tbuckley/cabot-search huggingface dataset:
Influence of Race on Kidney Transplant Outcomes within and outside the Department of Veterans Affairs
Authors: Harini A. Chakkera, Ann M. O’Hare, Kirsten L. Johansen, Denise Hynes, Kevin Stroupe, Philip M. Colin, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2004)

Inferior outcomes after kidney transplantation among African Americans are poorly understood. It was hypothesized that unequal access to medical care among transplant recipients might contribute to worse posttransplantation outcomes among African Americans and that racial disparities in kidney transplant outcomes would be less pronounced among patients who receive health care within versus outside the Department of Veterans Affairs (VA), because eligible veterans who receive care within the VA are entitled to receive universal access to care, including coverage of prescription drugs. A study cohort of 79,361 patients who were undergoing their first kidney transplant in the United States between October 1, 1991, and October 31, 2000, was assembled, with follow-up data on graft survival obtained through October 31, 2001. After multivariable proportional hazards adjustment for a wide range of recipient and donor characteristics, African-American patients were at increased risk for graft failure compared with non-African-American patients (relative risk [RR] 1.31; 95% confidence interval [CI] 1.26 to 1.36). African-American race was associated with a similarly increased risk for graft failure among patients who were VA users (RR 1.31; 95% CI 1.11 to 1.54) and non-VA users (RR 1.31; 95% CI 1.26 to 1.36). In conclusion, racial disparities in kidney transplant outcomes seem to persist even in a universal access-to-care system such as the VA. Reasons for worse outcomes among African Americans require further investigation.
High-dose chemotherapy in germ-cell tumors
Authors: J.P. Droz, S. Culine, P. Biron, A. Kramar
Journal: Annals of Oncology (1996)

The majority of patients with advanced-stage germ-cell tumor are curable by cisplatin-based chemotherapy, but about 10% of those in the good-risk and 30%-50% in the poor-risk groups will experience relapse. Patients in first relapse have a 60% chance of entering a second complete remission and a 15%-25% probability that it will be durable. Regimens of high-dose chemotherapy with hematopoietic stem-cell support have been developed specifically for this patient population; they are usually based on combinations of etoposide, cyclophosphamide, ifosfamide and, originally, double-dose cisplatin or, nowadays, high-dose carboplatin. The role of high-dose chemotherapy was studied initially in salvage and later in first-line treatment. Four hundred thirty-six patients who received high-dose salvage chemotherapy have been reported, 96 (22%) of whom have obtained long-term complete remissions. Prognostic factors for outcome were disease status (absolute refractory, refractory or sensitive diseases), primary tumor site, response to prior chemotherapy and serum hCG levels prior to high-dose treatment. Patients with no adverse prognostic factors have a greater than 50% chance of cure after high-dose treatment. Patients with refractory disease did not benefit from high-dose chemotherapy. A randomized European trial is ongoing to evaluate prospectively the role of high-dose chemotherapy in comparison to standard ifosfamide-based salvage treatment. In first-line consolidation treatment of poor-risk non-seminomatous germ-cell tumors, the results of phase II trials with carboplatin-based high-dose therapy are in favor of a survival impact when compared to historical controls. A prospective randomized trial is ongoing in the US to study the role of carboplatin-based high-dose consolidation treatment. The only prospective trial comparing a cisplatin-based high-dose treatment to standard chemotherapy failed to demonstrate any survival advantage for the high-dose procedure in this setting. New developments include the use of repeated cycles of high-dose chemotherapy with peripheral blood stem-cell support and the introduction of paclitaxel, a new active drug in this disease, and other non-cross-resistant cytotoxic agents in high-dose combination regimes.
Paediatric origins of adult lung disease bullet 8: Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy)
Authors: E Eber
Journal: Thorax (2001)

Bronchopulmonary dysplasia (BPD) is the most common form of chronic lung disease in infancy. The clinical, radiological, and pathological features of BPD were first described a little more than three decades ago.1 The disease was then seen in large preterm infants with severe respiratory distress syndrome who had been treated with high inspired oxygen concentrations and prolonged mechanical ventilation with high positive airway pressures resulting in inflammation, fibrosis, and smooth muscle hypertrophy in the airways.2 Despite advances in the prevention and management of respiratory distress syndrome (including the widespread use of antenatal steroids and surfactant treatment), neonatal chronic lung disease is still one of the major complications in mechanically ventilated premature infants. Acceptance of modest hypercapnia with less aggressive application of positive pressure ventilation and reduction of the use of high oxygen concentrations led to a decrease in the incidence of BPD in newborn infants with a birth weight above 1500 g. However, with increased survival of extremely premature infants (24–26 weeks gestation, birth weight  1250 g.3 Apart from differences in patient populations and management, the reported variation in the incidence of BPD might also be due to the use of different criteria to define it.1 11 12 

“Classic” BPD, as described by Northway and colleagues, is a severe form of chronic lung disease that has become less common and has been replaced by less severe forms which are observed in very small premature infants who survive after prolonged mechanical ventilation.8 …
Which Disposable Chest Electrode?
Authors: P. J. B. Hubner
Journal: BMJ (1969)

Chest electrodes are preferred to limb electrodes for cardiac monitoring, as limb movements are not restricted and produce less interference of the E.C.G. trace. Eight types of disposable chest electrodes were investigated to compare their performance, skin reactions, cost, ease of application, size, and skin–electrode impedance. Elema-Schonander electrodes were found to be the most efficient and the most expensive. In their application care was required to avoid severe skin reactions. Dracard electrodes were simple to attach, worked well without severe skin reactions, and were cheap. They are recommended for routine use. Smith and Nephew electrodes, a type of “multipoint electrodes” which do not require electrode jelly, frequently produced severe skin reactions, making them unsuitable for monitoring for periods exceeding 12 hours.
The human mycobiome in health and disease
Authors: Lijia Cui, Alison Morris, Elodie Ghedin
Journal: Genome Medicine (2013)

The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease.
C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation
Authors: Leendert A. Trouw, Sara C. Nilsson, Isabel Gonçalves, Göran Landberg, Anna M. Blom
Journal: The Journal of Experimental Medicine (2005)

After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP–protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP α-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP–necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells.
O7.07 * PET IMAGING OF BRAIN GLIOMAS WITH C-11 ACETATE: COMPARISON WITH F-18 FDG PET
Authors: J. H. Chang, E. Kim, S. Kang, S. Kim, M. Yun
Journal: Neuro-Oncology (2014)

INTRODUCTION: The purpose of this study is to evaluate the clinical value of C-11 acetate(ACE) positron emission tomography(PET), compared with 18F-fluorodeoxyglucose(FDG) PET, in patients with a brain glioma. METHODS: Forty patients with a glioma were prospectively examined by C-11 acetate PET and F-18 FDG PET. Six patients had grade II, 11 had grade III, and 23 had grade IV gliomas. They underwent PET with both FDG and ACE on separate days. Images were analyzed by the tumor-to-cortex ratio(T/C ratio). The tumor uptake was visually scored into 3 grades as compared with that of the contralateral cortex: low(similar to or lower than contralateral cortex), moderate(slightly increased), and intense(markedly increased). RESULT: In grade IV, all lesions showed intense ACE uptake. Seventy four percent(17/23) of grade IV gliomas had intense FDG uptake and 26%(6/23) had moderate FDG uptake. In grade III, all lesions had moderate ACE uptake and there were 27%(3/11) with intense FDG uptake, 64%(7/11) with moderate FDG uptake, and 9%(1/11) with low FDG uptake. In grade II gliomas, all lesions had low ACE and FDG uptake. The mean ACE T/C ratio in grade IV gliomas(2.91 ± 0.89) was significantly higher than that in both grade III gliomas(1.56 ± 0.37; p = 0.001) and grade II gliomas(0.83 ± 0.31; p = 0.002). The mean FDG T/C ratio in grade IV gliomas(1.27 ± 0.42) was significantly higher than that in grade II gliomas(0.57 ± 0.12; p = 0.016), but not in grade III gliomas(1.00 ± 0.59; p = 0.252). FDG PET was not reliable in differentiating grade III gliomas from grade IV gliomas. CONCLUSION: FDG PET and ACE PET seem to be equal in detecting high grade gliomas. However, ACE PET was better in differentiating grade III from IV tumors. Both FDG PET and ACE PET had no positive uptake in grade II gliomas which was well correlated with biological behavior of tumor. ACE seems to be very useful in grading brain gliomas and also have a potential in detecting unsuspected high grade gliomas which is important to decide surgical extent.
Imbalance between subpopulations of regulatory T cells in COPD
Authors: Jia Hou, Yongchang Sun, Yu Hao, Jie Zhuo, Xiaofang Liu, Peng Bai, Junyan Han, Xiwei Zheng, Hui Zeng
Journal: Thorax (2013)

Recent evidence indicates that human regulatory T cells (Tregs) are composed of three distinct subpopulations: CD25(++) CD45RA(+) resting Tregs (rTregs), CD25(+++) CD45RA(-) activated Tregs (aTregs), which are suppressive, and CD25(++) CD45RA(-) cytokine-secreting (Fr III) cells with pro-inflammatory capacity.To evaluate the dynamic changes in circulating and pulmonary Treg subpopulations in smokers and patients with chronic obstructive pulmonary disease (COPD), and to explore their potential roles in COPD pathogenesis.Blood samples were obtained from 57 never-smokers, 32 smokers with normal lung function and 66 patients with COPD. Bronchoalveolar lavage (BAL) samples were taken from 12 never-smokers, 12 smokers and 18 patients with COPD. The proportions of Treg subpopulations and activated CD8 T cells were evaluated using flow cytometry.In peripheral blood, increased proportions of rTregs, aTregs and Fr III cells were found in smokers compared with never-smokers, whereas patients with COPD showed decreased rTregs and aTregs, and significantly increased Fr III cells compared with smokers. The changes in Treg subpopulations, with an overall decrease in the (aTreg+rTreg):(Fr III) ratio, indicated that immune homeostasis favoured inflammation and correlated with enhanced CD8 T-cell activation (r=-0.399, p<0.001) and forced expiratory volume in 1 s (FEV1) % predicted value (r=0.435, p<0.001).The BAL (aTreg+rTreg):(Fr III) ratios displayed more robust correlations with FEV1% predicted value (r=0.741, p<0.01) and activation of effector T cells (r=-0.763, p<0.001).The imbalance between the anti-inflammatory subsets (aTreg+rTreg) and the pro-inflammatory subset (Fr III) of Tregs may play an important role in COPD progression.
Phenotype and suppressor activity of T-lymphocyte clones extracted from lesions of oral lichen planus
Authors: P.B. SUGERMAN, N.W. SAVAGE, G.J. SEYMOUR
Journal: British Journal of Dermatology (1994)

Lymphocytes were extracted from six biopsy specimens of oral lichen planus. T‐lymphocyte lines were expanded in culture with phytohaemagglutinin and interleukin 2, and cloned by limiting dilution. Fifteen T‐cell clones were isolated with a probability of clonality of 96.3%. The majority of clones (n=13) expressed the αβ T‐cell receptor, and of these, 11 were CD8+ and two were CD4+. Two clones were CD4− and CD8−, and expressed the γδ T‐cell receptor. The ability of these clones (effectors) to suppress concanavalin‐A‐stimulated proliferation of autologous lesional T‐cell lines (responders) was assessed. Maximum suppressor activity ranged from 17 to 100%. The majority of clones (n=12), including a CD3+ CD4+CD8−αβ+ clone, displayed suppressor activity which was proportional to the effector to responder ratio. A CD3+CD4+CD8−αβ+ clone and a CD3+CD4−CD8−γδ+ clone displayed substantial helper activity at higher effector to responder ratios. These results demonstrate differential helper and suppressor activity of T‐lymphocyte clones extracted from oral lichen planus lesions. The balance between help and suppression may be a fundamental determinant of immunological activity within the lymphocytic infiltrate of oral lichen planus, and hence may dictate the clinical behaviour of the disease.
Clinically relevant fatigue in cancer outpatients: the Edinburgh Cancer Centre symptom study
Authors: D.J. Storey, R.A. Waters, C.J. Hibberd, R.W. Rush, A.T. Cargill, L.R. Wall, M.T. Fallon, V.A. Strong, J. Walker, M. Sharpe
Journal: Annals of Oncology (2007)
Role of SIRT3 in the regulation of redox balance during oral carcinogenesis
Authors: I-Chieh Chen, Wei-Fan Chiang, Shyun-Yeu Liu, Pei-Fen Chen, Hung-Che Chiang
Journal: Molecular Cancer (2013)

Abstract Background Sirtuins (SIRT1-7) are a family of NAD-dependent deacetylases, which play an important role in regulating cancer tumorigenesis; however, their role in oral cancer has been controversial. SIRT3 is localized in the mitochondria, where it deacetylates and activates several enzymes involved in cellular redox balance and defense against oxidative damage. Results We found that compared with normal human oral keratinocytes (HOK), SIRT3 is highly expressed in oral squamous cell carcinoma (OSCC) cell lines, but the enzymatic deacetylation is significantly reduced. We also sequenced the entire coding region of SIRT3 and found the same mutation in 2 different OSCC cell lines. This point mutation is located in close proximity to the active site of deacetylase in the SIRT3 protein, and reduces the overall enzymatic efficiency of deacetylation. Furthermore, up-regulation of SIRT3 inhibited the cell growth of OSCCs and decreased the levels of basal reactive oxygen species (ROS) in both OSCC lines. To verify that the SIRT3 sequence variation was associated with oral carcinogenesis, we sequenced the SIRT3 gene from 21 OSCC patients, and 5 of the 21 patients (23.8%) carried the heterozygous missense mutation, p.Val208Ile. The heterozygous missense mutation in these patients was present in gremlin DNA isolated from both normal and tumor tissues. Conclusions Our findings provide a valuable insight into the potential role of SIRT3 in the development of oral squamous cell carcinoma, by showing that a non-synonymous point mutation in SIRT3 contributes to reduced catalytic activity of the protein and affects redox balance in OSCCs.
Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Kalliopi Pilichou, Andrea Nava, Cristina Basso, Giorgia Beffagna, Barbara Bauce, Alessandra Lorenzon, Gianfranco Frigo, Andrea Vettori, Marialuisa Valente, Jeffrey Towbin, Gaetano Thiene, Gian Antonio Danieli, Alessandra Rampazzo
Journal: Circulation (2006)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive myocardial atrophy with fibrofatty replacement. The recent identification of causative mutations in plakoglobin, desmoplakin (DSP), and plakophilin-2 (PKP2) genes led to the hypothesis that ARVC is due to desmosomal defects. Therefore, desmoglein-2 (DSG2), the only desmoglein isoform expressed in cardiac myocytes, was screened in subjects with ARVC.In a series of 80 unrelated ARVC probands, 26 carried a mutation in DSP (16%), PKP2 (14%), and transforming growth factor-beta3 (2.5%) genes; the remaining 54 were screened for DSG2 mutations by denaturing high-performance liquid chromatography and direct sequencing. Nine heterozygous DSG2 mutations (5 missense, 2 insertion-deletions, 1 nonsense, and 1 splice site mutation) were detected in 8 probands (10%). All probands fulfilled task force criteria for ARVC. An endomyocardial biopsy was obtained in 5, showing extensive loss of myocytes with fibrofatty tissue replacement. In 3 patients, electron microscopy investigation was performed, showing intercalated disc paleness, decreased desmosome number, and intercellular gap widening.This is the first investigation demonstrating DSG2 gene mutations in a significant number of ARVC-unrelated probands. Cardiac phenotype is characterized clinically by typical ARVC features with frequent left ventricular involvement and morphologically by fibrofatty myocardial replacement and desmosomal remodeling. The presence of mutations in desmosomal encoding genes in 40% of cases confirms that many forms of ARVC are due to alterations in the desmosome complex.
Learning in and about opaque worlds
Authors: Denis Tatone, Gergely Csibra
Journal: Behavioral and Brain Sciences (2015)

Abstract We argue that direct active teaching in humans exhibits at least two properties (open-endedness and content opacity) that make the recognition of teaching episodes without ostension untenable. Thus, while we welcome Kline's functional approach to the analysis of teaching, we think that she ignores important features of the socio-environmental niche in which human teaching likely evolved.
T Cell–Dependent Antibody Responses against Aberrantly Expressed Cyclin B1 Protein in Patients with Cancer and Premalignant Disease
Authors: Hiroyuki Suzuki, Daniel F. Graziano, John McKolanis, Olivera J. Finn
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclin B1–derived peptides were shown by us to be targets of tumor-specific CD8+ T cells in patients with breast and head and neck cancer. We obtained further evidence of cyclin B1 immunogenicity and its potential to serve as a tumor-specific antigen by analyzing its ability to elicit T cell–dependent humoral immune responses in vivo in patients with different types of tumors. Experimental Design: Recombinant cyclin B1 protein from two different sources was purified and used as antigen in ELISA assays to test sera from patients with breast, pancreatic, colon, and lung cancer for the presence of anti-cyclin B1 antibody. We also analyzed patients with benign lung disease, premalignant disease, and a known history of heavy smoking. Results and Conclusions: Cyclin B1 elicits helper T cell–dependent antibody responses in vivo. Tumors with higher level of cyclin B1 expression elicit higher anti-cyclin B1 antibody levels. Antibodies in patients with breast and colon cancer are primarily of the IgG isotype whereas patients with pancreatic and lung cancer have in addition anti-cyclin B1 IgA. Cyclin B1–specific IgG was also detected in long-term smokers and in patients with preneoplastic lung disease. Immune responses to aberrantly expressed cyclin B1 in tumors and premalignant lesions should be further explored as diagnostic and prognostic markers, in addition to their immunotherapeutic potential.
Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation
Authors: Katia Perruccio, Antonella Tosti, Emanuela Burchielli, Fabiana Topini, Loredana Ruggeri, Alessandra Carotti, Marusca Capanni, Elena Urbani, Antonella Mancusi, Franco Aversa, Massimo F. Martelli, Luigina Romani, Andrea Velardi
Journal: Blood (2005)
New Untwist on Diastole
Authors: Elyse Foster, Katy E. Lease
Journal: Circulation (2006)

iastolic dysfunction contributes significantly to the clinical syndrome of congestive heart failure in the settings of both preserved and impaired left ventricular (LV) systolic function. 1,2Over the past 20 years, the clinical diagnosis of diastolic dysfunction has been based largely on echocardiographic Doppler parameters of LV filling. 3The most important limitation of these parameters is their dependence on loading conditions.New practical and comprehensive methods of evaluating diastolic function are critically needed not only for diagnosis but also for testing emerging new therapies. Article p 2524Recent work has elucidated both intracellular and extracellular mechanisms that contribute to diastolic dysfunction, and some progress has been made in finding new treatments for diastolic heart failure.Additional research has evaluated the contribution of LV architecture and its role in maintaining the normal contraction sequence that optimizes mechanical efficiency.The importance of systolic twist and the subsequent recoil that leads to diastolic untwisting was examined in the article by Notomi et al 4 using tissue Doppler techniques in both normal subjects and patients with hypertrophic cardiomyopathy, at rest and during exercise.