tbuckley/cabot-search huggingface dataset:
Activities of Benzphetamine <italic>N</italic>-Demethylase and Aryl Hydrocarbon Hydroxylase in Cells Isolated From γ-Glutamyl Transpeptidase-Positive Foci and Surrounding Liver<xref ref-type="fn" rid="FN2">2</xref>
Authors: Marie H. Hanigan, Henry C. Pitot
Journal: JNCI Journal of the National Cancer Institute (1985)

The levels of two cytochrome P-450-linked enzymes of xenobiotic metabolism, benzphetamine N- demethylase and aryl hydrocarbon hydroxylase, were determined in cells isolated from γ-glutamyl transpeptidase (GGT)-positive foci and in cells from surrounding liver obtained from carcinogen-treated inbred F344 rats. Rat liver foci were initiated with diethylnitrosamine (CAS: 55-18-5) and promoted with sodium phenobarbital [(PB) CAS: 64038-21-7] for 4½ or 12 months. The levels of both enzymes were relatively low in the GGT-positive hepatocytes, while the GGT-negative hepatocytes from the surrounding liver had elevated levels of both enzymes comparable to levels seen in rats treated with PB alone. After 12 months of promotion the PB was removed from the diet and the activities of both enzymes fell below the control levels in the GGT-positive hepatocytes and returned to the control levels in the surrounding GGT-negative hepatocytes. Therefore, the cells in the GGT-positive foci contained low levels of these two cytochrome P-450 enzymes in relation to the levels in GGT-negative cells. These levels were responsive to phenobarbital induction, although the induced levels in the GGT-positive cells were much lower than the induced levels in GGT-negative hepatocytes. The liver surrounding the foci responded to phenobarbital induction to the same degree as did the liver of noninitiated rats.
In autoimmune hepatitis type 1 or the autoimmune hepatitis–sclerosing cholangitis variant defective regulatory T‐cell responsiveness to IL‐2 results in low IL‐10 production and impaired suppression
Authors: Rodrigo Liberal, Charlotte R. Grant, Beth S. Holder, John Cardone, Marc Martinez‐Llordella, Yun Ma, Michael A. Heneghan, Giorgina Mieli‐Vergani, Diego Vergani, Maria Serena Longhi
Journal: Hepatology (2015)

Defective immune regulation plays a permissive role enabling effector cells to initiate and perpetuate tissue damage, eventually resulting in autoimmune disease. Numerical and functional regulatory T‐cell (Treg) impairment has been previously reported in autoimmune liver disease (AILD; including autoimmune hepatitis and autoimmune sclerosing cholangitis ASC). However, in these early reports, Tregs were phenotypically defined as CD4 + CD25 + or CD4 + CD25 high cells. In the current study, we reexamined phenotypic and functional properties of Tregs by adopting a more refined definition of these cells that also includes negativity or low level of expression of CD127. We studied 43 AILD patients and 22 healthy subjects (HSs) and found that CD4 + CD25 + CD127 − Tregs were decreased in the former. This decrease was more marked in patients with active disease than in those in remission. In AILD, Treg frequencies correlated inversely with parameters of disease activity and were not affected by immunosuppressive treatment. We also document, for the first time, that, in AILD, bona‐fide Tregs produce less interleukin (IL)−10 and are impaired in their ability to suppress CD4 + CD25 − target cell proliferation, a feature that in HSs, but not in AILDs, is dependent, at least in part, on IL‐10 secretion. Decreased IL‐10 production by Tregs in AILD is linked to poor responsiveness to IL‐2 and phospho signal transducer and activator of transcription 5 up‐regulation. Conclusion : Tregs are numerically impaired in AILD, this impairment being more prominent during active disease. Notably, defective IL‐10 production, resulting from low Treg responsiveness to IL‐2, contributes to Treg functional impairment. (H epatology 2015;62:863–875)
My Winding Road: From Microbiology to Toxicology and Environmental Health
Authors: Linda S. Birnbaum
Journal: The Annual Review of Pharmacology and Toxicology (2015)

I would certainly never have predicted that I would become the director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP) when I was a Jewish girl growing up in Teaneck, New Jersey. My family stressed the importance of education. Yet for a girl there were many not-so-subtle suggestions that the appropriate careers were in teaching or nursing, and the most important thing was to be a wife and mother. Well, I can't disagree with the latter, although I would have to add grandmother to that list of achievements. My parents were both college graduates, but my mom only taught high school English for one year before leaving the field to start our family. My dad returned from World War II and joined his brother in accounting. After my first sister was born, my father joined my mother's family jewelry business and helped to open a second retail store. My mother helped my dad out during the busy times—Christmas and wedding season—but otherwise focused on our growing family of three girls and one boy. This became increasingly challenging when it became clear that my little brother was severely retarded and would require extra care.
Prevalence of asthma and allergy symptoms and pulmonary function testing in sugar cane and tobacco field workers in Honduras
Authors: John Stevens, Howard Eigen, Mario Diaz
Journal: European Respiratory Journal (2011)

We previously demonstrated a very high prevalence of wheezing (89%) and lower pulmonary function tests (PFT) in rural Honduran children of the Rio Grande O Choluteca valley where sugar cane is burned 8 months of the year compared to children of Jamastran valley (17% wheezing) where no crops are burned. We applied a similar asthma/allergy questionnaire and performed PFT on sugar cane field workers (SC) of the Rio Grande O Choluteca valley and tobacco field workers (TOB) of the Jamastran valley. Tables 1 & 2 summarize questionnaire findings and PFT values of the two groups.  We found the SC workers to be significantly younger with thus fewer years working in the fields compared to the TOB workers. Both groups were found to have similarly high prevalence9s of ever wheezed, wheezed in last 12 months, night cough, smoking frequency, chronic rhinitis and conjunctivitis. SC workers have significantly lower FVC and FEV-1. We conclude that both SC and TOB field workers in Honduras have a high prevalence of asthma and allergy symptoms and SC workers, although younger with fewer years of exposure, have lower pulmonary function. Individual air quality sampling of the two groups is needed to delineate the contribution of environmental work exposure to these findings.
Examiner alignment and assessment in clinical periodontal research
Authors: Arthur F. Hefti, Philip M. Preshaw
Journal: Periodontology 2000 (2012)

Abstract Periodontal research typically relies on clinical examiners to assess variables such as gingival inflammation, plaque scores or probing depths as a means of determining treatment outcomes or for performing group comparisons. The quality of the gathered information is dependent, to a large extent, on the skills of the examiner(s) and on the validity of the assessment methods that are used. Attempts have been made to increase the objectivity of periodontal assessments, for example by introducing scoring systems for gingival inflammation, but within these systems there is often considerable scope for variation when interpreting the scoring criteria, leading to subjectivity when assigning scores to individual periodontal sites. This has led to an awareness of the importance of examiner alignment and assessment to improve the data quality by standardizing techniques and improving examiner reliability. Examiner alignment and assessment is used in preference to the term ‘examiner calibration’ because calibration implies comparison with an accurate or ‘gold’ standard, which is not available in periodontal research. In this review, we consider the historical perspective that led to the development of clinical scoring systems for periodontal research using gingival inflammation as an example. A clinical protocol for undertaking examiner alignment and assessment is presented, and we review the common sources of error and bias that can lead to difficulties in aligning examiners, and consider how they can be eliminated. It is particularly important that subjects who are recruited to the examiner alignment and assessment study present with a comparable level of disease to the subjects who will ultimately be recruited to the planned clinical trial. Another challenge in examiner alignment and assessment is applying appropriate statistical tests to assess the outcome of the alignment exercise. In the periodontal literature, the statistic kappa is frequently used to confirm an adequate degree of examiner agreement, but kappa is bound to significant restrictions when applied for this purpose. Through the use of case studies, we present different approaches to data analysis from calibration studies, focusing on continuous variables (such as probing depths and attachment levels) or ordinal data (such as gingival or plaque indices), to enable a correct, although frequently conservative, interpretation of data generated during examiner alignment and assessment studies.
Improved detection of mycobacterium tuberculosis using an inhibitor-tolerant loop-mediated isothermal amplification
Authors: Ehsan Aryan, Zahra Meshkat, Seyedeh-Zohreh Mirbagheri, Amir-Hooshang Alvandi, Hadi Safdari, Bamdad Riahi, Mastoureh Momen-Heravi
Journal: European Respiratory Journal (2014)

Conventional methods remain as the cornerstone of laboratory diagnosis of tuberculosis (TB). However, certain drawbacks of these approaches have attracted attentions to the development of newer molecular methods for detection of Mycobacterium tuberculosis (Mtb). To reliably detect Mtb in clinical specimens, we developed a loop-mediated isothermal amplification (LAMP) reaction targeting mpt64, a gene presents in all strains of Mtb, and the results were compared with mpt64-nested PCR (nPCR). Eighty five out of 189 clinical specimens evaluated in this cross-section study were rule out to have TB and they were used to calculate the specificity of the reactions that was 89.4% (76/85, 95% confidence interval [CI], 81-95%) and 84.7% (72/85, CI, 75.3-92%) respectively for nPCR and LAMP. Although the analytical sensitivity of nPCR was 1000-fold greater than the one obtained by the LAMP, the overall diagnostic sensitivity of LAMP (84.6% [88/104], CI, 76.2-91%) was higher than the one of nPCR (71.2% [74/104], CI, 62-80%). Interestingly, further analysis showed that 90% (27/30) of false-negative nPCR results were due to the presence of inhibitors in clinical specimens, while 77.8% (21/27) of these specimens were positive by the LAMP.  Accordingly, significant higher tolerance of LAMP to inhibitors than that of nPCR ( p 0.0001) leads to improved detection of Mtb using this new generation of gene amplification method. Moreover, lack of popular genes such as IS6110 in some strains of Mtb poses mpt64 as a more reliable target.
Clinical features and CT findings of anti-Jo-1 antibody positive interstitial lung disease with or without polymyositis and dermatomyositis
Authors: Maki Tanaka, Machiko Arita, Hiromasa Tachibana, Tadashi Ishida, Takashi Nakazawa
Journal: European Respiratory Journal (2013)

Background: Anti-Jo-1 antibodies are specific for polymyositis and dermatomyositis (PM/DM). The correlation between the presence of the anti-Jo-1 antibodies and interstitial lung disease (ILD) is very high. Clinical differences for patients with anti-Jo-1 antibody positive ILD without a PM/DM diagnosis are yet to be established.

Aim: To clarify the differences in clinical characteristics, the clinical course, and radiological findings between anti-Jo-1 antibody positive ILD patients with and without a PM/DM diagnosis.

Methods: Twenty-three patients were diagnosed with anti-Jo-1 antibody positive ILD at our hospital between May 1995 and March 2012, inclusive. We evaluated the symptoms, clinical presentation (acute or gradual onset) and dominant chest computed tomography (CT) findings.

Results: Eleven patients were diagnosed with PM/DM. Eight patients (72%) from the PM/DM group and four patients (33%) from the non-PM/DM group presented with ILD of acute or sub-acute onset ( p =0.099). Predominant high-resolution CT scan patterns were diffuse ground-glass opacity, reticular shadow, and consolidation with traction bronchiectasis. Distribution was basal-predominant peripheral and along the bronchovascular bundle.

Conclusion: Although there were more patients in the PM/DM group with an acute and sub-acute clinical course, there was no significant difference between the PM/DM and non-PM/DM groups for clinical characteristics, CT findings and prognosis, respectively. Our study suggests that anti-Jo-1 positive ILD patients without PM/DM groups can be treated based on the clinical course of anti-Jo-1 positive ILD with PM/DM.
Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion
Authors: Talitha van der Meulen, Cynthia J Donaldson, Elena Cáceres, Anna E Hunter, Christopher Cowing-Zitron, Lynley D Pound, Michael W Adams, Andreas Zembrzycki, Kevin L Grove, Mark O Huising
Journal: Nature Medicine (2015)
Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study
Authors: Marta Lado, Naomi F Walker, Peter Baker, Shamil Haroon, Colin S Brown, Daniel Youkee, Neil Studd, Quaanan Kessete, Rishma Maini, Tom Boyles, Eva Hanciles, Alie Wurie, Thaim B Kamara, Oliver Johnson, Andrew J M Leather
Journal: The Lancet Infectious Diseases (2015)
Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer.
Authors: B Chevallier, P Fumoleau, P Kerbrat, V Dieras, H Roche, I Krakowski, N Azli, M Bayssas, M A Lentz, M Van Glabbeke
Journal: Journal of Clinical Oncology (1995)

PURPOSE This trial investigated the toxicity and efficacy of docetaxel as first-line chemotherapy in women with heavily pretreated advanced breast cancer. PATIENTS AND METHODS From April 1992 to August 1992, 35 patients with advanced breast cancer from 29 to 65 years of age with a performance status of 0 to 2 were entered onto the study. Docetaxel 100 mg/m2 was administered every 3 weeks as a 1-hour infusion on day 1 without routine premedication for hypersensitivity reactions. Thirty-one patients were assessable for response. Previous adjuvant chemotherapy had been given to 11 patients. RESULTS Five complete responses (CRs) and 16 partial responses (PRs) were observed, for an overall response rate of 67.7% (95% confidence interval, 49% to 83%). A CR occurred at 13 of 45 assessable sites (four liver, two lung, three breast, three lymph node, and one skin). The median duration of response was 44+ weeks, the median time to disease progression 37+ weeks, and the median overall survival time 16+ months. Among 34 patients assessable for toxicity (177 cycles; median, five cycles per patient), the following side effects were reported: nadir neutropenia grade 3 (three patients); grade 4 (31 patients); no grade 3 to 4 infection, acute hypersensitivity-like reaction (10 patients); grade 2 to 3 alopecia (all patients); and grade 2 to 3 nausea and vomiting (six patients). Fluid retention occurred in 26 patients and consisted of weight gain, edema alone (15 patients), or edema associated with serous effusion (11 patients). This side effect led to treatment discontinuation in 16 of 21 responding patients after a median of five cycles and a median cumulative dose of docetaxel of 574 mg/m2. CONCLUSION Our data suggest that docetaxel has major antitumor activity when used as a single cytotoxic agent as first-line chemotherapy in advanced breast cancer.
Tuberculosis: A Comprehensive Clinical Reference
Authors: G.B. Migliori, J. Huggett
Journal: European Respiratory Journal (2009)

Edited by H.S. Schaaf and A.I. Zumla    Published by WB Saunders Elsevier, UK    Pages: 1,046. Price: £99. ISBN: 978‐1‐4160‐3988‐4

Tuberculosis (TB) remains the world's foremost killer among infectious diseases. A vast amount of knowledge has been generated in the field of TB over the past decade, but the growing issue of TB in children and in those infected with HIV remains neglected. This information is not readily available in one volume for practising health workers, especially in developing countries. Thus, there is worldwide need for an up‐todate, comprehensive clinical textbook on developments in TB research, diagnostics, treatment and control.

This comprehensive book, edited by …
Government objects to publishing how many claimants have died after being found fit for work
Authors: G. Iacobucci
Journal: BMJ (2015)

The government has launched an appeal to overturn a ruling from the Information Commissioner’s Office that it should publish figures showing how many people claiming incapacity benefit payments have died after being found fit for work.

The commissioner’s ruling1 found no “convincing evidence” for a delay in the Department for Work and Pensions (DWP) publishing the figures, which were requested under the Freedom of Information Act in 2014 by Mike Sivier, a political campaigner.

The DWP last published such figures in 2012, which showed that 10 600 people who were taken off incapacity benefit and its successor, employment and support allowance, died from January to November 2011. That represented about 1% of those who were receiving the allowance in November 2011. …
Manager at baby food company is under investigation for manslaughter
Authors: O. Dyer
Journal: BMJ (2003)

German state prosecutors have launched an investigation into a manager at the baby food manufacturer Humana after the deaths of two infants in Israel ( BMJ 15 November, News extra).

Harald Krahmuller, spokesman for the state prosecution office in Bielefeld, North Rhine-Westphalia, said that the head of Humana's product development department was expected to be charged with manslaughter and causing grievous bodily …
Neoadjuvant MVAC: The Long and Winding Road Is Getting Shorter and Straighter
Authors: Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.20.4003 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11600600 Neoadjuvant MVAC: The Long and Winding Road Is Getting Shorter and Straighter Nicholas J. VogelzangxNicholas J. VogelzangSearch for articles by this author Show More University of Chicago Cancer Research Center, Chicago, IL https://doi.org/10.1200/JCO.2001.19.20.4003 Full Text PDF Figures and Tables "Neoadjuvant MVAC: The Long and Winding Road Is Getting Shorter and Straighter." Journal of Clinical Oncology, 19(20), pp. 4003–4004© 2001 by American Society of Clinical Oncology
Foreign-Body Tumorigenesis Induced by Glass and Smooth and Rough Plastic Comparative Study of Preneoplastic Events&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: K G Brand, L C Buoen, I Brand
Journal: JNCI Journal of the National Cancer Institute (1975)

Foreign-body (FB) tumorigenesis was induced in female CBH/H and CBA/H-T6 mice and their hybrids by sc implantation of about 0.2-mm thick, large (660-720 mm2) or small (210-400 mm2) pieces of glass, smooth-surfaced plastic, or roughened plastic (rigid unplasticized vinyl chloride vinyl acetate copolymer). The tumorigenic process was analyzed in the various implantation groups by the evaluation of tumor incidences and latencies, and by the determination of 1) frequency of originator ("parent") cells, 2) appearance of preneoplastic cells in FB-reactive capsule tissue, 3) expansion of preneoplastic cell clones throughout the tissue capsule, and 4) pace of cellular preneoplastic maturation in terms of time remaining until neoplastic autonomy. Established methods included transfer of preneoplastic FB-reactive tissue capsules to recipient animals (hybrids of CBA/H and CBA/Br or C57BL/10ScSn). Specific preneoplastic events or stages of FB tumorigenesis were affected differently, depending on the size, material, and surface properties of implants.
Molecular mechanisms of taxane resistance
Authors: Nesrin S. Rechache, Rebecca Riggins, Alan Zwart, Robert Clarke
Journal: Clinical Cancer Research (2006)

B58   Treatment with the taxanes (Paclitaxel or Docetaxel) is often the therapy of choice for women with breast cancer. In most cases, the taxanes can arrest cell proliferation at the G2/M phase and cause cell death. However, some tumors develop resistance during the course of treatment, which is a major concern for both patients and physicians. Several mechanisms of resistance have been proposed to explain how resistance to the taxanes occurs, but this phenomenon remains incompletely understood. Our preliminary gene expression microarray and western blot data in sensitive and resistant MDA-MB-231 cell lines suggest that the expression of apoptotic genes are not significantly altered between sensitive and taxane resistant cells. Western blots specifically for Bcl-2, caspase-7, and Bcl-xL in our sensitive and resistant cell lines showed remarkably little difference, suggesting that alternative non-apoptotic death pathways may be used to support the resistance phenotype. We have also found that cross resistance occurs for Docetaxel resistant cells (these cells are also resistant to Paclitaxel) but full cross resistance does not occur for Paclitaxel resistant cells (retain sensitivity to Docetaxel drug). This suggests that the resistance pathways used by each drug may not be redundant. Finally, our preliminary microarray data show significant differential upregulation of CDC25C (2-fold; p=0.001) in Paclitaxel resistant vs. Docetaxel resistant cells. CDC25C is important in cell cycle progression, particularly through the G2/M phase. In addition, initial exploration of the data from the comparison of genes expressed in Paclitaxel and Docetaxel resistant MDA-MB-231 cells and those that are sensitive to either taxane showed increased expression of both CDK2 and Cyclin B (1.56-fold; p=0.031 and 1.50-fold; p=0.007, respectively), genes also implicated in the cell cycle. From these preliminary data, we propose to further investigate the various alternative cell death pathways seen in breast cancer cells and compare them to levels seen in clinical samples of human breast cancer tissue from responsive and non-responsive patients. We also propose to determine to what extent CDC25C can confer resistance, and whether inhibiting this gene can reverse resistance. Our studies will not only help reveal how cell cycle genes and pathways may contribute to taxane resistance in breast cancer, but will also assist in our understanding of how alternative cell death pathways contribute to the resistance phenotype. Ultimately our studies aim not only to improve our understanding of taxane resistance on the bench but may also provide the framework for formulation of novel therapies that may improve the success of taxane therapy in women with breast cancer in the clinic.
Association of Fibroblast Growth Factor-23 Levels and Angiotensin-Converting Enzyme Inhibition in Chronic Systolic Heart Failure
Authors: Peter Wohlfahrt, Vojtech Melenovsky, Martin Kotrc, Jan Benes, Antonin Jabor, Janka Franekova, Sophia Lemaire, Josef Kautzner, Petr Jarolim
Journal: JACC Heart Failure (2015)