tbuckley/cabot-search huggingface dataset:
Incorporation of primary patient-derived glycoproteins into authentic infectious hepatitis C virus particles
Authors: Juliane Doerrbecker, Martina Friesland, Nina Riebesehl, Corinne Ginkel, Patrick Behrendt, Richard J.P. Brown, Sandra Ciesek, Heiner Wedemeyer, Christoph Sarrazin, Lars Kaderali, Thomas Pietschmann, Eike Steinmann
Journal: Hepatology (2014)

The Japanese fulminant hepatitis-1 (JFH1)-based hepatitis C virus (HCV) infection system has permitted analysis of the complete viral replication cycle in vitro . However, lack of robust infection systems for primary, patient-derived isolates limits systematic functional studies of viral intrahost variation and vaccine development. Therefore, we aimed at developing cell culture models for incorporation of primary patient-derived glycoproteins into infectious HCV particles for in-depth mechanistic studies of envelope gene function. To this end, we first constructed a packaging cell line expressing core, p7, and NS2 based on the highly infectious Jc1 genotype (GT) 2a chimeric genome. We show that this packaging cell line can be transfected with HCV replicons encoding cognate Jc1-derived glycoprotein genes for production of single-round infectious particles by way of trans -complementation. Testing replicons expressing representative envelope protein genes from all major HCV genotypes, we observed that virus production occurred in a genotype- and isolate-dependent fashion. Importantly, primary GT 2 patient-derived glycoproteins were efficiently incorporated into infectious particles. Moreover, replacement of J6 (GT 2a) core, p7, and NS2 with GT 1a-derived H77 proteins allowed production of infectious HCV particles with GT 1 patient-derived glycoproteins. Notably, adaptive mutations known to enhance virus production from GT 1a-2a chimeric genomes further increased virus release. Finally, virus particles with primary patient-derived E1-E2 proteins possessed biophysical properties comparable to Jc1 HCVcc particles, used CD81 for cell entry, were associated with ApoE and could be neutralized by immune sera. Conclusion : This work describes cell culture systems for production of infectious HCV particles with primary envelope protein genes from GT 1 and GT 2-infected patients, thus opening up new opportunities to dissect envelope gene function in an individualized fashion. (Hepatology 2014;60:508–520)
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma
Authors: Christian Steidl, Arjan Diepstra, Tang Lee, Fong Chun Chan, Pedro Farinha, King Tan, Adele Telenius, Lorena Barclay, Sohrab P. Shah, Joseph M. Connors, Anke van den Berg, Randy D. Gascoyne
Journal: Blood (2012)
Novel Staging System for Predicting Disease-Specific Survival in Patients With Breast Cancer Treated With Surgery As the First Intervention: Time to Modify the Current American Joint Committee on Cancer Staging System
Authors: Min Yi, Elizabeth A. Mittendorf, Janice N. Cormier, Thomas A. Buchholz, Karl Bilimoria, Aysegul A. Sahin, Gabriel N. Hortobagyi, Ana Maria Gonzalez-Angulo, Sheng Luo, Aman U. Buzdar, Jaime R. Crow, Henry M. Kuerer, Kelly K. Hunt
Journal: Journal of Clinical Oncology (2011)

Purpose American Joint Committee on Cancer (AJCC) staging is used to determine breast cancer prognosis, yet patient survival within each stage shows wide variation. We hypothesized that differences in biology influence this variation and that addition of biologic markers to AJCC staging improves determination of prognosis. Patients and Methods We identified a cohort of 3,728 patients who underwent surgery as the first intervention between 1997 and 2006. A Cox proportional hazards model, with backward stepwise exclusion of factors and stratification on pathologic stage (PS), was used to test the significance of adding grade (G), lymphovascular invasion (L), estrogen receptor (ER) status (E), progesterone receptor (PR) status, combined ER and PR status (EP), or combined ER, PR, and human epidermal growth factor receptor 2 status (M). We assigned values of 0 to 2 to these disease-specific survival (DSS) –associated factors and assessed six different staging systems: PS, PS + G, PS + G L, PS + G E, PS + G EP, and PS + G M. We compared 5-year DSS rates, Akaike's information criterion (AIC), and Harrell's concordance index (C-index) between systems. Surveillance, Epidemiology, and End Results data were used as the external validation cohort (n = 26,711). Results Median follow-up was 6.5 years, and 5-year DSS rate was 97.4%. The PS + G E status staging system was most precise, with a low AIC (1,931.9) and the highest C-index (0.80). PS + G E status was confirmed to stratify outcomes in internal bootstrapping samples and the external validation cohort. Conclusion Our results validate an improved breast cancer staging system that incorporates grade and ER status. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system.
Colorectal Cancers with Microsatellite Instability Display Unique miRNA Profiles
Authors: Francesc Balaguer, Leticia Moreira, Juan Jose Lozano, Alexander Link, Georgina Ramirez, Yan Shen, Miriam Cuatrecasas, Mildred Arnold, Stephen J. Meltzer, Sapna Syngal, Elena Stoffel, Rodrigo Jover, Xavier Llor, Antoni Castells, C. Richard Boland, Meritxell Gironella, Ajay Goel
Journal: Clinical Cancer Research (2011)

microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite instability (MSI).We analyzed genome-wide miRNA expression profiles in 54 CRC tissues [22 with Lynch syndrome, 13 with sporadic MSI due to MLH1 methylation, 19 without MSI (or microsatellite stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI-positive samples (13 with Lynch syndrome and 20 with sporadic MSI), we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR.We found that the expression of a subset of nine miRNAs significantly discriminated between tumor and normal colonic mucosa tissues (overall error rate = 0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor capable of differentiating between types of MSI in an independent sample set.CRC tissues show distinct miRNA expression profiles compared with normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadic MSI, and sporadic MSS colorectal cancers provides novel insights into the role of miRNAs in colorectal carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment of this disease.
Rat mesangial cells express macrophage migration inhibitory factor in vitro and in vivo.
Authors: G H Tesch, D J Nikolic-Paterson, C N Metz, W Mu, M Bacher, R Bucala, R C Atkins, H Y Lan
Journal: Journal of the American Society of Nephrology (1998)

Mesangial cells are thought to promote glomerular macrophage accumulation in glomerulonephritis. This may occur through the production of macrophage migration inhibitory factor (MIF), a molecule known to regulate macrophage accumulation at sites of inflammation. To study this, glomerular MIF expression and macrophage accumulation were examined in rat anti-Thy-1 disease, a model of mesangioproliferative nephritis. In situ hybridization and immunohistochemistry showed that MIF is expressed by some podocytes in normal rat glomeruli. De novo MIF expression by glomerular endothelium was seen on day 1 of anti-Thy-1 disease. On day 6, glomerular MIF mRNA and protein expression were prominent in segmental proliferative lesions, which was also the location of most infiltrating macrophages. Double-staining identified de novo MIF mRNA and protein expression by proliferating mesangial cells within these lesions. Cytokine regulation of mesangial cell MIF expression was examined in vitro. Northern blotting showed that cultured rat mesangial cells express a single 0.6-kb species of MIF mRNA, and Western blotting detected a single protein band of 12.5 kD. Six-hour stimulation of mesangial cells with interferon-gamma or platelet-derived growth factor significantly increased MIF mRNA levels. However, the addition of recombinant MIF to mesangial cells did not affect mesangial cell proliferation or constitutive transforming growth factor-beta mRNA expression, nor did MIF induce monocyte chemoattractant protein-1 mRNA expression. In conclusion, this is the first study to demonstrate that mesangial cells can produce MIF in vivo and in vitro. It is postulated that mesangial cell MIF production in response to injury acts to promote macrophage accumulation within segmental proliferative lesions in rat anti-Thy-1 nephritis.
Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas
Authors: Min Sun Shin, Hong Sug Kim, Chang Suk Kang, Won Sang Park, Su Young Kim, Shi Nae Lee, Jong Heun Lee, Jik Young Park, Ja June Jang, Chul Woo Kim, Sang Ho Kim, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee
Journal: Blood (2002)
Hypnoanalgesia for Chronic Pain: The Response to Multiple Inductions at One Session and to Separate Single Inductions
Authors: D O Lewis
Journal: Journal of the Royal Society of Medicine (1992)

Serial hypnotic inductions conveying the same analgesic message produce a progressively longer response in an increasing number of patients. The resulting analgesia appears to be independent of the spacing of inductions--whether given at a single session or on separate occasions--and to depend upon their number. However, multiple inductions at a single session save time. Elimination of pain can be achieved, by either approach, for a year or more in up to 70% of patients.
Interactions among inflammatory mediators on edema formation in the canine forelimb.
Authors: E Amelang, C M Prasad, R M Raymond, G J Grega
Journal: Circulation Research (1981)

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.
Equipment needs for noninvasive mechanical ventilation
Authors: B. Schönhofer, S. Sortor-Leger
Journal: European Respiratory Journal (2002)

Noninvasive mechanical ventilation (NIV) has a long tradition for the treatment of chronic respiratory failure and more recently has also been applied in acute respiratory failure. Based on this experience both critical care ventilators and portable ventilators are used to perform NIV. The individual choice of ventilator type should depend on the patient's condition and also on the expertise of attending staff, therapeutic requirements and the location of care. The majority of studies have used pressure-targeted ventilation in the assist mode. Positive qualities of pressure support ventilation (PSV) are leak compensation, good patient/ventilator synchrony and the option of integrated positive end-expiratory pressure to counteract the effect of dynamic hyperinflation. In this article, some crucial issues concerning PSV ( i.e. triggering into inspiration, pressurisation, cycling into expiration and carbon dioxide rebreathing) and some corrective measures are discussed. The parameters which should be monitored during noninvasive ventilation are presented. The interface between patient and ventilator is a crucial issue of noninvasive ventilation. Advantages and disadvantages of face and nasal masks are discussed. Finally, causes and possible remedies of significant air leaks and some technical accessories for noninvasive ventilation are dealt with.
Leukocytes are required for increased lung microvascular permeability after microembolization in sheep.
Authors: M R Flick, A Perel, N C Staub
Journal: Circulation Research (1981)

We studied the effects of uneven pulmonary artery obstruction by microemboli on steady state transvascular fluid and protein exchange in normal and leukopenic sheep. We measured pulmonary artery and left atrial pressures, cardiac output, lung lymph flow, and lymph plasma protein concentrations. Sheep were made profoundly leukopenic by administration of intra-arterial mechlorethamine hydrochloride (0.4 mg/kg, two doses) and colchicine (0.1-0.2 mg/kg, anesthetized sheep only). In anesthetized sheep, we injected glass beads 200 micrometers in diameter via the right atrium to raise pulmonary vascular resistance to 2-3 times baseline values. With normal levels of circulating leukocytes, sheep developed an increased protein-rich lymph flow from the lung characteristic of increased permeability edema. Leukopenic sheep had a significantly attenuated response after embolization for equivalent degrees of vascular obstruction. In unanesthetized sheep, we continuously infused air bubbles 1 mm in diameter via the right atrium to raise pulmonary vascular resistance to about 2 times baseline values. Each sheep served as its own control. With normal circulating leukocyte levels, there was an increase in protein-rich lymph flow from the lung during embolization. When the air infusion ended, the sheep recovered to the baseline condition in 24 hours. We induced emboli with the same amount of air when the sheep were profoundly leukopenic; lymph and protein flow from the lung were significantly less for equivalent degrees of obstruction. We conclude that circulating leukocytes are essential for the microvascular injury that results in increased permeability in the lungs of sheep after microembolization.
Strategic Approaches to Unraveling Genetic Causes of Cardiovascular Diseases
Authors: A.J. Marian, John Belmont
Journal: Circulation Research (2011)

DNA sequence variants are major components of the "causal field" for virtually all medical phenotypes, whether single gene familial disorders or complex traits without a clear familial aggregation. The causal variants in single gene disorders are necessary and sufficient to impart large effects. In contrast, complex traits are attributable to a much more complicated network of contributory components that in aggregate increase the probability of disease. The conventional approach to identification of the causal variants for single gene disorders is genetic linkage. However, it does not offer sufficient resolution to map the causal genes in small families or sporadic cases. The approach to genetic studies of complex traits entails candidate gene or genome-wide association studies. Genome-wide association studies provide an unbiased survey of the effects of common genetic variants (common disease-common variant hypothesis). Genome-wide association studies have led to identification of a large number of alleles for various cardiovascular diseases. However, common alleles account for a relatively small fraction of the total heritability of the traits. Accordingly, the focus has shifted toward identification of rare variants that might impart larger effect sizes (rare variant-common disease hypothesis). This shift is made feasible by recent advances in massively parallel DNA sequencing platforms, which afford the opportunity to identify virtually all common as well as rare alleles in individuals. In this review, we discuss various strategies that are used to delineate the genetic contribution to medically important cardiovascular phenotypes, emphasizing the utility of the new deep sequencing approaches.
Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells
Authors: Mingzhen Yang, Fang Yuan, Peng Li, Zhongjiao Chen, An Chen, Shuhui Li, Chuanmin Hu
Journal: Molecular Cancer (2012)

Abstract Background Our previous work demonstrated that ectopic expression of interferon regulatory factor 4 binding protein (IBP) was correlated with the malignant behaviour of human breast cancer cells. The mechanisms controlling differential expression of IBP in breast cancer still remain unknown. Results To investigate the mechanism of IBP dysregulation in breast cancer, we identified IBP was a novel p53 target gene. IBP expression was negatively regulated by wild-type p53 and was p53 dependently suppressed by DNA damage agent cisplatin. Furthermore, high levels of IBP were found to decrease cisplatin-induced growth suppression and apoptotic cell death, which was associated with decreased p53 activity and imbalanced Bcl-2 family member expression. Conclusions IBP is a novel p53 target gene which suppresses cisplatin-mediated apoptosis of breast cancer cells via negative feedback regulation of the p53 signalling pathway, suggesting IBP may serve as a target for pharmacologic intervention of breast cancer resistant to cisplatin therapy.
Treatment outcomes of MDR-TB cases registered in Bucharest sector 4 during 2004-2008
Authors: Mirela Tigau, Ileana Dediu, Elmira Ibraim
Journal: European Respiratory Journal (2012)

Introduction: Although the TB incidence rate declined significantly in Romania in the last decade, from 142.2%ooo in 2002 to 90.2%ooo in 2010, the MDR-TB remains at a rate of attention (2.9% in new and 10.9% in retreated cases).Objective: To analyze the treatment outcomes of MDR-TB cases registered in the TB Dispensary of Bucharest Sector 4, in order to optimize the TB control in its territory.Material and methods: We conducted an observational retrospective study of 78 MDR-TB cases registered in Bucharest Sector 4 since December 2004-December 2008. Data have been collected from the TB register of the dispensary, TB information system, treatment records and epidemiological surveys.Results: Out of 78 patients 35 have been included in the DOTS Plus project financed by the Global Fund (GLC group) and 43 have been treated from NTP resources (NTP group).Chronic patients represented 11.5% in GLC group and 30.3% in NTP group. By treatment history, 20% from GLC group and 46.5% from NTP group have been treated with second line antiTB drugs in the past. Overall success rate was 3 times higher in the GLC group (82.8%) than in the other (27.9%).New cases had a success rate of 95% in the GLC and only 66.6% in the NTP group. The relapses had a success rate of 72.7% in the GLC compared to 36.8% in the NTP group. The cases with second line medication in them histories have a success rate of 57.1% in the GLC and just 5% in the NTP group.Conclusion: The favorable outcome of MDR-TB patients in DOTS Plus project demonstrates the real benefit brought by this project and its extension to all MDR-TB patients in the country should be required.
Prevalence of Mammographically Dense Breasts in the United States
Authors: Brian L. Sprague, Ronald E. Gangnon, Veronica Burt, Amy Trentham-Dietz, John M. Hampton, Robert D. Wellman, Karla Kerlikowske, Diana L. Miglioretti
Journal: JNCI Journal of the National Cancer Institute (2014)

National legislation is under consideration that would require women with mammographically dense breasts to be informed of their breast density and encouraged to discuss supplemental breast cancer screening with their health care providers. The number of US women potentially affected by this legislation is unknown. We determined the mammographic breast density distribution by age and body mass index (BMI) using data from 1518 599 mammograms conducted from 2007 through 2010 at mammography facilities in the Breast Cancer Surveillance Consortium (BCSC). We applied these breast density distributions to age- and BMI-specific counts of the US female population derived from the 2010 US Census and the National Health and Nutrition Examination Survey (NHANES) to estimate the number of US women with dense breasts. Overall, 43.3% (95% confidence interval [CI] = 43.1% to 43.4%) of women 40 to 74 years of age had heterogeneously or extremely dense breasts, and this proportion was inversely associated with age and BMI. Based on the age and BMI distribution of US women, we estimated that 27.6 million women (95% CI = 27.5 to 27.7 million) aged 40 to 74 years in the United States have heterogeneously or extremely dense breasts. Women aged 40 to 49 years (N = 12.3 million) accounted for 44.3% of this group. The prevalence of dense breasts among US women of common breast cancer screening ages exceeds 25 million. Policymakers and healthcare providers should consider this large prevalence when debating breast density notification legislation and designing strategies to ensure that women who are notified have opportunities to evaluate breast cancer risk and discuss and pursue supplemental screening options if deemed appropriate.
The first and second phase of insulin secretion in naive Chinese type 2 diabetes mellitus
Authors: Jiunn-Diann Lin, Te-Lin Hsia, Chung-Ze Wu, Ching-Chieh Su, Wen-Ya Ma, An-Tsz Hsieh, Chang-Hsun Hsieh, Kun Wang, Yi-Min Chu, Dee Pei
Journal: Metabolism (2009)