tbuckley/cabot-search huggingface dataset:
Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology
Authors: A. K. Gnekow, F. Falkenstein, S. von Hornstein, I. Zwiener, S. Berkefeld, B. Bison, M. Warmuth-Metz, P. H. Driever, N. Soerensen, R.-D. Kortmann, T. Pietsch, A. Faldum
Journal: Neuro-Oncology (2012)

The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment.
Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.
Authors: H K Seitz, G Egerer, U A Simanowski, R Waldherr, R Eckey, D P Agarwal, H W Goedde, J P von Wartburg
Journal: Gut (1993)

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p &lt; 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p &lt; 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people.
Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear
Authors: Jeremy L. Pinyon, Sherif F. Tadros, Kristina E. Froud, Ann C. Y. Wong, Isabella T. Tompson, Edward N. Crawford, Myungseo Ko, Renée Morris, Matthias Klugmann, Gary D. Housley
Journal: Science Translational Medicine (2014)

Neurotrophin gene delivery, achieved by “close-field” electroporation of mesenchymal cells adjacent to the cochlear implant, improved hearing in deafened guinea pigs.
Efficiency of cold passover and heated humidification under continuous positive airway pressure
Authors: W.J. Randerath, J. Meier, H. Genger, U. Domanski, K‐H. Rühle
Journal: European Respiratory Journal (2002)

Cold passover and heated humidifiers are employed for the prevention of side-effects associated with continuous positive airway pressure (CPAP) treatment. However, to date, it has not been possible to separately measure the humidity of inspired and expired air. The aim of this study was to compare the relative humidity of the inspired air and the water loss during respiration between cold passover and heated humidifiers under CPAP. Humidity and temperature were determined separately for the respiratory phases, without humidification, with cold passover and heated humidifiers in 10 healthy subjects. Humidity was measured with a capacitive hygrometer, temperature with a “Type K” thermosensor, and impedance of the total respiratory system with impulse oscillometry. The relative humidity (rH) of the inspired air (mean±sd) increased significantly from 24.0±9.1% rH (34.8±1.0°C, no humidifier) to 34.5±10.1% rH (34.6±1.0°C) under cold humidification, and to 53.9±13.2% rH (35.0±1.1°C) under heated humidification. With heated humidification, water loss was reduced by 38% compared to cold humidification. The impedance increased from 5.7±1.8 cmH 2 O·L·s −1 (no humidifier) to 6.7±1.8 cmH 2 O·L·s −1 (heated humidifier). The authors conclude that the use of a heated humidifier during continuous positive airway pressure appreciably increases the relative humidity of the inspired air and reduces the water loss during respiration.
MRI observations at return to play of clinically recovered hamstring injuries
Authors: Gustaaf Reurink, Gert Jan Goudswaard, Johannes L Tol, Emad Almusa, Maarten H Moen, Adam Weir, Jan A N Verhaar, Bruce Hamilton, Mario Maas
Journal: British Journal of Sports Medicine (2013)

Background Previous studies have shown that MRI of fresh hamstring injuries have diagnostic and prognostic value. The clinical relevance of MRI at return to play (RTP) has not been clarified yet. The aim of this study is to describe MRI findings of clinically recovered hamstring injuries in amateur, elite and professional athletes that were cleared for RTP. Methods We obtained MRI of 53 consecutive athletes with hamstring injuries within 5 days of injury and within 3 days of RTP. We assessed the following parameters: injured muscle, grading of injury, presence and extent of intramuscular signal abnormality. We recorded reinjuries within 2 months of RTP. Results MRIs of the initial injury showed 27 (51%) grade 1 and 26 (49%) grade 2 injuries. Median time to RTP was 28 days (range 12–76). On MRI at RTP 47 athletes (89%) had intramuscular increased signal intensity on fluid-sensitive sequences with a mean longitudinal length of 77 mm (±53) and a median cross-sectional area of 8% (range 0–90%) of the total muscle area. In 22 athletes (42%) there was abnormal intramuscular low-signal intensity. We recorded five reinjuries. Conclusions 89% of the clinically recovered hamstring injuries showed intramuscular increased signal intensity on fluid-sensitive sequences on MRI. Normalisation of this increased signal intensity seems not required for a successful RTP. Low-signal intensity suggestive of newly developed fibrous tissues is observed in one-third of the clinically recovered hamstring injuries on MRI at RTP, but its clinical relevance and possible association with increased reinjury risk has to be determined.
Impaired degranulation but enhanced cytokine production after FcεRI stimulation of diacylglycerol kinase ζ–deficient mast cells
Authors: Benjamin A. Olenchock, Rishu Guo, Michael A. Silverman, Jennifer N. Wu, Jeffery H. Carpenter, Gary A. Koretzky, Xiao-Ping Zhong
Journal: The Journal of Experimental Medicine (2006)

Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound FcεRI. Diacylglycerol kinase (DGK)ζ is a negative regulator of diacylglycerol-dependent signaling that acts by converting diacylglycerol to phosphatidic acid. We reported previously that DGKζ−/− mice have enhanced in vivo T cell function. Here, we demonstrate that these mice have diminished in vivo mast cell function, as revealed by impaired local anaphylactic responses. Concordantly, DGKζ−/− bone marrow–derived mast cells (BMMCs) demonstrate impaired degranulation after FcεRI cross-linking, associated with diminished phospholipase Cγ activity, calcium flux, and protein kinase C–βII membrane recruitment. In contrast, Ras-Erk signals and interleukin-6 production are enhanced, both during IgE sensitization and after antigen cross-linking of FcεRI. Our data demonstrate dissociation between cytokine production and degranulation in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenuation of FcεRI signals.
Recent Insights into the Cell Biology of Thyroid Angiofollicular Units
Authors: Ides M. Colin, Jean-François Denef, Benoit Lengelé, Marie-Christine Many, Anne-Catherine Gérard
Journal: Endocrine Reviews (2013)

In thyrocytes, cell polarity is of crucial importance for proper thyroid function. Many intrinsic mechanisms of self-regulation control how the key players involved in thyroid hormone (TH) biosynthesis interact in apical microvilli, so that hazardous biochemical processes may occur without detriment to the cell. In some pathological conditions, this enzymatic complex is disrupted, with some components abnormally activated into the cytoplasm, which can lead to further morphological and functional breakdown. When iodine intake is altered, autoregulatory mechanisms outside the thyrocytes are activated. They involve adjacent capillaries that, together with thyrocytes, form the angiofollicular units (AFUs) that can be considered as the functional and morphological units of the thyroid. In response to iodine shortage, a rapid expansion of the microvasculature occurs, which, in addition to nutrients and oxygen, optimizes iodide supply. These changes are triggered by angiogenic signals released from thyrocytes via a reactive oxygen species/hypoxia-inducible factor/vascular endothelial growth factor pathway. When intra- and extrathyrocyte autoregulation fails, other forms of adaptation arise, such as euthyroid goiters. From onset, goiters are morphologically and functionally heterogeneous due to the polyclonal nature of the cells, with nodules distributed around areas of quiescent AFUs containing globules of compact thyroglobulin (Tg) and surrounded by a hypotrophic microvasculature. Upon TSH stimulation, quiescent AFUs are activated with Tg globules undergoing fragmentation into soluble Tg, proteins involved in TH biosynthesis being expressed and the local microvascular network extending. Over time and depending on physiological needs, AFUs may undergo repetitive phases of high, moderate, or low cell and tissue activity, which may ultimately culminate in multinodular goiters.
Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal MRI Study
Authors: Nancy C. Andreasen, Dawei Liu, Steven Ziebell, Anvi Vora, Beng-Choon Ho
Journal: American Journal of Psychiatry (2013)

Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question.The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years.Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity.Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.
Prospective Study of [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography and Magnetic Resonance Imaging in Oral Cavity Squamous Cell Carcinoma With Palpably Negative Neck
Authors: Shu-Hang Ng, Tzu-Chen Yen, Joseph Tung-Chieh Chang, Sheng-Chieh Chan, Sheung-Fat Ko, Hung-Ming Wang, Li-Yu Lee, Chung-Jan Kang, Alex Mun-Ching Wong, Chun-Ta Liao
Journal: Journal of Clinical Oncology (2006)

Purpose To assess the clinical usefulness of [ 18 F]fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET) as well as computed tomography (CT) or magnetic resonance imaging (MRI) in oral squamous cell carcinoma (SCC) patients with palpably negative neck. Patients and Methods In total, 134 oral SCC patients with palpably negative neck were prospectively evaluated with [ 18 F]FDG PET, CT/MRI, and their visual correlation. Histopathologic analysis was used as the gold standard for assessment of these imaging techniques. Results Thirty-five (26.1%) of our 134 patients were found to have neck metastases. On a level-by-level basis, the sensitivity of [ 18 F]FDG PET for nodal metastases was two-fold higher than that of CT/MRI (41.2% v 21.6%, respectively; P = .021). Visual correlation of [ 18 F]FDG PET and CT/MRI yielded slightly higher sensitivity and specificity than [ 18 F]FDG PET alone (47.1% v 41.2%, P = .25; 98.0% v 96.8%, P = .125, respectively). On a patient-by-patient basis, the sensitivity of [ 18 F]FDG PET for neck metastases was 51.4% and increased to 57.1% after visual correlation with CT/MRI. The probabilities of occult neck metastasis after using [ 18 F]FDG PET were 6.7% in T1 tumors, 10.8% in T2 tumors, 13.3% in T3 tumors, and 25% in T4 tumors and decreased to 3.3% in T1 tumors and to 9.2% in T2 tumors after visual correlation with CT/MRI. Conclusion [ 18 F]FDG PET was superior to CT/MRI for detecting palpably occult neck metastasis of oral SCC. Because [ 18 F]FDG PET could reduce the probability of occult neck metastasis to less than 15% in T1 to T3 tumors, it should be indicated for evaluation of these subpopulations.
Evaluation of the effect of diagnostic methodology on the reported incidence of ventilator-associated pneumonia
Authors: A C. Morris, K Kefala, A J Simpson, T S Wilkinson, K Everingham, D Kerslake, S Raby, I F Laurenson, D G Swann, T S Walsh
Journal: Thorax (2009)

<h3>Background:</h3> The optimal method for diagnosing ventilator-associated pneumonia (VAP) is controversial and its effect on reported incidence uncertain. This study aimed to model the impact of using either endotracheal aspirate or bronchoalveolar lavage on the reported incidence of pneumonia and then to test effects suggested from theoretical modelling in clinical practice. <h3>Methods:</h3> A three-part single-centre study was undertaken. First, diagnostic performance of aspirate and lavage were compared using paired samples from 53 patients with suspected VAP. Secondly, infection surveillance data were used to model the potential effect on pneumonia incidence and antibiotic use of using exclusively aspirate or lavage to investigate suspected pneumonia (643 patients; 110 clinically suspected pneumonia episodes). Thirdly, a practice change initiative was undertaken to increase lavage use; pneumonia incidence and antibiotic use were compared for the 12 months before and after the change. <h3>Results:</h3> Aspirate overdiagnosed VAP compared with lavage (89% vs 21% of clinically suspected cases, p&lt;0.0001). Modelling suggested that changing from exclusive aspirate to lavage diagnosis would decrease reported pneumonia incidence by 76% (95% CI 67% to 87%) and antibiotic use by 30% (95% CI 20% to 42%). After the practice change initiative, lavage use increased from 37% to 58%. Although clinically suspected pneumonia incidence was unchanged, microbiologically confirmed VAP decreased from 18 to 9 cases per 1000 ventilator days (p = 0.001; relative risk reduction 0.61 (95% CI 0.46 to 0.82)), and mean antibiotic use fell from 9.1 to 7.2 antibiotic days (21% decrease, p = 0.08). <h3>Conclusions:</h3> Diagnostic technique impacts significantly on reported VAP incidence and potentially on antibiotic use.
Similar response rates in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis after 1 year of treatment with etanercept: results from the ESTHER trial
Authors: In-Ho Song, Anja Weiß, Kay-Geert A Hermann, Hildrun Haibel, Christian E Althoff, Denis Poddubnyy, Joachim Listing, Ekkehard Lange, Bruce Freundlich, Martin Rudwaleit, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2012)

Objective We assessed whether there is a difference to etanercept (ETA) treatment in patients with ankylosing spondylitis (AS) compared with non-radiographic axial SpA (nr-axSpA) patients with a disease duration &lt;5 years. Method AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1 year were compared for differences in baseline data and treatment effect. Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were analysed. Results At baseline, there were no significant differences between the 20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA-B27 and clinical disease activity in terms of Bath AS Disease Activity Index (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to 3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8 (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively. Conclusions The response rate to TNF-blockers does not differ between AS and nr-axSpA if the baseline data regarding symptom duration and disease activity are similar for the two groups.
Increased cytotoxicity of normal rabbit serum for lectin-resistant mutants of animal cells.
Authors: C Jones
Journal: The Journal of Experimental Medicine (1984)

Plant lectins are cytotoxic and can be used to select for mutants of animal cells that exhibit structural changes in cell surface carbohydrates reflecting glycosylation defects. We isolated eight lectin mutants of Chinese hamster ovary (CHO) cells that appear to represent three different phenotype classes. These lectin mutants were much more sensitive to the cytotoxic action of normal rabbit serum (NRS) than were the parental cells. This increased cytotoxicity was heat sensitive, specifically absorbed, and inhibited by simple and complex carbohydrates. No killing was observed under conditions in which only the alternate complement pathway was active. An NRS-resistant subclone that was isolated from one lectin mutant was shown to have also regained wild type behavior when tested with the lectins. The possibility that naturally occurring antibodies in rabbit serum are reacting with incomplete carbohydrate chains on the surface of the lectin mutants is discussed.
Mechanisms of Action of and Resistance to Antitubulin Agents: Microtubule Dynamics, Drug Transport, and Cell Death
Authors: Charles Dumontet, Branimir I. Sikic
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To analyze the available data concerning mechanisms of action of and mechanisms of resistance to the antitubulin agents, vinca alkaloids and taxanes, and more recently described compounds. DESIGN: We conducted a review of the literature on classic and recent antitubulin agents, focusing particularly on the relationships between antitubulin agents and their intracellular target, the soluble tubulin/microtubule complex. RESULTS AND CONCLUSION: Although it is widely accepted that antitubulin agents block cell division by inhibition of the mitotic spindle, the mechanism of action of antitubulin agents on microtubules remains to be determined. The classic approach is that vinca alkaloids depolymerize microtubules, thereby increasing the soluble tubulin pool, whereas taxanes stabilize microtubules and increase the microtubular mass. More recent data suggest that both classes of agents have a similar mechanism of action, involving the inhibition of microtubule dynamics. These data suggest that vinca alkaloids and taxanes may act synergistically as antitumor agents and may be administered as combination chemotherapy in the clinic. However, enhanced myeloid and neurologic toxicity, as well as a strong dependence on the sequence of administration, presently exclude these combinations outside the context of clinical trials. Although the multidrug resistance phenotype mediated by Pgp appears to be an important mechanism of resistance to these agents, alterations of microtubule structure resulting in altered microtubule dynamics and/or altered binding of antitubulin agents may constitute a significant mechanism of drug resistance.