tbuckley/cabot-search huggingface dataset:
Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria
Authors: I. Tillie-Leblond, F. Grenouillet, G. Reboux, S. Roussel, B. Chouraki, C. Lorthois, J-C. Dalphin, B. Wallaert, L. Millon
Journal: European Respiratory Journal (2010)

Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers. 13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established. The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.
Activity of aminopeptidase M, dipeptidylpeptidase IV and g-glutamyltransferase in the gallbladder mucosa of donors for organ transplantation
Authors: O. Marecková, E. Pokorná, M. Ryska, S. Vítko, V. Teplan, J. Spicák, Z. Lojda, J. Šmídová, Z. Marecek, F. Šmíd
Journal: Journal of Hepatology (2001)
Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor.
Authors: J R Weber, G M Bell, M Y Han, T Pawson, J B Imboden
Journal: The Journal of Experimental Medicine (1992)

Stimulation of the T cell antigen receptor (TCR) activates a protein tyrosine kinase and leads to the tyrosine phosphorylation of phosphoinositide-specific phospholipase C-gamma 1 (PLC gamma 1). The molecular interactions involved in this phosphorylation are not known. After stimulation of the TCR on Jurkat T cells, tyrosine-phosphorylated proteins of 36, 38, 58, and 63 kD coprecipitate with PLC gamma 1. An identical pattern of proteins precipitate with TrpE fusion proteins that contain the Src homology (SH) 2 domains of PLC gamma 1, indicating that these regions of PLC gamma 1 are responsible for binding. TCR stimulation leads to an association between the SH2 domains of PLC gamma 1 and a protein tyrosine kinase, which, by peptide mapping, is identical to p56lck. These studies establish that p56lck associates with PLC gamma 1 as a result of TCR stimulation of Jurkat cells, suggesting that p56lck plays a central role in coupling the TCR to the activation of PLC gamma 1.
Placebo-Controlled Trial of Dehydroepiandrosterone (DHEA) for Treatment of Nonmajor Depression in Patients With HIV/AIDS
Authors: Judith G. Rabkin, Martin C. McElhiney, Richard Rabkin, Patrick J. McGrath, Stephen J. Ferrando
Journal: American Journal of Psychiatry (2006)

Subsyndromal major depressive disorder is common among HIV-positive adults. This study was designed to assess the efficacy of dehydroepiandrosterone (DHEA) as a potential treatment.One hundred forty-five patients with subsyndromal depression or dysthymia were randomly assigned to receive either DHEA or placebo; 90% (69 of 77) of the DHEA patients and 94% (64 of 68) of the placebo patients completed the 8-week trial. The primary measure of efficacy was a Clinical Global Impression improvement rating of 1 or 2 (much or very much improved) plus a final Hamilton Depression Rating Scale score <or=8. Outcome was assessed by using intent-to-treat analysis, followed by completer analysis. Safety was assessed by queries about side effects at every study visit plus measures of CD4 cell count and HIV RNA viral load at baseline and week 8. DHEA dosing was flexible (100-400 mg/day).On the basis of clinicians' ratings, DHEA was superior in the intent-to-treat analysis, where the response rate was 56% (43 of 77) for the DHEA group versus 31% (21 of 68) for the placebo group. In the completer analysis, the response rate was 62% (43 of 69) for the DHEA group, compared to 33% (21 of 64) for the placebo patients. The number needed to treat was 4 on the basis of intent-to-treat data and 3.4 on the basis of completer data. Few adverse events were reported in either treatment group, and no significant changes in CD4 cell count or HIV RNA viral load were observed in either group.Nonmajor but persistent depression is common in patients with HIV/AIDS, and DHEA appears to be a useful treatment that is superior to placebo in reducing depressive symptoms. The low attrition rate in this group of physically ill patients, together with requests for extended open-label treatment, reflect high acceptance of this readily available intervention.
Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever
Authors: Judith van Paassen, Martijn P Bauer, M Sesmu Arbous, Leo G Visser, Jonas Schmidt-Chanasit, Stefan Schilling, Stephan Ölschläger, Toni Rieger, Petra Emmerich, Christel Schmetz, Franchette van de Berkmortel, Bart van Hoek, Nathalie D van Burgel, Albert D Osterhaus, Ann CTM Vossen, Stephan Günther, Jaap T van Dissel
Journal: The Lancet Infectious Diseases (2012)
Tal1 Transgenic Expression Reveals Absence of B Lymphocytes
Authors: Alexey Palamarchuk, Nicola Zanesi, Rami I. Aqeilan, Alexey Efanov, Vadim Maximov, Urmila Santanam, John P. Hagan, Carlo M. Croce, Yuri Pekarsky
Journal: Cancer Research (2006)

Abstract TAL1 oncogene encodes a helix-loop-helix transcription factor, Tal1, which is required for blood cell development, and its activation is a frequent event in T-cell acute lymphoblastic leukemia. Tal1 interacts and inhibits other helix-loop-helix factors such as E47 and HEB. To investigate the function of Tal1 in B cells, we generated Eμ-TAL1 transgenic mouse line, expressing Tal1 in mouse B-cell lineage. Fluorescence-activated cell sorting (FACS) analysis of lymphocytes isolated from spleens of five out of five founders reveals complete absence of IgM- or CD19-expressing cells. Only 2% to 3% of these cells were B220+ and 100% of B220+ cells were CD43+, indicating that these mice were able to make pro-B cells. Similarly, FACS analysis of bone marrow cells in Eμ-TAL1 mice revealed complete absence of B220+IgM+ and B220+CD19+ cells. Analysis of the recombination status of IgH genes revealed the presence of D-J but absence or drastic reduction of V-D-J rearrangements. Our results suggest that Tal1 overexpression in B cells results in a phenotype similar to that of B cells of E47/E2A knockout animals. This represents first in vivo evidence that Tal1 can completely inhibit E47/E2A function. (Cancer Res 2006; 66(12): 6014-7)
Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study
Authors: L H M Rijssenbeek-Nouwens
Journal: Thorax (2002)

The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma.Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period.There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC(20) histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group.The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance.
Commentary: Generating Rigorous Evidence for Public Health: The Need for New Thinking to Improve Research and Practice
Authors: Ross C. Brownson, Ana V. Diez Roux, Katherine Swartz
Journal: Annual Review of Public Health (2013)

This commentary describes the concept of evidence-based public health, including the limitations of evidence. Increased attention to evidence may have numerous benefits for public health practice, including access to higher-quality information on what works, a higher likelihood of successful programs and policies being implemented, greater workforce productivity, and more efficient use of resources. To broaden thinking on the sources and scope of evidence, the three reviews in this symposium seek to (a) compare and contrast several evaluation designs that are alternatives to the randomized controlled trial; (b) describe two research approaches that are useful in addressing complex, multilevel public health issues (i.e., mixed methods research and mixed studies reviews); and (c) provide an overview of the value and approaches for generating practice-based evidence. These reviews highlight the complexity and interrelatedness of public health challenges, limitations of researcher-driven, quantitative approaches, and the need to broaden our current concepts of evidence.
Single-Molecule Analysis of the Hypermutable Tetranucleotide Repeat Locus D21S1245 Through Sperm Genotyping: A Heterogeneous Pattern of Mutation but no Clear Male Age Effect
Authors: J. Brohede
Journal: Molecular Biology and Evolution (2003)

Single molecule genotyping of the hypermutable microsatellite locus D21S1245 was used for studying how the rate and pattern of mutation varied between alleles and different age groups. In total, 203 mutation events were scored from the genotyping of DNA corresponding to an estimated 8623 sperm cells from eight different men. Allele-specific mutation rates ranged from 0.007 to 0.052, a heterogeneity related in part to variation in the mutation rate among three allelic lineages identified after allele sequencing. Alleles from these lineages differed in the overall repeat structure of this complex microsatellite locus. Also, the pattern of mutation varied between lineages in that they differed in the relative proportions of expansion and contraction mutations. Surprisingly, a group of four men aged 18–23 years showed a higher mean mutation rate than a group of four men aged 48–56 years. To some extent this age difference can probably be explained by a bias in the distribution of alleles from the three allelic lineages among the age groups. However, the absence of a clear male age effect is at odds with the idea of an increasing male mutation rate with age, which is thought to arise from the continuous replication of germline cells throughout adulthood.
Computer-Aided Breast Cancer Detection Using Mammograms: A Review
Authors: Karthikeyan Ganesan, U. Rajendra Acharya, Chua Kuang Chua, Lim Choo Min, K. Thomas Abraham, Kwan-Hoong Ng
Journal: IEEE Reviews in Biomedical Engineering (2012)

The American Cancer Society (ACS) recommends women aged 40 and above to have a mammogram every year and calls it a gold standard for breast cancer detection. Early detection of breast cancer can improve survival rates to a great extent. Inter-observer and intra-observer errors occur frequently in analysis of medical images, given the high variability between interpretations of different radiologists. Also, the sensitivity of mammographic screening varies with image quality and expertise of the radiologist. So, there is no golden standard for the screening process. To offset this variability and to standardize the diagnostic procedures, efforts are being made to develop automated techniques for diagnosis and grading of breast cancer images. A few papers have documented the general trend of computer-aided diagnosis of breast cancer, making a broad study of the several techniques involved. But, there is no definitive documentation focusing on the mathematical techniques used in breast cancer detection. This review aims at providing an overview about recent advances and developments in the field of Computer-Aided Diagnosis (CAD) of breast cancer using mammograms, specifically focusing on the mathematical aspects of the same, aiming to act as a mathematical primer for intermediates and experts in the field.
Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer
Authors: R. Caspari, W. Friedl, M. Mandl, P. Propping, G. Möslein, M. Kadmon, G. Timmermanns, M. Knapp, K-H. Jacobasch, K-W. Ecker, D. Kreiβler-Haag
Journal: The Lancet (1994)
Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease
Authors: Corey Casper, Shalini Chaturvedi, Nikhil Munshi, Raymond Wong, Ming Qi, Michael Schaffer, Rajesh Bandekar, Brett Hall, Helgi van de Velde, Jessica Vermeulen, Manjula Reddy, Frits van Rhee
Journal: Clinical Cancer Research (2015)

Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD). Effects of IL6 inhibition on the inflammatory milieu accompanying MCD have not been characterized.Trends in inflammatory- and anemia-associated markers, measured over the course of a placebo-controlled study of siltuximab (11 mg/kg q3w) in patients with MCD (n = 79), were characterized.Baseline IL6 and C-reactive protein (CRP) levels were significantly correlated (r = 0.708; P < 0.0001). CRP levels decreased (median, 92%) by cycle 1 day 8 (C1D8), remaining suppressed during siltuximab treatment while remaining stable in the placebo group. There were no associations between baseline CRP or IL6 and MCD symptom burden, histologic subtype, ethnicity, maximum CRP decrease, and response parameters. A hemoglobin response (change ≥ 15 g/L at week 13) was observed with siltuximab (61%; P = 0.0002). Median hepcidin decrease from baseline at C1D8 with siltuximab was 47% versus median 11% increase with placebo. Maximum post-baseline changes in hepcidin levels among siltuximab recipients were correlated with maximum changes for hemoglobin (r = -0.395; P = 0.00607), total iron-binding capacity (TIBC; r = -0.354; P = 0.01694), and ferritin (r = 0.599; P = 0.0001). Greater median changes from baseline in ferritin, hemoglobin, and TIBC were observed in anemic siltuximab-treated patients.IL6 neutralization with siltuximab resulted in sustained CRP suppression and improvement of anemia, in part, by hepcidin pathway inhibition.
Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis
Authors: Alexander Gelbard, Charlie T. Garnett, Scott I. Abrams, Vyomesh Patel, J. Silvio Gutkind, Claudia Palena, Kwong-Yok Tsang, Jeffrey Schlom, James W. Hodge
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis. Experimental Design: Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8+ CTL directed against carcinoembryonic antigen or MUC-1. Results: In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene. Conclusions: Overall, these results reveal that (a) CTL killing can be enhanced by combining multiagent chemotherapy and radiation and (b) combination treatment enhanced or sensitized HNSCC to the perforin pathway, perhaps by down-regulating Bcl-2 expression. These studies thus form the rational basis for clinical trials of immunotherapy concomitant with the current standard of care of HNSCC.
The Total Correction of Congenital Heart Disease in Infants
Authors: E Aberdeen
Journal: Annual Review of Medicine (1975)

If radical correction of congenital heart disease can be performed with a low risk in the first year of life the advantages are obvious. Total correction avoids the latent risks of the underlying lesion and the risks of palliative surgery, and relieves the parents and family of the psychological pressure of a major illness. Palliative surgery, although offering survival, may include the long term problems of the palliative operation itself, and the possibility that cases may be lost to further treatment or follow-up examination after a successful palliative operation. For these reasons, to be desirable, a palliative operation should offer a survival chance that is at least 10% better than the corrective procedure in that patient at that time. That is, any corrective procedure with a mortality rate less than 10% is to be perferred at any age to a palliative operation. An accurate assessment of risk demands a complete diagnostic study, and a knowledge of the natural history of that form of congenital heart disease. The problems of infants with congenital heart disease are not primarily caused by age of size. The main problem is that of natural selection.
A Population-Based, Prospective Study of Blood Pressure and Risk for End-Stage Renal Disease in China
Authors: Kristi Reynolds, Dongfeng Gu, Paul Muntner, John W. Kusek, Jing Chen, Xigui Wu, Xiufang Duan, Chung-Shiuan Chen, Michael J. Klag, Paul K. Whelton, Jiang He
Journal: Journal of the American Society of Nephrology (2007)

The association between BP and risk for ESRD has not been well characterized in Asian populations. This study examined the relationship between level of BP and incidence of ESRD in a prospective cohort study of 158,365 Chinese men and women who were 40 yr and older. Measurement of BP and covariables were made in 1991 following a standard protocol. Follow-up evaluations were conducted in 1999 to 2000 and included interviewing participants or proxies and obtaining medical records and death certificates for ESRD cases. During 1,236,422 person-years of follow-up, 380 participants initiated renal replacement therapy or died from renal failure (30.7 cases per 100,000 person-years). Compared with those with normal BP, the multivariate adjusted hazard ratios (95% confidence interval) of all-cause ESRD for prehypertension and stage 1 and stage 2 hypertension were 1.30 (0.98 to 1.74), 1.47 (1.06 to 2.06), and 2.60 (1.89 to 3.57), respectively (P < 0.001 for trend). The corresponding hazard ratios (95% confidence interval) of glomerulonephritis-related ESRD were 1.32 (0.82 to 2.11), 1.48 (0.83 to 2.61), and 3.40 (2.02 to 5.74), respectively (P <0.001 for trend). Systolic BP was a stronger predictor of ESRD than diastolic BP or pulse pressure. This study provides novel data on the incidence of ESRD and on the association between BP and glomerulonephritis-related ESRD from a nationally representative sample of adults in China. These results document the importance of high BP as a modifiable risk factor for ESRD in China. Strategies to prevent ESRD should incorporate the prevention, treatment, and control of BP.
Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis
Authors: Suruchi Mittal, Deepa Subramanyam, Devaveena Dey, Rekha V Kumar, Annapoorni Rangarajan
Journal: Molecular Cancer (2009)

Abstract Background Recent studies have implicated aberrant Notch signaling in breast cancers. Yet, relatively little is known about the pattern of expression of various components of the Notch pathway, or its mechanism of action. To better understand the role of the Notch pathway in breast cancer, we have undertaken a detailed expression analysis of various Notch receptors, their ligands, and downstream targets at different stages of breast cancer progression. Results We report here that there is a general increase in the expression levels of Notch 1, 2, 4, Jagged1, Jagged2, and Delta-like 4 proteins in breast cancers, with simultaneous upregulation of multiple Notch receptors and ligands in a given cancer tissue. While Notch3 and Delta-like1 were undetectable in normal tissues, moderate to high expression was detected in several cancers. We detected the presence of active, cleaved Notch1, along with downstream targets of the Notch pathway, Hes1/Hes5, in ~75% of breast cancers, clearly indicating that in a large proportion of breast cancers Notch signaling is aberrantly activated. Furthermore, we detected cleaved Notch1 and Hes1/5 in early precursors of breast cancers - hyperplasia and ductal carcinoma in situ - suggesting that aberrant Notch activation may be an early event in breast cancer progression. Mechanistically, while constitutively active Notch1 alone failed to transform immortalized breast cells, it synergized with the Ras/MAPK pathway to mediate transformation. This cooperation is reflected in vivo , as a subset of cleaved Notch positive tumors additionally expressed phopsho-Erk1/2 in the nuclei. Such cases exhibited high node positivity, suggesting that Notch-Ras cooperation may lead to poor prognosis. Conclusions High level expression of Notch receptors and ligands, and its increased activation in several breast cancers and early precursors, places Notch signaling as a key player in breast cancer pathogenesis. Its cooperation with the Ras/MAPK pathway in transformation offers combined inhibition of the two pathways as a new modality for breast cancer treatment.