tbuckley/cabot-search huggingface dataset:
Reversal of Myeloid Cell–Mediated Immunosuppression in Patients with Metastatic Renal Cell Carcinoma
Authors: Sergei Kusmartsev, Zhen Su, Axel Heiser, Jens Dannull, Evgeniy Eruslanov, Hubert Kübler, Donna Yancey, Philip Dahm, Johannes Vieweg
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Tumor-induced immunosuppression remains a significant obstacle that limits the efficacy of biological therapy for renal cell carcinoma. Here we evaluate the role of CD33 myeloid-derived suppressor cells (MDSC) in the regulation of T-cell responses in renal cell carcinoma patients. We also examine effect of all-trans-retinoic acid (ATRA) on MDSC-mediated immune suppression. Experimental Design: CD33-positive myeloid cells were isolated from the peripheral blood of renal cell carcinoma patients with magnetic beads and tested in vitro for their ability to inhibit T-cell responses. T-cell function was evaluated using ELISPOT and CTL assays. Results: MDSC isolated from renal cell carcinoma patients, but not from healthy donors, were capable of suppressing antigen-specific T-cell responses in vitro through the secretion of reactive oxygen species and nitric oxide upon interaction with CTL. MDSC-mediated immune suppression and IFN-γ down-regulation was reversible in vitro by exposing cells to the reactive oxygen species inhibitors. Moreover, ATRA was capable of abrogating MDSC-mediated immunosuppression and improving T-cell function by direct differentiation into antigen-presenting cell precursors. Conclusions: These results may have significant implications regarding the future design of active immunotherapy protocols that may include differentiation agents as part of a multimodal approach to renal cell carcinoma immunotherapy.
Respiratory muscle strength and peak cough flow in patients with Parkinson's disease
Authors: Ana Paula Gama Vieira, Amanda Trentini Barbosa, Cristiely Ribas Padilha, Jean Felipe Baptistim, Silvia Valderramas
Journal: European Respiratory Journal (2013)

Background: Respiratory muscle weakness and decreased cough capacity are the main causes of pulmonary complications that result in morbidity and mortality in patients with Parkinson’s disease (PD).

Aim: to evaluate the respiratory muscle strength and peak cough flow in patients with Parkinson’s disease and determine if there is an association with the stage, symptoms and duration of the disease.

Methods: In a cross-sectional study, we evaluated 107 patients with PD (65,43±9,47 years) with Hoehn and Yahr stages I-III, and 107 healthy participants (65,32±9,34 years). Were measured the maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and peak cough flow (PCF) by a peak flow-meter. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr scale were employed to analyze the symptoms and stages of the disease respectively.

Results: The PD group showed an impairment of the MIP cmH2O (71,16±43,45 vs 89,72±33,03, p<0,01), MEP cmH2O (80,60±33,52 vs 107,88±41,25, p<0,01), PCF l/s (425,14±160,78 vs 481,74±148,28, p<0,01) than control group. There was a correlation between MIP and PCF (r=0,57, p<0,01), MIP and MEP (r=0,75, p<0,01) and MIP and symptoms (r=-0,21, p<0,01).

Conclusion: The patients with PD showed decreased respiratory muscle strength, peak cough flow and these parameters were correlated with the symptoms of the disease.
Cosmeceuticals: coming of age
Authors: T W Griffiths
Journal: British Journal of Dermatology (2010)

Journal Article Cosmeceuticals: coming of age Get access T.W. Griffiths T.W. Griffiths Department of Dermatology, University of Manchester, Manchester, U.K. and Macclesfield District General Hospital, Macclesfield SK10 3BL, U.K. E‐mail: tamara.griffiths@echeshire‐tr.nwest.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 3, 1 March 2010, Pages 469–470, https://doi.org/10.1111/j.1365-2133.2010.09634.x Published: 01 March 2010
Gemtuzumab ozogamicin, citosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia
Authors: L. Fianchi, L. Pagano, F. Leoni, S. Storti, M.T. Voso, C.G. Valentini, S. Rutella, A. Scardocci, M. Caira, G. Gianfaldoni, G. Leone
Journal: Annals of Oncology (2007)
Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease
Authors: Stephen MacMahon, Norman Sharpe, Greg Gamble, Alison Clague, Cliona Ni Mhurchu, Taane Clark, Hamish Hart, John Scott, Harvey White
Journal: Journal of the American College of Cardiology (2000)
One Cytokine, Two Isotypes
Authors: DONATA VERCELLI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

You can’t do it all. This is probably the reason why for a long time researchers interested in IgE regulation paid little attention to other immunoglobulin (Ig) isotypes and to the conditions required for their production. The discovery that isotype switching is directed by cytokines (reviewed in References 1 and 2), and that interleukin 4 (IL-4) is specifically responsible for the induction of switching to IgE (3), spurred a vast effort to try and understand the cellular and molecular mechanisms underlying the effects of this cytokine. In article after article (ours included) the leitmotif in the studies of IL-4-dependent IgE regulation was the specificity of the effects of this cytokine, that is, how IL-4 secures the production of IgE, and only IgE. One cytokine, one isotype. Molecular studies of the IgE system made a major contribution to the identification of germline transcription as a key step in determining the isotype specificity of switching. The expression of germline transcripts reflects the cytokine-dependent activation of transcription from an I H region located upstream of the switch region subsequently targeted by recombination (4, 5). The germline proceed from the I H region through the switch region itself and then all the way through the Ig constant heavy chain (C H ) gene expressed as a result of switching. The germline transcripts produced after splicing contain the I H region directly joined to the C H transcript (reviewed in Reference 1). It is by now generally accepted that processed germline transcripts and/or the mechanism of germline transcription are required to increase the accessibility of chromatin at a specific switch region (the one through which transcription is activated by the cytokine), which thus becomes the preferred target for the recombination machinery (6). Even though this model awaits direct confirmation (7), it is strongly supported by an overwhelming amount of data from different experimental systems, first and foremost mice in which genes essential for germline transcription have been deleted by homologous recombination (8–14).
Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection
Authors: Sungchul Kim, Daekwan Seo, Dongwoo Kim, Yujin Hong, Hyeshik Chang, Daehyun Baek, V. Narry Kim, Sungwook Lee, Kwangseog Ahn
Journal: Cell Host & Microbe (2015)
Telomerase activity as a biomarker for (pre)neoplastic cervical disease in scrapings and frozen sections from patients with abnormal cervical smear.
Authors: G B Wisman, H Hollema, S de Jong, J ter Schegget, S P Tjong-A-Hung, M H Ruiters, M Krans, E G de Vries, A G van der Zee
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the diagnostic value of semi-quantitative telomerase activity assessment in cervical scrapings together with human papillomavirus (HPV) typing for detection of (pre)neoplastic cervical lesions and to compare telomerase activity in cervical scrapings and frozen specimens from the same patients. PATIENTS AND METHODS A cross-sectional study was performed in 161 patients referred for an abnormal cervical cytology report. In cervical scrapings, telomerase activity was determined by modified telomere repeat amplification protocol (TRAP) assay and HPV typing by polymerase chain reaction (PCR) with general and type-specific primers. Final diagnosis was made by pathologic examination of biopsy and/or loop excision specimens. RESULTS Telomerase activity was detectable in assessable scrapings from one of nine (11%) patients without cervical intraepitheleal neoplasia (CIN), in three of 26 (12%) with CIN I, eight of 35 (22%) with CIN II, 18 of 62 (29%) with CIN III, and four of 13 (31%) with cancer. Sensitivity and negative predictive value of the TRAP assay for CIN II/III and cancer lesions were 25% and 28%, respectively, while specificity for no CIN or CIN I was 89%. In representative frozen sections, frequency of detectable telomerase activity was related to grade of CIN/cancer; none of 21 normal cervices, none of two CIN I, two of 12 (17%) CIN II, 10 of 31 (32%) CIN III, and 18 of 21 (86%) cervical cancer lesions were telomerase-positive (P &lt; .0005). Telomerase activity levels in paired scrapings and frozen sections appeared to be only weakly related; telomerase-positive sections with negative scrapings and vice versa (only in CIN III) were observed. In oncogenic HPV-negative scrapings (n = 14), no telomerase activity was detected, but in frozen sections, telomerase activity levels appeared to be unrelated to presence of specific HPV types. CONCLUSION Telomerase activity is more frequent in higher grade CIN/cervical cancer lesions. Telomerase activity assessment in cervical scrapings has a low sensitivity for CIN II/III and/or cervical cancer and does not appear to be useful in primary screening for cervical cancer. However, increased telomerase activity in frozen CIN sections may be a possible marker of progressive disease.
Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism
Authors: Benjamin G. Chousterman, Alexandre Boissonnas, Lucie Poupel, Camille Baudesson de Chanville, Julien Adam, Nahid Tabibzadeh, Fabrice Licata, Anne-Claire Lukaszewicz, Amélie Lombès, Philippe Deterre, Didier Payen, Christophe Combadière
Journal: Journal of the American Society of Nephrology (2015)

Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.
Clinical Usefulness of Microarrays for Cancer Prognosis in 2010—Letter
Authors: Serge Koscielny, Stefan Michiels
Journal: Clinical Cancer Research (2010)

We read with interest the recent article by Fan et al. (1) reanalyzing our review (2) published 5 years ago. Many players in the bioinformatics field criticized our study because we used a prediction rule considered too “simple.” We are glad to see that the use of more complex rules only minimally affected the prediction accuracy.The main objective of our study was to put a nail in the coffin of the custom application of inadequate validation procedures, which consisted in playing with the analytical mode on a training–test pair of data sets until the result was considered good enough for publication. We are not convinced that this plague has been eradicated in 2010. In our view, a priori specification of the methods used to divide the data and determine the gene signature, that is, the selection of the genes, prediction rule, and cutoffs (3), was and is a valid approach for hypothesis-driven research and, in this case, leads to the generalizability of prediction accuracy estimates for future patients. In contrast, trying several alternative methods and choosing the most optimal among them was and still is a good way to generate false-positive results or to support unduly optimistic views.One major conclusion of the new reanalysis is that 6 of 7 data sets yielded a prediction accuracy in the training set that was better than chance. Of note, the data set with the strongest signal compared with a null data set (as measured by Cohen's d statistic, Fig. 4) was the breast cancer data set, which was actually the one for which we also found the highest prediction accuracy and the only one that passed our multiple random validation strategy with flying colors (2). Today, that is 5 years later, it is the only one from the 7 studies that has stood the test of time in 2 subsequent independent validation studies (4).Many classifiers have been reported to perform better than chance; very few are validated in truly independent validations studies. The important questions in 2010 concern their place in clinical practice compared with widely established clinical prediction methods: for example, what does the gene signature in breast cancer add to the best clinical model, based on nodal status, age, tumor stage and grade, for predicting the occurrence of distant metastases (3)? Actually, what is the clinical usefulness of any of the published gene signatures (including those that have a prediction accuracy slightly better than that expected by chance; ref. 5)?See the Response, p. 6181No potential conflicts of interest were disclosed.
P171 Efficacy and safety of bronchial thermoplasty in clinical practice: early results from a national registry: Abstract P171 Table 1.
Authors: J Burn, Aj Sims, Dr Bousfield, H Patrick, S Welham, Lg Heaney
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> NICE Guidance for bronchial thermoplasty (BT) recommended the collection of safety and efficacy outcomes through the BTS Difficult Asthma Registry. This study summarises the data collected to June 2013, with objectives of describing the demographic and baseline characteristics of patients undergoing BT and early consideration of safety and efficacy, which will be updated for presentation at the December 2013 meeting. <h3>Methods</h3> Records for 21 patients from 5 UK centres were studied. Age, gender, lung function and quality of life were compared to those reported in two previous clinical trials. Potential safety issues were examined and efficacy outcomes compared to baseline. <h3>Results</h3> Data:20 baseline records, 62 BT procedure records, 9 patients followed up to 6 months, 7 followed up to 12 months. At follow-up, 12 patients had data at 6 and/or 12 months for pre bronchodilator FEV<sub>1</sub> and AQLQ to enable comparison with baseline. Baseline demographics and characteristics are presented in Table 1. Outcomes: one patient was re-admitted to hospital for 3 days with an exacerbation after the second of three routine BT procedures, but recovered to complete the final procedure. 17 patients were admitted post-procedure (max 8 days) but no adverse outcomes were reported. Mean AQLQ score at 6 months was 4.61 ± 1.80 (n = 10). 6/10 patients had improved AQLQ (&gt; 0.5 above baseline) at 6 months and 2/3 at 12 months. 1/10 patients had worse AQLQ (&gt; than 0.5 below baseline) at 6 months and 0/3 at 12 months. Mean pre-bronchodilator FEV<sub>1</sub> (% of predicted) at 6 months was 64.88 ± 26.57 (n = 8) and at 12 months 75.20 ± 13.77 (n = 5). <h3>Conclusions</h3> Early indications are that this cohort are marginally older and have worse mean lung function and AQLQ scores at baseline than patients in two previous clinical trials.No serious issues relating to equipment or adverse outcomes were observed. Patients were often admitted post-procedure - this may have been precautionary, as there were no reports of unanticipated procedural morbidity. To date, efficacy outcomes appear consistent with those observed in previous clinical trials, with a suggestion of smaller improvement in AQLQ score.
Reprogramming of the Macrophage Transcriptome in Response to Interferon-γ and <i>Mycobacterium tuberculosis</i>
Authors: Sabine Ehrt, Dirk Schnappinger, Stefan Bekiranov, Jörg Drenkow, Shuangping Shi, Thomas R. Gingeras, Terry Gaasterland, Gary Schoolnik, Carl Nathan
Journal: The Journal of Experimental Medicine (2001)

Macrophage activation determines the outcome of infection by Mycobacterium tuberculosis (Mtb). Interferon-γ (IFN-γ) activates macrophages by driving Janus tyrosine kinase (JAK)/signal transducer and activator of transcription–dependent induction of transcription and PKR-dependent suppression of translation. Microarray-based experiments reported here enlarge this picture. Exposure to IFN-γ and/or Mtb led to altered expression of 25% of the monitored genome in macrophages. The number of genes suppressed by IFN-γ exceeded the number of genes induced, and much of the suppression was transcriptional. Five times as many genes related to immunity and inflammation were induced than suppressed. Mtb mimicked or synergized with IFN-γ more than antagonized its actions. Phagocytosis of nonviable Mtb or polystyrene beads affected many genes, but the transcriptional signature of macrophages infected with viable Mtb was distinct. Studies involving macrophages deficient in inducible nitric oxide synthase and/or phagocyte oxidase revealed that these two antimicrobial enzymes help orchestrate the profound transcriptional remodeling that underlies macrophage activation.
The Neuropharmacokinetics of Temozolomide in Patients with Resectable Brain Tumors: Potential Implications for the Current Approach to Chemoradiation
Authors: Jana Portnow, Behnam Badie, Mike Chen, An Liu, Suzette Blanchard, Timothy W. Synold
Journal: Clinical Cancer Research (2009)

Purpose: Intracerebral microdialysis (ICMD) is an accepted method for monitoring changes in neurochemistry from acute brain injury. The goal of this pilot study was to determine the feasibility of using ICMD to examine the neuropharmacokinetics of temozolomide in brain interstitium following oral administration.Experimental Design: Patients with primary or metastatic brain tumors had a microdialysis catheter placed in peritumoral brain tissue at the time of surgical debulking. Computerized tomography scan confirmed the catheter location. Patients received a single oral dose of temozolomide (150 mg/m2) on the first postoperative day, serial plasma and ICMD samples were collected over 24 hours, and temozolomide concentrations were determined by tandem mass spectrometry.Results: Nine patients were enrolled. Dialysate and plasma samples were successfully collected from seven of the nine patients. The mean temozolomide areas under the concentration-time curve (AUC) in plasma and brain interstitium were 17.1 and 2.7 g/mL hour, with an average brain interstitium/plasma AUC ratio of 17.8. The mean peak temozolomide concentration in the brain was 0.6 0.3 g/mL, and the mean time to reach peak level in brain was 2.0 0.8 hours.Conclusions: The use of ICMD to measure the neuropharmacokinetics of systemically administered chemotherapy is safe and feasible. Concentrations of temozolomide in brain interstitium obtained by ICMD are consistent with published data obtained in a preclinical ICMD model, as well as from clinical studies of cerebrospinal fluid. However, the delayed time required to achieve maximum temozolomide concentrations in brain suggests that current chemoradiation regimens may be improved by administering temozolomide 2 to 3 hours before radiation. (Clin Cancer Res 2009;15(22):70928)
Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach
Authors: P. L. P. Brand, E. Baraldi, H. Bisgaard, A. L. Boner, J. A. Castro-Rodriguez, A. Custovic, J. de Blic, J. C. de Jongste, E. Eber, M. L. Everard, U. Frey, M. Gappa, L. Garcia-Marcos, J. Grigg, W. Lenney, P. Le Souëf, S. McKenzie, P. J. F. M. Merkus, F. Midulla, J. Y. Paton, G. Piacentini, P. Pohunek, G. A. Rossi, P. Seddon, M. Silverman, P. D. Sly, S. Stick, A. Valiulis, W. M. C. van Aalderen, J. H. Wildhaber, G. Wennergren, N. Wilson, Z. Zivkovic, A. Bush
Journal: European Respiratory Journal (2008)

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting β 2 -agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.