. MicroRNA (miRNA)-dependent posttranscriptional gene silencing is now recognized as a key element of lipid metabolism. Here we report that the expression of microRNA-24 (miR-24) is significantly increased in the livers of high-fat diet-treated mice and in isolated human hepatocytes incubated with fatty acid. Knockdown of miR-24 in those mice caused impaired hepatic lipid accumulation and reduced plasma triglycerides. Bioinformatic and in vitro and in vivo studies led us to identify insulin-induced gene 1 (Insig1), an inhibitor of lipogenesis, as a novel target of miR-24. Inhibition of endogenous miR-24 expression by way of miR-24 inhibitors led to up-regulation of Insig1, and subsequently decreased hepatic lipid accumulation. It is well established that liver-specific deletion of Insig1 leads to higher hepatic and plasma triglyceride levels by inhibiting the processing of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate lipid synthesis. As expected, miR-24 knockdown prevented SREBP processing, and subsequent expression of lipogenic genes. In contrast, the opposite result was observed with overexpression of miR-24, which enhanced SREBP processing. Thus, our study defines a potentially critical role for deregulated expression of miR-24 in the development of fatty liver by way of targeting of Insig1. Our findings show a novel mechanism by which miR-24 promotes hepatic lipid accumulation and hyperlipidemia by repressing Insig1, and suggest the use of miR-24 inhibitor as a potential therapeutic agent for NAFLD and/or atherosclerosis.
Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease.
Authors: A Kukita, C Chenu, L M McManus, G R Mundy, G D Roodman
Journal: Journal of Clinical Investigation (1990)

Although Paget's disease is the most flagrant example of a primary osteoclast disorder, little is known of osteoclast biology in this disease. In this report we have studied the formation of cells with the osteoclast phenotype in long-term cultures of marrow mononuclear cells derived from patients with Paget's disease, and compared these with similar cells formed in long-term marrow cultures from normal individuals, and with osteoclasts present in pagetic bone. Osteoclasts formed in pagetic marrow cultures resembled osteoclasts present in pagetic bone, but were distinctly different from osteoclasts formed in normal marrow cultures. Osteoclast formation was 10-20-fold greater in pagetic marrow cultures than in normal cultures. The multinucleated cells formed in cultures of pagetic marrow were much larger in size, were hyperresponsive to 1,25(OH)2 vitamin D, had more nuclei per cell, had increased levels of tartrate-resistant acid phosphatase activity and had ultrastructural features which were not seen in multinucleated cells formed from normal marrow mononuclear cells. These pagetic marrow-derived multinucleated cells formed large resorption lacunae on calcified matrices and cross-reacted with monoclonal antibodies which preferentially bind to osteoclasts. The multinucleated cells formed from marrow obtained from uninvolved sites in Paget's patients also displayed these abnormal features.
Reply from Authors re: Giuseppe Morgia. Does the Use of Silodosin to Treat Benign Prostatic Hyperplasia Really Offer Something New? Eur Urol 2011;59:353–5
Authors: Christopher R. Chapple, Francesco Montorsi, Teuvo L.J. Tammela, Manfred Wirth, Evert Koldewijn, Eldiberto Fernández Fernández
Journal: European Urology (2010)
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Authors: Constantinos Petrovas, Joseph P. Casazza, Jason M. Brenchley, David A. Price, Emma Gostick, William C. Adams, Melissa L. Precopio, Timothy Schacker, Mario Roederer, Daniel C. Douek, Richard A. Koup
Journal: The Journal of Experimental Medicine (2006)

Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8+ T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8+ T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8+ T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8+ T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8+ T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo.
Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy.
Authors: A.T Casey, J.M Bland, H.A Crockard
Journal: Annals of the Rheumatic Diseases (1996)

To be able to measure disability objectively in rheumatoid arthritis complicated by cervical myelopathy. The responses to the Stanford health assessment questionnaire disability index were recorded from 250 consecutive patients (group 1) referred to our unit for spinal surgery. Using principal components analysis the questionnaire was reduced from 20 questions to 10 questions. In the second part of the study, the results of the questionnaire for those patients undergoing surgery from the original group of 250 patients were analysed with respect to outcome. The reduction in the number of questions results in no significant loss of information, reliability (internal consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the myelopathy disability index, measures only one dimension (Eigen value 6.97) and may be more finely tuned to the measurement of disability in these myelopathic patients. When administered to the 194 patients undergoing cervical spine (group 2) surgery the myelopathy disability index was an accurate predictor of neurological and functional outcome, as well as survival following surgery (P < 0.0001). The myelopathy disability index provides a much needed objective and reliable means of assessing disability in patients with rheumatoid involvement of the cervical spine and also in predicting outcome following surgical intervention. It also provides information for both the patient and surgeon alike, on what to realistically expect from surgery. Its adoption should facilitate comparisons between different forms of surgical intervention.
A Six-Nucleotide Insertion-Deletion Polymorphism in the <i>CASP8</i> Promoter Associated with Risk and Progression of Bladder Cancer
Authors: Meilin Wang, Zhizhong Zhang, Yuanyuan Tian, Jianfeng Shao, Zhengdong Zhang
Journal: Clinical Cancer Research (2009)

Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer.In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking.A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed.These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.
Phase I Dose-Escalation Trial of the Oral Investigational Hedgehog Signaling Pathway Inhibitor TAK-441 in Patients with Advanced Solid Tumors
Authors: Jonathan Goldman, S. Gail Eckhardt, Mitesh J. Borad, Kelly K. Curtis, Manuel Hidalgo, Emiliano Calvo, David P. Ryan, Lori J. Wirth, Asit Parikh, James Partyka, Helene Faessel, Esha Gangolli, Sally Stewart, Lee S. Rosen, Daniel W. Bowles
Journal: Clinical Cancer Research (2014)

This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway.Patients with advanced, solid tumors received daily oral TAK-441 (50-1,600 mg/day); daily dose was doubled in each subsequent cohort until the maximum tolerated/feasible dose (MTD/MFD) was reached. Blood was collected to evaluate TAK-441 plasma concentrations. Skin biopsies were obtained to evaluate suppression of the Hedgehog-regulated gene Gli1.Thirty-four patients were enrolled (median age 59). The most common diagnoses were colorectal cancer (26%), basal cell carcinoma (BCC, 21%), and pancreatic cancer (9%). The MFD of 1,600 mg/day (based on tablet size and strength) was considered the MTD. Dose-limiting toxicities included muscle spasms and fatigue. Grade ≥3 treatment-emergent adverse events, regardless of causality, occurred in 15 patients (44%), of which hyponatremia (n = 4) and fatigue (n = 3) were most common. Oral absorption was fairly rapid; median Tmax was 2.0 to 4.0 hours after a single dose. Mean elimination half-life was 13.5 to 22.6 hours. Systemic exposure of TAK-441 based on the area under the plasma concentration-time curve was linear across the dose range. Gli1 expression in skin biopsies was strongly inhibited at all dose levels. Best response was partial response (1 patient with BCC) and stable disease (7 patients with various solid tumors).TAK-441 was generally well tolerated up to MFD of 1,600 mg/day, with preliminary antitumor activity. Further study of TAK-441 may be appropriate in populations selected for tumors with ligand-dependent or independent Hedgehog signaling.
Piecing the puzzle together: foreign-born tuberculosis in an immigrant-receiving country
Authors: D Langlois-Klassen, K M Wooldrage, J Manfreda, K Sutherland, E Ellis, M Phypers, B Gushulak, R Long
Journal: European Respiratory Journal (2011)

In major immigrant-receiving countries, annual foreign-born tuberculosis (TB) case counts and rates are relatively constant. Why this is so, and who might be a high-yield target for screening for latent TB infection, remain open questions. Foreign-born TB in Canada during 1986–2002 was retrospectively examined using national TB and immigration data as well as census data. Case counts and rates were analysed in relation to demographics, immigration period and time since arrival. Pre-1986 immigrants (n=3,860,853) and 1986–2002 immigrants (n=3,463,283) contributed 8,662 and 9,613 TB cases, respectively. Immigrants arriving ≤5 yrs ago and those arriving &gt;10 yrs ago contributed almost equally to the annual foreign-born TB case count despite a 3.5-fold difference in in-country person-yrs. Remarkably stable and relatively low TB incidence was observed among immigrants &gt;10 yrs post-arrival. Conversely, TB incidence within 5 yrs of arrival was dynamic, demonstrating a strong inverse association with time since arrival and higher sensitivity to changes in immigration level than shifts toward higher incidence source countries. Relative constancy in foreign-born TB incidence is explained by a complex convergence of several factors. Immigrants born in high-incidence countries who arrived ≤2 yrs ago and were aged 15–34 yrs upon arrival constitute high-yield targets for preventive therapy.
<b> <i>HPC1/RNASEL</i> </b> Mediates Apoptosis of Prostate Cancer Cells Treated with 2′,5′-Oligoadenylates, Topoisomerase I Inhibitors, and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
Authors: Krishnamurthy Malathi, Jayashree M. Paranjape, Ram Ganapathi, Robert H. Silverman
Journal: Cancer Research (2004)

The hereditary prostate cancer 1 (HPC1) allele maps to the RNASEL gene encoding a protein (RNase L) implicated in the antiviral activity of interferons. To investigate the possible role of RNase L in apoptosis of prostate cancer cells, we decreased levels of RNase L by severalfold in the DU145 human prostate cancer cell line through the stable expression of a small interfering RNA (siRNA). Control cells expressed siRNA with three mismatched nucleotides to the RNase L sequence. Cells deficient in RNase L, but not the control cells, were highly resistant to apoptosis by the RNase L activator, 2',5'-oligoadenylate (2-5A). Surprisingly, the RNase L-deficient cells were also highly resistant to apoptosis by combination treatments with a topoisomerase (Topo) I inhibitor (camptothecin, topotecan, or SN-38) and tumor necrosis factor-related apoptosis-inducing ligand [TRAIL (Apo2L)]. In contrast, cells expressing siRNA to the RNase L inhibitor RLI (HP68) showed enhanced apoptosis in response to Topo I inhibitor alone or in combination with TRAIL. An inhibitor of c-Jun NH(2)-terminal kinases reduced apoptosis induced by treatment with either 2-5A or the combination of camptothecin and TRAIL, thus implicating c-Jun NH(2)-terminal kinase in the apoptotic signaling pathway. Furthermore, prostate cancer cells were sensitive to apoptosis from the combination of 2-5A with either TRAIL or Topo I inhibitor, whereas normal prostate epithelial cells were partially resistant to apoptosis. These findings indicate that RNase L integrates and amplifies apoptotic signals generated during treatment of prostate cancer cells with 2-5A, Topo I inhibitors, and TRAIL.
Dissolution of Thrombotic Arterial Occlusion by High Intensity, Low Frequency Ultrasound and Dodecafluoropentane Emulsion: An In Vitro and In Vivo Study
Authors: Toshihiko Nishioka, Huai Luo, Michael C Fishbein, Bojan Cercek, James S Forrester, Chong-Jin Kim, Hans Berglund, Robert J Siegel
Journal: Journal of the American College of Cardiology (1997)
Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Authors: Bruce D. Cheson, Richard I. Fisher, Sally F. Barrington, Franco Cavalli, Lawrence H. Schwartz, Emanuele Zucca, T. Andrew Lister
Journal: Journal of Clinical Oncology (2014)

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.
Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy
Authors: Huib A.M. Kerstjens, Michael Engel, Ronald Dahl, Pierluigi Paggiaro, Ekkehard Beck, Mark Vandewalker, Ralf Sigmund, Wolfgang Seibold, Petra Moroni-Zentgraf, Eric D. Bateman
Journal: New England Journal of Medicine (2012)

Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs).
Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study
Authors: N Ganne-Carrie
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. <h3>METHODS</h3> Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. <h3>RESULTS</h3> 130 patients had detectable iron at enrolment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). <h3>CONCLUSIONS</h3> These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.