tbuckley/cabot-search huggingface dataset:
Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cells
Authors: Rebekka Geiger, Thomas Duhen, Antonio Lanzavecchia, Federica Sallusto
Journal: The Journal of Experimental Medicine (2009)

The enormous diversity of the naive T cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides that bind to MHC molecules. The low frequency of antigen-specific naive T cells, their high activation threshold, and the constrains of antigen-processing and presentation have hampered analysis of naive repertoires to complex protein antigens. In this study, libraries of polyclonally expanded naive T cells were used to determine frequency and antigen dose–response of human naive CD4+ T cells specific for a variety of antigens and to isolate antigen-specific T cell clones. In the naive repertoire, T cells specific for primary antigens, such as KLH and Bacillus anthracis protective antigen, and for recall antigens, such as tetanus toxoid, cytomegalovirus, and Mycobacterium tuberculosis purified protein derivative, were detected at frequencies ranging from 5 to 170 cells per 106 naive T cells. Antigen concentrations required for half-maximal response (EC50) varied over several orders of magnitude for different naive T cells. In contrast, in the memory repertoire, T cells specific for primary antigens were not detected, whereas T cells specific for recall antigens were detected at high frequencies and displayed EC50 values in the low range of antigen concentrations. The method described may find applications for evaluation of vaccine candidates, for testing antigenicity of therapeutic proteins, drugs, and chemicals, and for generation of antigen-specific T cell clones for adoptive cellular immunotherapy.
Cancer induced bone pain
Authors: C. M. Kane, P. Hoskin, M. I. Bennett
Journal: BMJ (2015)

#### The bottom line

Bone pain is the most common type of pain from cancer and is present in around one third of patients with bone metastases.1 2 Based on postmortem studies of patients with advanced cancer and clinical knowledge of how often bone metastases result in pain, the incidence of cancer induced bone pain is estimated at 30 000 patients in the United Kingdom each year.3 w1 Currently, improvements in cancer treatments mean that many patients are living with metastatic cancer for several years. The prevalence of cancer induced bone pain is therefore likely to be much greater than the annual incidence.w1 Cancer induced bone pain is considered one of the most difficult pain conditions to treat because of its frequent association with weight bearing and movement. Not surprisingly, it has a major impact on patients’ daily functioning and mood and can result in admission to hospital.w2 w3

#### Sources and selection criteria

We searched Medline, Clinical Evidence, and the Cochrane Library using the terms “bone metastases”, “pain”, and “bone pain” and then combined these with the specific treatment terms individually. Where possible we have used systematic reviews but not referenced trials included in these reviews. We …
Retinal Blood Flow in Type 1 Diabetic Patients With No or Mild Diabetic Retinopathy During Euglycemic Clamp
Authors: Berthold Pemp, Elżbieta Polska, Gerhard Garhofer, Michaela Bayerle-Eder, Alexandra Kautzky-Willer, Leopold Schmetterer
Journal: Diabetes Care (2010)

To compare total retinal blood flow in diabetic patients with no or mild nonproliferative diabetic retinopathy and healthy control subjects and to investigate in patients whether there is a difference between retinal blood flow before morning insulin and under normoglycemic conditions using a glucose clamp.Twenty patients with type 1 diabetes with no or mild diabetic retinopathy were included in this open parallel-group study, and 20 healthy age- and sex-matched subjects were included as control subjects. Retinal blood flow was assessed by combining velocity measurements using laser Doppler velocimetry and diameter measurements using a commercially available dynamic vessel analyzer. Measurements were performed before and during a euglycemic clamp.Total retinal blood flow was higher in diabetic patients (53 +/- 16 microl/min) than in healthy subjects (43 +/- 16 microl/min; P = 0.034 between groups). When plasma glucose in diabetic patients was reduced from 9.3 +/- 1.7 to 5.3 +/- 0.5 mmol/l (P < 0.001) retinal blood flow decreased to 49 +/- 15 microl/min (P = 0.0003 vs. baseline). Total retinal blood flow during the glucose clamp was not significantly different from blood flow in normal control subjects (P = 0.161).Type 1 diabetic patients with no or only mild diabetic retinopathy have increased retinal blood flow before their morning insulin dosage. Blood flow is reduced toward normal during euglycemic conditions. Retinal blood flow may fluctuate significantly with fluctuating plasma glucose levels, which may contribute to the microvascular changes seen in diabetic retinopathy.
Patterns of fetal and infant growth are related to atopy and wheezing disorders at age 3 years
Authors: K. C. Pike, S. R. Crozier, J. S. A. Lucas, H. M. Inskip, S. Robinson, G. Roberts, K. M. Godfrey
Journal: Thorax (2010)

<h3>Background</h3> Little is known about whether patterns of early growth are associated with altered respiratory and immune development. This study relates prenatal and infant growth patterns to wheeze and atopy at age 3 years. <h3>Methods</h3> Birth weight and length were measured in 1548 children born at term. Conditional fetal head and abdominal circumference growth velocities were calculated from antenatal ultrasound measurements. Conditional postnatal growth velocities were calculated from infant weight, length and adiposity data. Measures of size and conditional growth were related to parentally-reported infant and early childhood wheeze and to atopic status at age 3 years. <h3>Results</h3> The risk of atopy increased by 46% per SD increase in abdominal circumference growth velocity from 11 to 19 weeks gestation but by 20% per SD decrease in abdominal growth velocity from 19 to 34 weeks (p=0.007 and p=0.011, respectively). The risk of atopic wheeze increased by 20% per SD decrease in 19–34-week abdominal growth (p=0.046). The risk of non-atopic wheeze increased by 10% per SD decrease in 11–19-week head circumference growth. Greater relative infant weight and adiposity gains were associated with both atopic and non-atopic wheeze. <h3>Conclusions</h3> A rapid growth trajectory during 11–19 weeks gestation followed by late gestation growth faltering is associated with atopy, suggesting that influences affecting fetal growth may also alter immune development. A lower early fetal growth trajectory is associated with non-atopic wheeze, possibly reflecting an association with smaller airways. An association between postnatal adiposity gain and wheeze may partly reflect prenatal influences that cause fetal growth to falter but are then followed by postnatal adiposity gain.
Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A
Authors: Marietta Herrmann, Cora Schäfer, Alexander Heiss, Steffen Gräber, Anne Kinkeldey, Andrea Büscher, Martin M.N. Schmitt, Jörg Bornemann, Falk Nimmerjahn, Martin Herrmann, Laura Helming, Siamon Gordon, Willi Jahnen-Dechent
Journal: Circulation Research (2012)

Fetuin-A is a liver-derived plasma protein involved in the regulation of calcified matrix metabolism. Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification.We studied CPP clearance in mice and in cell culture to identify the tissues, cells, and receptors involved in the clearance.In mice, fetuin-A-containing CPPs were rapidly cleared by the reticuloendothelial system, namely Kupffer cells of the liver and marginal zone macrophages of the spleen. Macrophages from scavenger receptor-AI/II (SR-A)-deficient mice cleared CPPs less efficiently than macrophages from wild-type mice, suggesting that SR-AI/II is involved in CPP binding and endocytosis. Accordingly, we found reduced clearance of CPPs in SR-A/MARCO-deficient mice.We could demonstrate that fetuin-A-containing CPPs facilitate the clearance of mineral debris by macrophages via SR-A. Since the same receptor also contributes to the uptake of modified low-density lipoprotein particles in atherosclerosis, defective endocytosis of both types of particle may impinge on lipid as well as mineral debris clearance in calcifying atherosclerosis.
Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma.
Authors: K Wallner, J Roy, L Harrison
Journal: Journal of Clinical Oncology (1996)

PURPOSE To quantify disease progression and morbidity following computer tomography (CT)-based transperineal iodine 125 prostate implantation. METHODS Ninety-two patients with clinical stage T1 or T2, Gleason score 2 to 7/10, prostatic carcinoma had outpatient, CT-based transperineal 125I prostate implantation and were monitored for 1 to 7 years (median, 3). The prescribed minimum radiation dose was 140 to 160 Gy. Lymph node dissection and postimplantation prostatic biopsies were not routinely performed. RESULTS In 46% of patients, radiation-related urinary symptoms were substantial enough at 1 month following implantation to require medication. Radiation-related urinary symptoms gradually resolved. Two years after implantation, 14% of patients had persistent urinary symptoms of Radiation Therapy Oncology Group (RTOG) &gt; or = grade 2. Eight percent of patients underwent a transurethral resection of the prostate (TURP) within 2 years of implantation. Five patients developed radiation-induced rectal ulcerations. Of 56 patients who were sexually potent preimplantation, 86% retained potency at 3 years. Twenty-five patients had biochemical disease progression. The overall actuarial freedom from biochemical failure rate at 4 years following implantation was 63%. In Cox proportional hazards multivariate analysis, the strongest predictor of failure was prostate-specific antigen (PSA) level less than or greater than 10 ng/mL (P = .005), followed by Gleason score (2 to 4 v 5 to 7, P = .08) and stage (T1 v T2, P = .09). CONCLUSION The 5-year biochemical freedom-from-progression rates following transperineal 125I implantation are comparable with those achieved with prostatectomy. The morbidity has decreased with increased physician experience.
Prolonged plasticity: Necessary and sufficient for language-ready brains
Authors: Patricia J. Brooks, Sonia Ragir
Journal: Behavioral and Brain Sciences (2008)

Abstract Languages emerge in response to the negotiation of shared meaning in social groups, where transparency of grammar is necessitated by demands of communication with relative strangers needing to consult on a wide range of topics (Ragir 2002). This communal exchange is automated and stabilized through activity-dependent fine-tuning of information-specific neural connections during postnatal growth and social development.
Category-specific deficits: Will a simpler model do?
Authors: Jules Davidoff
Journal: Behavioral and Brain Sciences (2001)

The purpose of the commentary is not to contradict HIT but rather to question whether its increase in predictive power outweighs the decrease in parsimony. For the refutable aspects of HIT, a simpler model for naming appears to achieve as much. Both models better fit the facts concerning naming performance than describe category-specificity.
Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling
Authors: A. Johnston, A.M. Guzman, W.R. Swindell, F. Wang, S. Kang, J.E. Gudjonsson
Journal: British Journal of Dermatology (2014)

Antitumour necrosis factor (anti-TNF)-α therapy has made a significant impact on the treatment of psoriasis. Despite these agents being designed to neutralize TNF-α activity, their mechanism of action in the resolution of psoriasis remains unclear.To understand better the mechanism of action of etanercept by examining very early changes in the lesional skin of patients with psoriasis responding to etanercept.Twenty patients with chronic plaque psoriasis were enrolled and received etanercept 50 mg twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by quantitative reverse-transcription polymerase chain reaction and microarray; cytokine and phosphoprotein levels were assessed using multiplexed bead arrays.In etanercept responders, we observed no significant changes in interleukin (IL)-17A, IL-22 or interferon-γ mRNA or protein in the first week of treatment; however, there was a 2·5-fold downregulation of IL-17 receptor C (IL-17RC) mRNA (P < 0·05) after day 1, accompanied by decreased extracellular signal-regulated kinase-1/2 phosphorylation. Transcriptional analysis revealed that genes suppressed by etanercept significantly overlapped with IL-17A-induced genes, and a marked overlap was also observed between the genes suppressed by etanercept and by the anti-IL-17A agent ixekizumab. Finally we show that TNF-α enhances the expression of IL-17RC, and short hairpin RNA inhibition of IL-17R expression abrogates synergistic gene induction by TNF and IL-17A.These results suggest that the early responses of psoriasis plaques to etanercept may be due to decreased tissue responsiveness to IL-17A due to suppressed IL-17RC expression in keratinocytes, blunting the strong synergy between TNF-α and IL-17, which contributes to the maintenance of psoriasis lesions.
Hyperparathyroidism and Medullary Sponge Kidney
Authors: Otto C. Beyer
Journal: JAMA (1977)

To the Editor.—  The article concerning the occurrence of hyperparathyroidism and medullary sponge kidney as presented by Gremillion et al (237:799, 1977) was of interest to me since I have a patient, a 50-year-old woman, who underwent excision of a parathyroid adenoma in April 1969. The intravenous pyelogram also disclosed the presence of brush-like appearance in the pyramidal portion of both kidneys, and this was thought to be consistent with medullary sponge kidneys. In addition, the patient has had numerous bouts of acute renal colic owing to the presence of a number of small calculi in both kidneys. The patient's serum calcium as well as urinary calcium levels have remained within normal limits since her surgery. Her parahormone level has also remained normal.  It interests me also that perhaps there is more than just a chance relationship between the occurrence of hyperparathyroid disease and medullary sponge kidney.
Normal hospital and low-bacterial diet in patients with cytopenia after intensive chemotherapy for hematological malignancy: a study of safety
Authors: F.H. van Tiel, M.M. Harbers, P.H.W. Terporten, R.T.C. van Boxtel, A.G. Kessels, GBWE Voss, H.C. Schouten
Journal: Annals of Oncology (2007)
Association of Wwox with ErbB4 in Breast Cancer
Authors: Rami I. Aqeilan, Valentina Donati, Eugenio Gaudio, Milena S. Nicoloso, Maria Sundvall, Anna Korhonen, Johan Lundin, Jorma Isola, Marius Sudol, Heikki Joensuu, Carlo M. Croce, Klaus Elenius
Journal: Cancer Research (2007)

WWOX, WW domain-containing oxidoreductase, is a tumor suppressor that is altered in many human cancers, including breast cancer. Wwox interacts with the ErbB4 receptor, reduces nuclear translocation of the cleaved intracellular domain of ErbB4, and inhibits its transactivation function mediated through Yes-associated protein. Here, we assessed the clinical significance of the Wwox-ErbB4 association. We determined Wwox protein expression by immunohistochemistry in a series of 556 breast cancers. Wwox expression was absent in 36% of the cancers, and loss of Wwox expression was associated with unfavorable outcome (P = 0.02). Membranous location of ErbB4 was associated with favorable survival compared with women whose cancer lacked such ErbB4 expression (P = 0.02). Wwox expression was strongly associated with membranous ErbB4 localization (P = 0.0003) and with overall ErbB4 expression (P = 0.0002). Coexpression of membranous ErbB4 and Wwox was associated with favorable outcome compared with cases with membranous ErbB4 and no Wwox immunoreactivity (P = 0.002). In vitro, Wwox associated with the two ErbB4 isoforms, JM-a CYT-1 and JM-a CYT-2, expressed in breast cancer. Moreover, expression of Wwox both in vitro and in vivo led to accumulation of total full-length membrane-associated ErbB4. These results suggest that expression of Wwox is associated with ErbB4 expression and that their coexpression has prognostic significance in breast cancer.
Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells
Authors: Francescopaolo Di Cello, V Lynn Flowers, Huili Li, Briana Vecchio-Pagán, Brent Gordon, Kirsten Harbom, James Shin, Robert Beaty, Wei Wang, Cory Brayton, Stephen B Baylin, Cynthia A Zahnow
Journal: Molecular Cancer (2013)

Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic mammary epithelial cells and breast cancer cells using in vitro and in vivo models of chronic cigarette smoke exposure.We show that both non-tumorigenic (MCF 10A, MCF-12A) and tumorigenic (MCF7) breast epithelial cells exposed to cigarette smoke acquire mesenchymal properties such as fibroblastoid morphology, increased anchorage-independent growth, and increased motility and invasiveness. Moreover, transplantation experiments in mice demonstrate that treatment with cigarette smoke extract renders MCF 10A cells more capable to survive and colonize the mammary ducts and MCF7 cells more prone to metastasize from a subcutaneous injection site, independent of cigarette smoke effects on the host and stromal environment. The extent of transformation and the resulting phenotype thus appear to be associated with the differentiation state of the cells at the time of exposure. Analysis by flow cytometry showed that treatment with CSE leads to the emergence of a CD44(hi)/CD24(low) population in MCF 10A cells and of CD44+ and CD49f + MCF7 cells, indicating that cigarette smoke causes the emergence of cell populations bearing markers of self-renewing stem-like cells. The phenotypical alterations induced by cigarette smoke are accompanied by numerous changes in gene expression that are associated with epithelial to mesenchymal transition and tumorigenesis.Our results indicate that exposure to cigarette smoke leads to a more aggressive and transformed phenotype in human mammary epithelial cells and that the differentiation state of the cell at the time of exposure may be an important determinant in the phenotype of the final transformed state.
Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial
Authors: Raphaèle Seror, Gabriel Baron, Eric Hachulla, Michel Debandt, Claire Larroche, Xavier Puéchal, François Maurier, Benoît de Wazieres, Thomas Quéméneur, Philippe Ravaud, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the effect of adding a 10-week treatment of adalimumab to a standardised treatment with corticosteroids on the ability to taper more rapidly corticosteroid doses in patients with newly diagnosed giant cell arteritis (GCA). <h3>Methods</h3> Patients included in this double-blind, multicentre controlled trial were randomly assigned to receive a 10-week subcutaneous treatment of adalimumab 40 mg every other week or placebo in addition to a standard prednisone regimen (starting dose 0.7 mg/kg per day). The primary endpoint was the percentage of patients in remission on less than 0.1 mg/kg of prednisone at week 26. Analysis was performed by intention to treat (ITT). <h3>Results</h3> Among the 70 patients enrolled (adalimumab, n=34; placebo, n=36), 10 patients did not receive the scheduled treatment, seven in the adalimumab and three in the placebo group. By ITT, the number of patients achieving the primary endpoint was 20 (58.9%) and 18 (50.0%) in the adalimumab and placebo arm, respectively (p=0.46). The decrease in prednisone dose and the proportion of patients who were relapse free did not differ between the two groups. Serious adverse events occurred in five (14.7%) patients on adalimumab and 17 (47.2%) on placebo, including serious infections in three patients on adalimumab and five on placebo. Two patients died in the placebo arm (septic shock and cancer) and one in the adalimumab group (pneumonia). <h3>Conclusions</h3> In patients with newly diagnosed GCA, adding a 10-week treatment of adalimumab to prednisone did not increase the number of patients in remission on less than 0.1 mg/kg of corticosteroids at 6 months. <h3>Clinical trial registration number</h3> NCT00305539.
Stability of COPD phenotypes over time
Authors: Judith Garcia-Aymerich, Marta Benet, Josep M. Antó
Journal: European Respiratory Journal (2012)

Three phenotypes (severe respiratory, moderate respiratory, and systemic COPD) were previously identified by cluster analysis in COPD patients, which differed in clinical expression and outcomes (Garcia-Aymerich 2011, Thorax). Aim: To study the stability of these phenotypes over time. Methods: 251 COPD patients from the PAC-COPD study participated in a follow-up visit a mean of 1.7 years after their baseline assessment. Symptoms, lifestyle, comorbidities, quality of life, body mass and composition, complete lung function, muscle function, 6-min walking test, and serum inflammatory biomarkers were measured. Patients were grouped according to the distribution of 104 variables (phenotypic traits) using partitioning cluster analysis (kmeans). Results: Two or three groups were suggested as the best clustering statistical alternatives, and three groups were clinically more meaningful. Group 1 (n=116 (46%), 69 y) included patients with worse airflow limitation, hyperinflation, and impaired gas exchange; patients in Group 2 (n=108 (43%), 70 y) exhibited better health in all domains; Group 3 (n=27 (8%), 74 y) had a higher prevalence of respiratory symptoms, worse quality of life, impaired exercise capacity and muscle strength, and a higher proportion of co-morbidities. The baseline “severe respiratory” group mostly fell (91%) in follow-up Group 1; 25% and 70% of patients in baseline “moderate respiratory” belonged to follow-up Group 1 and 2, respectively; patients in baseline “systemic” phenotype were distributed across all phenotypes but represented 70% of follow-up Group 3. Conclusion: The three phenotypes identified in the follow-up visit exhibit very similar clinical characteristics than the baseline ones. Most patients remain in the same group.