tbuckley/cabot-search huggingface dataset:
Regulatory functions of CD8+CD28– T cells in an autoimmune disease model
Authors: Nader Najafian, Tanuja Chitnis, Alan D. Salama, Bing Zhu, Christina Benou, Xueli Yuan, Michael R. Clarkson, Mohamed H. Sayegh, Samia J. Khoury
Journal: Journal of Clinical Investigation (2003)

CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, CD8–/–CD28–/– double-knockout mice are susceptible to EAE. These findings suggest a role for CD8+ T cells in the resistance of CD28-deficient mice to disease. Adoptive transfer of CD8+CD28– T cells into CD8–/– mice results in significant suppression of disease, while CD8+CD28+ T cells demonstrate no similar effect on the clinical course of EAE in the same recipients. In vitro, CD8+CD28– but not CD8+CD28+ T cells suppress IFN-γ production of myelin oligodendrocyte glycoprotein–specific CD4+ T cells. This suppression requires cell-to-cell contact and is dependent on the presence of APCs. APCs cocultured with CD8+CD28– T cells become less efficient in inducing a T cell–dependent immune response. Such interaction prevents upregulation of costimulatory molecules by APCs, hence decreasing the delivery of these signals to CD4+ T cells. These are the first data establishing that regulatory CD8+CD28– T cells occur in normal mice and play a critical role in disease resistance in CD28–/– animals.
Neoadjuvant Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With Pegfilgrastim Support in Muscle-Invasive Urothelial Cancer: Pathologic, Radiologic, and Biomarker Correlates
Authors: Toni K. Choueiri, Susanna Jacobus, Joaquim Bellmunt, Angela Qu, Leonard J. Appleman, Christopher Tretter, Glenn J. Bubley, Edward C. Stack, Sabina Signoretti, Meghara Walsh, Graeme Steele, Michelle Hirsch, Christopher J. Sweeney, Mary-Ellen Taplin, Adam S. Kibel, Katherine M. Krajewski, Philip W. Kantoff, Robert W. Ross, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2014)

In advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscle-invasive urothelial cancer (MIUC).
‘A no means no’—measuring depression using a single-item question versus Hospital Anxiety and Depression Scale (HADS-D)
Authors: J. Skoogh, N. Ylitalo, P. Larsson Omeróv, A. Hauksdóttir, U. Nyberg, U. Wilderäng, B. Johansson, M. Gatz, G. Steineck
Journal: Annals of Oncology (2010)
Identifying needs and opportunities for advancing translational research in cardiovascular disease
Authors: K. R. Sipido, A. Tedgui, S. D. Kristensen, G. Pasterkamp, H. Schunkert, M. Wehling, P. G. Steg, W. Eisert, F. Rademakers, B. Casadei, V. Fuster, E. Cerbai, G. Hasenfuss, F. Fernandez-Aviles, D. Garcia-Dorado, M. Vidal, M. Hallen, V. Dambrauskaite
Journal: Cardiovascular Research (2009)

In Western Europe, as in the USA, mortality of cardiovascular disease (CVD) has declined significantly in the last 30 years. Life expectancy for patients with coronary heart disease in the USA increased on average by 3 years between 1970 and 2000.1 Several epidemiological analyses support this positive evolution. An analysis of the underlying causes identifies improvements in quality of care and treatment as a major cause, accounting from 50 up to 75% of the success depending on the study samples, the remainder being accounted for by changes in lifestyle and prevention.2 Research and development in several areas of CVD have contributed to this success. In acute coronary events, the identification and development of efficient and safe thrombolytic agents followed by percutaneous coronary intervention with stent implantation were milestones in the reduction of acute mortality and salvage of myocardium.3–5 Statins have brought a major advance in preventing the progression of atherosclerotic disease and have been recognized for their wide mode of action.6 In heart failure (HF), beta-blockers and ACE-inhibitors have increased life expectancy by a leap.7 Some of these improvements have been the result of a classic bench-to-bedside development of a targeted treatment, such as the statins, others have known a more serendipitous development, such as beta-blockers.

In other areas, progress in terms of treatment has been less spectacular and fraught with difficulties. Development of antiarrhythmic agents received a large boost from basic insights into cardiac ion channel structure and function, but translation into pharmacology unveiled unexpected pro-arrhythmia risks of some of the highly specific ion channel blockers in class III.8 Automatic defibrillators have taken an important role in the treatment of life-threatening arrhythmias and save lives, but are not without burden and come at a high cost.9

This latter example is …
PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice
Authors: Mei Tran, Denise Tam, Amit Bardia, Manoj Bhasin, Glenn C. Rowe, Ajay Kher, Zsuzsanna K. Zsengeller, M. Reza Akhavan-Sharif, Eliyahu V. Khankin, Magali Saintgeniez, Sascha David, Deborah Burstein, S. Ananth Karumanchi, Isaac E. Stillman, Zoltan Arany, Samir M. Parikh
Journal: Journal of Clinical Investigation (2011)

Sepsis-associated acute kidney injury (AKI) is a common and morbid condition that is distinguishable from typical ischemic renal injury by its paucity of tubular cell death. The mechanisms underlying renal dysfunction in individuals with sepsis-associated AKI are therefore less clear. Here we have shown that endotoxemia reduces oxygen delivery to the kidney, without changing tissue oxygen levels, suggesting reduced oxygen consumption by the kidney cells. Tubular mitochondria were swollen, and their function was impaired. Expression profiling showed that oxidative phosphorylation genes were selectively suppressed during sepsis-associated AKI and reactivated when global function was normalized. PPARγ coactivator-1α (PGC-1α), a major regulator of mitochondrial biogenesis and metabolism, not only followed this pattern but was proportionally suppressed with the degree of renal impairment. Furthermore, tubular cells had reduced PGC-1α expression and oxygen consumption in response to TNF-α; however, excess PGC-1α reversed the latter effect. Both global and tubule-specific PGC-1α-knockout mice had normal basal renal function but suffered persistent injury following endotoxemia. Our results demonstrate what we believe to be a novel mechanism for sepsis-associated AKI and suggest that PGC-1α induction may be necessary for recovery from this disorder, identifying a potential new target for future therapeutic studies.
Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children
Authors: I. Heier, K. Malmstrom, A. Sajantila, J. Lohi, M. Makela, F. L. Jahnsen
Journal: Thorax (2010)

Childhood represents an immunological window of vulnerability in which individuals are at increased risk for both serious infections and development of allergic diseases, particularly affecting the airways. However, little is known about how the airway mucosal immune system is organised and functions during early age. Here, the organisation of immune cells in bronchial mucosa of children was characterised.Immunophenotyping was performed on mucosal samples obtained postmortem from nine children aged 2-15&emsp14;years without any history of atopic manifestations or any signs of respiratory disease, who died from non-inflammatory causes.In all nine cases, isolated lymphoid follicles (ILFs), interpreted as bronchus-associated lymphoid tissue (BALT), were found, constituting an average frequency of 60 ILFs/cm(2) of airway mucosal surface. Outside these ILFs, dense networks of CD11c(+) myeloid dendritic cells (DCs), CD68(+) macrophages and CD3(+)CD45RA(-) memory T cells were found. Plasmacytoid DCs occurred in low numbers. Importantly, intraepithelial antigen-presenting cells were found to extend cellular projections into the airway lumen.The density and location of antigen-presenting cells and T cells in this age group are similar to those observed in adults. However, in contrast to adults, BALT appears to be a normal feature of the airway mucosa throughout childhood, suggesting that these structures contribute to regional immunity and homeostasis. This indicates that the local immune system in the airways of children has unique features which should be taken into account, not only when studying airway immunology and immunopathology, but also in the development of mucosal vaccines.
Caval Penetration by Inferior Vena Cava Filters
Authors: Zhongzhi Jia, Alex Wu, Mathew Tam, James Spain, J. Mark McKinney, Weiping Wang
Journal: Circulation (2015)

Limited penetration into the caval wall is an important securing mechanism for inferior vena cava (IVC) filters; however, caval penetration can also cause unintentional complications. The aim of this study was to assess the incidence, severity, clinical consequences, and management of filter penetration across a range of commercially available IVC filters.The MEDLINE database was searched for all studies (1970-2014) related to IVC filters. A total of 88 clinical studies and 112 case reports qualified for analysis; these studies included 9002 patients and 15 types of IVC filters. Overall, penetration was reported in 19% of patients (1699 of 9002), and 19% of those penetrations (322 of 1699) showed evidence of organ/structure involvement. Among patients with penetration, 8% were symptomatic, 45% were asymptomatic, and 47% had unknown symptomatology. The most frequently reported symptom was pain (77%, 108 of 140). Major complications were reported in 83 patients (5%). These complications required interventions including surgical removal of the IVC filter (n=63), endovascular stent placement or embolization (n=11), endovascular retrieval of the permanent filter (n=4), and percutaneous nephrostomy or ureteral stent placement (n=3). Complications led to death in 2 patients. A total of 87% of patients (127 of 146) underwent premature filter retrieval or interventions for underlying symptoms or penetration-related complications.Caval penetration is a frequent but clinically underrecognized complication of IVC filter placement. Symptomatic patients accounted for nearly 1/10th of all penetrations; most of these cases had organ/structure involvement. Interventions with endovascular retrieval and surgery were required in most of these symptomatic patients.
Association of the CTLA-4 Gene 49 A/G Polymorphism With Type 1 Diabetes and Autoimmune Thyroid Disease in Japanese Children
Authors: Mie Mochizuki, Shin Amemiya, Kisho Kobayashi, Koji Kobayashi, Yoshie Shimura, Toshihide Ishihara, Yoshiko Nakagomi, Kazumichi Onigata, Shinya Tamai, Akira Kasuga, Shinpei Nanazawa
Journal: Diabetes Care (2003)

OBJECTIVE—To clarify the role of the T-lymphocyte–associated-4 (CTLA-4) polymorphism in the susceptibility to child-onset type 1 diabetes with regard to its clinical characteristics and complications with autoimmune thyroid disease (AITD) in the Japanese population. RESEARCH DESIGN AND METHODS—The CTLA-4 49 A/G polymorphism was detected by the PCR-restriction fragment–length polymorphism (RFLP) method in 97 type 1 diabetic subjects and 20 patients with Graves’ disease, a cohort which included 4 patients who also had type 1 diabetes. RESULTS—The genotypes and allele frequencies of this polymorphism did not differ between the type 1 diabetic subjects and the control subjects. The G allele frequency was 63.9% in the type 1 diabetic subjects. The G allele frequency in the subgroup of patients with a high titer of autoantibodies to the GAD antibody (Ab) was 72.9% (P = 0.0499 vs. control subjects); in the subgroup of patients without HLA DRB1*0405, it was 72.6% (P = 0.0271 vs. control subjects); and in the subgroup of patients with a residual β-cell function, it was 78.6% (P = 0.0391 vs. control subjects). The G allele frequency in the patients with Graves’ disease was also significantly higher at 78.1% (P = 0.0405 vs. control subjects). Furthermore, the frequency in our diabetic subjects complicated with Graves’ disease was even higher (87.5%). CONCLUSIONS—We have demonstrated that a distinct association exists between the G allele of CTLA-4 and high values of GAD Ab, residual β-cell function, and the absence of HLA-DRB1*0405.
Herbal dietary supplement: continuing to explore cardiovascular protection
Authors: T. Tsuruda
Journal: Cardiovascular Research (2010)

This editorial refers to ‘EGb761 ameliorates the formation of foam cells by regulating the expression of SR-A and ABCA1: role of haem oxygenase-1’ by J.-Y. Tsai et al. , pp. 415–423, this issue. 

The initial step of atherogenesis is the development of so-called ‘fatty streaks,’ which are small, subendothelial deposits of monocyte-derived macrophages. Both the dysregulation of modified lipoprotein uptake and cholesterol efflux in macrophages play an important role in the pathogenesis.1 Macrophage scavenger receptors, such as type A scavenger receptor (SR-A) and CD36, mediate foam cell formation by facilitating the uptake of modified lipids.2 On the other hand, reverse cholesterol transport is the primary mechanism by which high-density lipoprotein and its major protein, apolipoprotein A-I, protect against atherosclerosis. Specifically, ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux from macrophages to lipid-free apolipoprotein A-I.3 Any effective treatments for inhibiting the uptake of modified lipoproteins and/or enhancing cholesterol efflux are considered important anti-atherosclerotic drugs to prevent or delay the onset of cardiovascular events.4

Ginkgo biloba is a deciduous tree that has survived unchanged for around 150 million years. The fruits and seeds of the G. biloba tree have been used in traditional Chinese medicine for over 5000 years, whereas Ginkgo leaves began to be used much later for skin … 

*Corresponding author. Tel: +81 985 85 0872; fax: +81 985 85 6596, Email: ttsuruda{at}med.miyazaki-u.ac.jp
The prevalence and incidence of cholecystolithiasis in patients with chronic liver diseases: A prospective study
Authors: I-Shyan Sheen, Yun-Fan Liaw
Journal: Hepatology (1989)

To investigate the prevalence and incidence of cholecystolithiasis in hepatitis B surface antigen-positive chronic liver diseases, a prospective study using hepatobiliary ultrasonography was conducted in 933 “healthy” persons and four groups of HBsAg-positive patients: 226 asymptomatic carriers, 73 patients with chronic active hepatitis, 77 patients with early liver cirrhosis and 124 patients with advanced liver cirrhosis. Patients with hepatocellular carcinoma or alcoholism were excluded. The prevalences of cholecystolithiasis increased along with the increasing duration and severity of chronic liver diseases, with a significant linear trend (p &lt; 0.001). The prevalences of cholecystolithiasis in patients with liver cirrhosis (18.5% in males, 31.2% in females) were 4 to 5.5 times higher than that of the healthy population (p &lt; 0.005). In addition, the linear trend of increasing prevalence with increasing age in the healthy population was not observed in patients with chronic liver diseases. On the other hand, five of the 69 patients with early liver cirrhosis were found to develop cholecystolithiasis during a mean follow-up period of 32 months. The calculated annual incidence of cholecystolithiasis was 2.6%. The results suggest that chronic liver disease, particularly liver cirrhosis, is a risk factor for cholecystolithiasis.
Effects of Urinary Macromolecules on Hydroxyapatite Crystal Formation
Authors: ANN M. BESHENSKY, JEFFREY A. WESSON, ELAINE M. WORCESTER, ELENA J. SOROKINA, CARL J. SNYDER, JACK G. KLEINMAN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Particle size analysis was combined with titration data obtained in constant-composition, hydroxyapatite (HA)-seeded, crystal growth assays. With addition of large amounts of HA (250 μg), titration rates were linear, new crystal formation was minimal, and aggregation effects could be detected. With addition of small amounts of HA (62.5 μg), nucleation of new HA was observed. The effects of urinary macromolecules, i.e., osteopontin (OPN), recombinant glutathione-S-transferase-OPN (G-OPN), Tamm-Horsfall protein, chondroitin sulfate, human serum albumin, mixed urinary macromolecules from a stone-former (SFU1), mixed urinary macromolecules from a normal individual (NU1), and polyaspartic acid (PA), were examined in this system. Crystal growth inhibition, as measured by the slope of linear titration curves in this system, was observed with PA, G-OPN, OPN, SFU1, and NU1. All of the macromolecules tested inhibited aggregation, including Tamm-Horsfall protein, which did not inhibit growth. As reflected by the ratio of the final number of particles to the initial number in the 62.5-μg seed addition, the macromolecules that were most effective in inhibiting growth, i.e., OPN, G-OPN, PA, SFU1, and NU1, actually increased secondary nucleation. Recombinant G-OPN demonstrated less inhibitory activity than did OPN isolated from cell culture. Chondroitin sulfate and human serum albumin exhibited no significant effects on the various components of HA crystallization under these conditions. SFU1 and NU1 slowed growth and increased secondary nucleation to similar degrees, and neither exhibited any measurable effect on aggregation. Therefore, crystal surface sites that participate in nucleation, growth, and aggregation processes are affected independently by macromolecules, presumably because of differences in their structural features. These results illustrate the utility of combining these techniques to provide a much greater understanding of crystallization behavior than that possible with either analysis alone.
Quality of Randomized Controlled Trials Reporting in the Primary Treatment of Brain Tumors
Authors: Rose Lai, Rong Chu, Michael Fraumeni, Lehana Thabane
Journal: Journal of Clinical Oncology (2006)

To assess the reporting quality of randomized controlled trials (RCTs) in the primary treatment of brain tumors and to identify significant predictors of quality.Two investigators searched MEDLINE, EMBASE, and bibliographies of retrieved articles for RCTs in the primary treatment of brain tumors published between January 1990 and December 2004. We assessed the quality of overall reporting and key methodologic factors reporting (allocation concealment, blinding, and intention to treat [ITT]). Two investigators also rated articles independently using items from the revised Consolidated Standards of Reporting Trials statement. A generalized estimated equation was used to generate regression models that identified significant factors associated with quality of reporting.We retrieved 74 relevant RCTs that randomly assigned 14,498 brain tumor patients. The quality of overall reporting has improved during the last 15 years, but eight of the 15 methodologic items were reported in less than 50% of trials. In the appraisal of the reporting quality of key methodologies, allocation concealment, blinding, and adherence to the ITT principle were reported in less than 30% of articles. Multivariable regression models revealed that an impact factor more than 1.66, publication after 1995, and sample size more than 280 were significant factors associated with better overall reporting, whereas complete industrial funding, impact factors more than 2.64, and positive primary outcomes were predictors of higher ratings of the three most important methodologic qualities.Despite improvement in general reporting quality, key methodologies that safeguard against biases may still benefit from better description. Significant factors associated with better reporting may act as surrogates for other characteristics.
Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging
Authors: Melissa N. McCracken, Dimitrios N. Vatakis, Dhaval Dixit, Jami McLaughlin, Jerome A. Zack, Owen N. Witte
Journal: Journal of Clinical Investigation (2015)

Adoptive transfer of tumor-reactive T cells can successfully reduce tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported. A noninvasive method to track engineered cells with high sensitivity and resolution would allow observation of correct cell homing and/or identification of dangerous off-target locations in preclinical and clinical applications. Human deoxycytidine kinase triple mutant (hdCK3mut) is a nonimmunogenic PET reporter that was previously shown to be an effective tool to monitor whole-body hematopoiesis. Here, we engineered a construct in which hdCK3mut is coexpressed with the anti-melanoma T cell receptor F5, introduced this construct into human CD34 cells or PBMCs, and evaluated this approach in multiple immunotherapy models. Expression of hdCK3mut allowed engrafted cells to be visualized within recipient bone marrow, while accumulation of [18F]-L-FMAU in hdCK3mut-expressing T cells permitted detection of intratumoral homing. Animals that received T cells coexpressing hdCK3mut and the anti-melanoma T cell receptor had demonstrably higher signals in HLA-matched tumors compared with those in animals that received cells solely expressing hdCK3mut. Engineered T cells caused cytotoxicity in HLA/antigen-matched tumors and induced IFN-γ production and activation. Moreover, hdCK3mut permitted simultaneous monitoring of engraftment and tumor infiltration, without affecting T cell function. Our findings suggest that hdCK3mut reporter imaging can be applied in clinical immunotherapies for whole-body detection of engineered cell locations.
Chemical modification of nuclear proteins by erythropoietin
Authors: Jerry L. Spivak, Lorna Peck
Journal: American Journal of Hematology (1979)

Abstract The spleen of the exhypoxic polycythemic mouse was employed as a model system to study the effect of erythropoietin on enzymes that chemically modify nuclear proteins. At selected time intervals after in vivo administration of erythropoietin, acetyltransferase and methyltransferase activity were measured in nuclei isolated from the spleens of treated mice. In addition, the incorporation of labeled methyl and acetate groups into individual histone proteins was also examined. A 36% increase in nuclear acetyltransferase activity was observed eight hours after administration of erythropoietin, whereas nuclear methyltransferase activity increased by 42% 24 hours after administration of the hormone. Selective acetylation or methylation of individual histone proteins was not observed, and it is concluded that activation of transcription by erythropoietin is not the result of acetylation or methylation of nuclear proteins.
Meningeal dissemination in primary CNS lymphoma: diagnosis, treatment, and survival in a large monocenter cohort
Authors: P. Kiewe, L. Fischer, P. Martus, E. Thiel, A. Korfel
Journal: Neuro-Oncology (2010)

The frequency of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL), its prognostic impact, and optimal management have not been defined thus far. In 69 of 92 (75%) immunocompetent patients, primarily diagnosed with PCNSL at our institution between January 1994 and February 2007, cerebrospinal fluid was analyzed for MD. MD was found by cytomorphology in 7/63 (11%), by immunophenotyping in 1/32 (3%), and by PCR of the IgH CDR III region in 6/37 (16%). Neuroradiologic examination revealed MD in 3 of 69 patients (4%). Median event-free survival (EFS) of patients with MD diagnosed by any of the methods was 26 months, of those without MD 34.1 months (P = .24); median overall survival (OAS) of these two patients' groups was 45.5 and 42.5 months, respectively (P = .34). Patients with cytomorphologic proof of MD had a median EFS of 15.4 months and OAS of 18.5 months, those without MD 34.3 and 45 months (P = .018 and .017, respectively). We found a low frequency of MD despite the use of putatively sensitive diagnostic methods. No impact on outcome was seen for MD, diagnosed by any of the methods used; however, patients with cytomorphologic proof of MD had a significantly shorter median EFS and OAS.