tbuckley/cabot-search huggingface dataset:
Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy
Authors: D. Ennishi, H. Asai, Y. Maeda, K. Shinagawa, K. Ikeda, M. Yokoyama, Y. Terui, K. Takeuchi, T. Yoshino, K. Matsuo, K. Hatake, M. Tanimoto
Journal: Annals of Oncology (2009)
Structural and Functional Characterization of Csda Protein Complexes Involved In Modulation of Fetal Globin Gene Expression
Authors: Sara Gaudino, Raffaella Petruzzelli, Giovanni Amendola, Raffaele Sessa, Stella Puzone, Antonio M. Risitano, Maria Rosaria Storino, Rosanna Di Concilio, Giovanna D’Urzo, Maria Amendolara, Annamaria Aurino, Paola Izzo, Michela Grosso
Journal: Blood (2010)
Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts
Authors: Miriam E. Mossoba, Masanori Onda, Justin Taylor, Paul R. Massey, Shirin Treadwell, Elad Sharon, Raffit Hassan, Ira Pastan, Daniel H. Fowler
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity. Experimental Design: BALB/c hosts were injected weekly with recombinant immunotoxin (RIT) SS1P, which is an antimesothelin Fv antibody fragment genetically fused to a 38 kDa portion of PE, and has been evaluated in clinical trials. Experimental cohorts received induction chemotherapy consisting of pentostatin (P) plus cyclophosphamide (C) prior to initial RIT exposure; some cohorts received further maintenance PC therapy of varying intensity just prior to each weekly RIT challenge. Cohorts were monitored for T, B, myeloid cell depletion, and for total anti-SS1P antibody (Ab) formation. Results: Controls uniformly developed anti-SS1P Ab after the third RIT exposure. Induction PC therapy reduced the frequency of hosts with anti-SS1P Ab. Abrogation of antibody generation was improved by maintenance PC therapy: nearly 100% of recipients of intensive PC maintenance were free of anti-SS1P Ab after 9 weekly RIT doses. The most effective PC regimen yielded the greatest degree of host B-cell depletion, moderate T-cell depletion, and minimal myeloid cell depletion. Conclusions: Induction and maintenance PC chemotherapy safely prevented anti-immunotoxin antibody formation with uniform efficacy. These data suggest that immunotoxin therapy might be used in combination with pentostatin plus cyclophosphamide chemotherapy to improve the targeted therapy of cancer. Clin Cancer Res; 17(11); 3697–705. ©2011 AACR.
Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine.
Authors: C S Potten, M Kellett, S A Roberts, D A Rew, G D Wilson
Journal: Gut (1992)

In vivo bromodeoxyuridine (BrdUrd) labelling of the human large bowel was performed and a detailed histochemical localisation of label in sections of crypts was undertaken using a monoclonal antibody to BrdUrd containing DNA. Flow cytometric studies on extracted nuclei were also performed (data presented elsewhere). The average crypt in the human large bowel (excluding the rectum) was 82 cells in height and 41 cells in circumference, with a total of about 2000 cells (assuming a topographical correction factor of 0.6). Ten per cent of the cells were replicating their DNA--that is, were in the S phase of the cell cycle--and 0.4% were in mitosis. The median position for the labelling index versus cell position frequency plot is at the 20th cell position--at a quarter of the crypt height. The lower and upper limits of the cell proliferation are given by the 5th and 95th percentiles at cell positions 4 and 43 respectively. The peak labelling index is about 30% and it occurs at cell position 15. The labelling index at the crypt base, the probable stem cell zone, is about 14%, suggesting that these cells have a longer cell cycle. Taking a value of 8.6 hours for the duration of the S phase (deduced from the flow cytometric data) and assuming a growth fraction of 1.0 for the mid-crypt, these data provide an estimate of about 30 hours for the cell cycle time. The rectal crypts are about the same size but contain about 30% fewer S phase cells. The data also yielded a per cent BrdUrd labelled mitosis curve.
THE ABSORPTION OF ADRENALIN
Authors: D. Murray Lyon
Journal: The Journal of Experimental Medicine (1923)

1. Adrenalin solution given subcutaneously is usually rapidly absorbed, probably by lymphatic channels. 2. The speed of this process may be influenced by the circulation rate. 3. The relative amounts of adrenalin at any moment unabsorbed at the site of inoculation, carried in the circulating fluids, and taken up by the reacting tissues can be calculated from figures extracted from the curve of the blood pressure changes. The relative rates of transference of adrenalin into the blood and from the circulation into the tissues can also be estimated. 4. When absorption takes place rapidly a large quantity of the drug comes into action at once and the maximum occurs early, the curve of blood pressure reaches a considerable height, and subsides quickly. When absorption is slow the apex appears later and does not reach so high a level. 5. The response to adrenalin bears a logarithmic relationship to the dose employed and a method of allowing for this is indicated.
Biosynthesis and release of thyrotropin-releasing hormone immunoreactivity in rat pancreatic islets in organ culture. Effects of age, glucose, and streptozotocin.
Authors: L O Dolva, J H Nielsen, B S Welinder, K F Hanssen
Journal: Journal of Clinical Investigation (1983)

Thyrotropin-releasing hormone immunoreactivity (TRH-IR) was measured in isolated islets and in medium from rat pancreatic islets maintained in organ culture. TRH-IR in methanol extracts of both islets and culture medium was eluted in the same position as synthetic TRH by ion-exchange and gel chromatography and exhibited dilution curves parallel with synthetic TRH in radioimmunoassay. [3H]Histidine was incorporated into a component that reacted with TRH antiserum and had the same retention time as synthetic TRH on reversed-phase high-performance liquid chromatography. A continuous release of TRH-IR into the culture medium was observed from islets of both 5-d-old (newborn) and 30-d-old (adult) rats with a maximum on the second day of culture (28.7 +/- 7.0 and 13.3 +/- 3.6 fmol/islet per d, respectively). The content of TRH-IR was higher in freshly isolated islets from newborn rats (22.4 +/- 2.3 fmol/islet) than in adult rat islets, which, however, increased their content from 1.3 +/- 0.5 to 7.0 +/- 0.5 fmol/islet during the first 3 d of culture. Adult rat islets maintained in medium with 20 mM glucose released significantly more TRH-IR than islets in 3.3 mM glucose medium (13.0 +/- 0.7 vs. 4.3 +/- 0.3 fmol/islet per d). In contrast, the content of TRH-IR in the islets was reversed (1.4 +/- 0.3 vs. 4.7 +/- 1.6 fmol/islet). By exposing islets from newborn rats to streptozotocin 0.7 mg/ml for 30 min, a 50% reduction of TRH-IR content in the islets compared with the non-treated islets was seen after subsequent culture for 7 d. The insulin content was reduced by 80%, while glucagon was slightly elevated. In conclusion, these results indicate that TRH is synthesized in rat pancreatic islets, and that the release is stimulated by glucose.
Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis
Authors: H Mukae
Journal: Thorax (2002)

<b>Background:</b> Neutrophils are thought to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Human neutrophils contain antimicrobial and cytotoxic peptides in the azurophil granules which belong to a family of mammalian neutrophil peptides named α-defensins. A study was undertaken to investigate the role of α-defensins in the pathogenesis of IPF. <b>Methods:</b> The concentrations of α-defensins (human neutrophil peptides (HNPs) 1, 2, and 3) in plasma and bronchoalveolar lavage (BAL) fluid of 30 patients with IPF and 15 healthy subjects were measured by radioimmunoassay. <b>Results:</b> The concentrations of α-defensins in plasma, but not in BAL fluid, were significantly higher in IPF patients than in controls. BAL fluid concentrations of interleukin (IL)-8 in patients with IPF, which were significantly higher than in controls, correlated with those of α-defensins. An inverse relationship was seen between plasma α-defensin levels and the arterial oxygen tension (Pao<sub>2</sub>) and pulmonary function (vital capacity (%VC), forced expiratory volume in 1 second (FEV<sub>1</sub>), and carbon monoxide transfer factor (%Tlco)) in patients with IPF. Plasma levels of α-defensins also correlated with the clinical course in IPF patients with an acute exacerbation. Immunohistochemically, positive staining was observed inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas. <b>Conclusion:</b> These findings suggest that α-defensins play an important role in the pathogenesis of IPF, and that the plasma α-defensin level may be a useful marker of disease severity and activity.
Novel Aspects of Dietary Nitrate and Human Health
Authors: Eddie Weitzberg, Jon O. Lundberg
Journal: Annual Review of Nutrition (2013)

The circulation of nitrogen in nature is a prerequisite for life on earth. In the nitrogen cycle atmospheric nitrogen is fixated by bacteria into forms that can be utilized by plants and mammals. Nitrate and nitrite are obligate intermediates in this cycle, and for more than half a century these anions have interested nutritional scientists, mostly in relation to cancer, because of their ability to form nitrosamines. However, after the discovery of mammalian endogenous nitric oxide (NO) generation and later that its oxidation products nitrate and nitrite can be recycled back to bioactive NO, a novel field of research has emerged that explores a potentially beneficial role of these anions in physiology, nutrition, and therapeutics. In our diet, vegetables are the major source of nitrate that can fuel a nitrate-nitrite-NO pathway. Herein we discuss the nutritional aspects of this pathway and what is presently known about the implications for human health.
Deletion of <i>Pten</i> Expands Lung Epithelial Progenitor Pools and Confers Resistance to Airway Injury
Authors: Caterina Tiozzo, Stijn De Langhe, Mingke Yu, Vedang A. Londhe, Gianni Carraro, Min Li, Changgong Li, Yiming Xing, Stewart Anderson, Zea Borok, Saverio Bellusci, Parviz Minoo
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Pten is a tumor-suppressor gene involved in stem cell homeostasis and tumorigenesis. In mouse, Pten expression is ubiquitous and begins as early as 7 days of gestation. Pten(-/-) mouse embryos die early during gestation indicating a critical role for Pten in embryonic development.To test the role of Pten in lung development and injury.We conditionally deleted Pten throughout the lung epithelium by crossing Pten(flox/flox) with Nkx2.1-cre driver mice. The resulting Pten(Nkx2.1-cre) mutants were analyzed for lung defects and response to injury.Pten(Nkx2.1-cre) embryonic lungs showed airway epithelial hyperplasia with no branching abnormalities. In adult mice, Pten(Nkx2.1-cre) lungs exhibit increased progenitor cell pools composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar duct junctions. Pten deletion affected differentiation of various lung epithelial cell lineages, with a decreased number of terminally differentiated cells. Over time, Pten(Nxk2.1-cre) epithelial cells residing in the bronchioalveolar duct junctions underwent proliferation and formed uniform masses, supporting the concept that the cells residing in this distal niche may also be the source of procarcinogenic stem cells. Finally, increased progenitor cells in all the lung compartments conferred an overall selective advantage to naphthalene injury compared with wild-type control mice.Pten has a pivotal role in lung stem cell homeostasis, cell differentiation, and consequently resistance to lung injury.
The endogenous mink cell focus-forming (MCF) gp70 linked to the Rmcf gene restricts MCF virus replication in vivo and provides partial resistance to erythroleukemia induced by Friend murine leukemia virus.
Authors: R S Buller, M Sitbon, J L Portis
Journal: The Journal of Experimental Medicine (1988)

The Rmcf locus restricts the in vitro replication of mink cell focus-forming (MCF) viruses in cell cultures derived from mice carrying the resistance allele. Previously we reported that in cell cultures from first backcross progeny, this Rmcf-linked restriction segregates with the expression of an endogenous retroviral gp70 serologically related to that of MCF viruses. The current report details the results of genetic studies designed to examine the possible association of this endogenous gp70 with resistance of mice to Friend murine leukemia virus (F-MuLV)-induced erythroleukemia. This env gene segregates as a single dominant trait in (DBA/2 X IRW) X IRW progeny, in which the expression of the gene can be detected by serological techniques. Results indicated that the gp70- progeny developed leukemia at the same rate as the susceptible IRW parent, whereas the tempo of disease among the gp70+ progeny was significantly slower. However, the resistance mediated by this gene was only partial, since most of the gp70+ offspring eventually developed erythroleukemia when followed for 6 mo. This endogenous gp70 also segregated with a restriction to the expression of recombinant MCF viruses after infection with F-MuLV. Since in this study all unlinked genes segregated independently, this is direct evidence that MCF viruses participate in the induction of erythroleukemia.
A link between FTO, ghrelin, and impaired brain food-cue responsivity
Authors: Efthimia Karra, Owen G. O’Daly, Agharul I. Choudhury, Ahmed Yousseif, Steven Millership, Marianne T. Neary, William R. Scott, Keval Chandarana, Sean Manning, Martin E. Hess, Hiroshi Iwakura, Takashi Akamizu, Queensta Millet, Cigdem Gelegen, Megan E. Drew, Sofia Rahman, Julian J. Emmanuel, Steven C.R. Williams, Ulrich U. Rüther, Jens C. Brüning, Dominic J. Withers, Fernando O. Zelaya, Rachel L. Batterham
Journal: Journal of Clinical Investigation (2013)

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.
START lipid/sterol-binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors
Authors: Kathrin Schrick, Diana Nguyen, Wojciech M Karlowski, Klaus FX Mayer
Journal: Genome biology (2004)

In animals, steroid hormones regulate gene expression by binding to nuclear receptors. Plants lack genes for nuclear receptors, yet genetic evidence from Arabidopsis suggests developmental roles for lipids/sterols analogous to those in animals. In contrast to nuclear receptors, the lipid/sterol-binding StAR-related lipid transfer (START) protein domains are conserved, making them candidates for involvement in both animal and plant lipid/sterol signal transduction.
A STUDY OF RENAL FUNCTION IN ROENTGEN RAY INTOXICATION
Authors: Irvine McQuarrie, G. H. Whipple
Journal: The Journal of Experimental Medicine (1922)

Our experiments give no support to the current belief that an x-ray nephritis may be produced by direct or indirect action of the hard Roentgen rays. Moderate doses of x-rays given repeatedly over considerable periods of time have no demonstrable influence on renal function or renal structure. With x-ray exposures of the abdomen and shielding of the kidneys fatal intoxication may be produced without the slightest disturbance of kidney function as measured by the ability of the kidney to eliminate phenolphthalein and urea. Large doses of the x-rays given directly over the kidney may cause a slight but distinct lowering of renal function which lasts for a period of a few days. We have been unable to recognize any corresponding histological change. We feel that the usual therapeutic doses of the x-rays can be given over the kidneys without apprehension. The renal tissue is much more resistant to x-rays than is the epithelium of the small intestine.
Hemiballism-hemichorea induced by ketotic hyperglycemia: case report with PET study and review of the literature
Authors: Yuyan Tan, Xiaoyu Xin, Qin Xiao, Shengdi Chen, Li Cao, Huidong Tang
Journal: Translational Neurodegeneration (2014)

Hemiballism-hemichorea (HB-HC) is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients. Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones. We described the computed tomography and magnetic resonance imaging findings in these two patients, which is similar to that of non-ketotic hyperglycemic HB-HC patients. FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other. We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages.
Glutathione S-transferase, incense burning and asthma in children
Authors: I-J. Wang, C-H. Tsai, C-H. Chen, K-Y. Tung, Y.L. Lee
Journal: European Respiratory Journal (2010)

Incense burning is a popular practice in many family homes and temples. However, little is known about the effects of indoor incense burning and genetic polymorphisms on asthma. This study evaluated the effects of indoor incense burning and glutathione S -transferase (GST) genetic polymorphisms on asthma and wheeze. In 2007, 3,764 seventh-grade schoolchildren (mean± sd age 12.42±0.65 yrs) were evaluated using a standard questionnaire for information about respiratory symptoms and environmental exposures. Multiple logistic regressions were performed to assess the association between GST polymorphisms and incense burning frequency on asthma and wheeze, after adjusting for potential confounders. The frequency of incense burning at home was associated with increased risk of current asthma (p = 0.05), medication use (p = 0.03) and exercise wheeze (p = 0.001). GSTθ1 ( GSTT1 ) null genotypes were associated with current asthma (OR 1.43, 95% CI 1.00–2.04) and medication use (OR 1.46, 95% CI 1.01–2.22). GSTT1 showed a significant interactive effect with incense burning on current asthma, current wheeze and nocturnal wheeze. The frequency of incense burning was associated with increased risk of current asthma, medication use, lifetime wheeze, nocturnal wheeze and exercise wheeze in an exposure–response manner among children with GSTT1 null genotype (p&lt;0.05). Incense burning is a risk factor for asthma and wheezing, especially in GSTT1 genetically susceptible children.
EMu: probabilistic inference of mutational processes and their localization in the cancer genome
Authors: Andrej Fischer, Christopher JR Illingworth, Peter J Campbell, Ville Mustonen
Journal: Genome biology (2013)

Abstract The spectrum of mutations discovered in cancer genomes can be explained by the activity of a few elementary mutational processes. We present a novel probabilistic method, EMu, to infer the mutational signatures of these processes from a collection of sequenced tumors. EMu naturally incorporates the tumor-specific opportunity for different mutation types according to sequence composition. Applying EMu to breast cancer data, we derive detailed maps of the activity of each process, both genome-wide and within specific local regions of the genome. Our work provides new opportunities to study the mutational processes underlying cancer development. EMu is available at http://www.sanger.ac.uk/resources/software/emu/ .
The development of the L-QoL: a quality-of-life instrument specific to systemic lupus erythematosus
Authors: L C Doward, S P McKenna, D Whalley, A Tennant, B Griffiths, P Emery, D J Veale
Journal: Annals of the Rheumatic Diseases (2008)

Complex diseases, such as systemic lupus erythematosus (SLE), present dilemmas over choice of outcome measures. Using a battery of instruments to capture the impact of different impairments or activity limitations experienced does not provide assessment of the wider impact on quality of life (QoL). This paper describes the development and testing of a new instrument to measure QoL in systemic lupus erythematosus (L-QoL).The development combines theoretical strengths of the needs-based QoL model with statistical and diagnostic powers of the Rasch model. Content was derived from in-depth interviews with relevant patients. Cognitive debriefing interviews assessed face and content validity. Rasch analysis was applied to data from an initial postal survey to remove misfitting items. A second postal survey assessed scaling properties, reliability, internal consistency and validity.A 55-item questionnaire was derived from interview transcripts. Cognitive debriefing confirmed acceptability. Rasch analysis of postal survey data (n = 95) removed misfitting items. A second postal survey (n = 93), produced a 25-item version with good item fit and stability, excellent test-retest reliability (0.92), internal consistency (0.92) and strict unidimensionality.It is concluded that the L-QoL should prove a valuable instrument for assessing patient-based outcome in clinical trials and practice.