tbuckley/cabot-search huggingface dataset:
Air Trapping and Airflow Obstruction in Newborn Cystic Fibrosis Piglets
Authors: Ryan J. Adam, Andrew S. Michalski, Christian Bauer, Mahmoud H. Abou Alaiwa, Thomas J. Gross, Maged S. Awadalla, Drake C. Bouzek, Nicholas D. Gansemer, Peter J. Taft, Mark J. Hoegger, Amit Diwakar, Matthias Ochs, Joseph M. Reinhardt, Eric A. Hoffman, Reinhard R. Beichel, David K. Meyerholz, David A. Stoltz
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup.Objectives: To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis.Methods: On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro–computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods.Measurements and Main Results: On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes.Conclusions: The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities.
Urinary excretion of factor VIII after renal transplantation.
Authors: Z M Ruggeri, Y B Gordon, N Ardaillou, M J Larrieu, A Tarantino, R Coppola, C Ponticelli, P M Mannucci
Journal: BMJ (1979)

The urinary excretion of factor-VIII-related antigen (VIIIRAg) was measured in 72 patients with kidney transplants and compared with that of two end-products of fibrin-fibrinogen lysis (fragments D and E) to assess their usefulness in monitoring the onset of rejection episodes. Specific and sensitive radioimmunoassays were used to measure the three proteins. Unconcentrated urine samples of 24-hour collections were obtained from 20 healthy subjects, 48 patients with stable transplants, and 24 patients with recent transplants serially followed up from the day of transplantation. Factor VIIIRAg and fragments E and D were not detectable in the urine from healthy subjects but were present in 39%, 60%, and 100% respectively of samples from patients with stable transplants. During 33 acute rejection episodes in 19 patients with recent transplants factor VIIIRAg and fragments E and D were significantly increased above the values observed in patients with stable transplants in 82%, 73%, and 64% of samples respectively; in patients with recent transplants showing no clinical sign of rejection increased excretion of these proteins was observed in 11%, 26%, and 22% of samples respectively. The presence of factor VIIIRAg in urine from patients with kidney allografts suggests that endothelial cell-factor VIII-platelet interactions might pay a key part in the pathogenesis of acute rejection. The results suggest that the assay of factor VIIIRAg in urine is more useful than assays of fragments D and E as a corroborative index of transplant rejection.
Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens.
Authors: S Macphail, O Stutman
Journal: The Journal of Experimental Medicine (1982)

Normal mouse spleen cells are not capable of mounting a primary cytotoxic T lymphocyte (Tc) response to non-H-2 alloantigens in vitro, although a good secondary H-2-restricted response is observable after in vivo immunization of the responder animals. Suppressor cells are generated in such a primary responses provided a Mls incompatibility exists between the responder and stimulator. These suppressors are not antigen specific, are Thy-1+, Lyt-1+, 2-, I-J-, and are highly radiosensitive. The suppressor cell precursors in normal spleen express the same phenotype. These suppressor cells are probably implicated in the lack of a primary Tc response in a primary mixed lymphocyte reaction across non-H-2 incompatibilities that include an Mls difference.
Genome-wide association studies are coming for human infectious diseases
Authors: Sonia Davila, Martin L Hibberd
Journal: Genome Medicine (2009)

A genetic contribution to infectious disease in human populations has long been suspected and is now supported by more than 50 years of epidemiological evidence showing, for example, infection rates to be much higher than disease rates. In successful family studies of high-penetrance effects, single gene mutations have been identified that reveal a molecular mechanism leading to increased risk of a specific infectious disease. However, in population-based studies, genetic variants conferring host susceptibility to various infectious diseases have been difficult to uncover. Although mutations such as that in the CCR5 gene, which confers protection against HIV infection, have been reliably discovered, polymorphisms affecting larger proportions of a population have been hard to prove definitively. The recent arrival of the genome-wide association study format, currently being applied to Kawasaki disease, tuberculosis, malaria, HIV, dengue and others, gives us hope that these challenges can finally be met, with implications for population-based treatment and prognosis strategies.
Meal planning and nutritional supplements use among elite bodybuilders in Taiwan
Authors: Margaret Jip Kuo
Journal: British Journal of Sports Medicine (2010)

The interaction between exercise and nutrition is important for bodybuilders. The intake of food during post-exercise recovery is necessary for hypertrophy to occur. Therefore, the current survey was performed to assess information regarding the meal planning and use of such supplements among elite bodybuilders in Taiwan. Method Thirty-four (26 male and 8 female) bodybuilders completed a questionnaire which conducted to examine the source of information, meal planning and usage of nutritional supplements. Result All the bodybuilders ingest protein and carbohydrate following exercise to attain a positive protein balance and maximise their skeletal muscle adaptive response. The prevalence of supplement use was 65% and nine different products were used. Female athletes were more likely to take supplements for their health or because of an inadequate diet, while male reported taking supplements to improve strength and power, and for weight and muscle gain. Females were more likely to take calcium, multivitamins and essence of chicken. And males had significant intake for Siberian ginseng, amino acids, glutamine, weight gainers and whey protein. The most frequently used supplements overall were sports drinks (88%), creatine (74%), whey protein (65%), energy drinks (53%), vitamin C (57%), vitamin B complex (62%) and multivitamin (44%). Before using a product, 72% sought information, usually from the media and internet, a store nutritionist, coaches, friends and fellow bodybuilders. However, many did not know where to obtain reliable information and 82% were also unaware that supplementation can have adverse effects. Conclusion Although the supplement use is common among the bodybuilders in Taiwan, many do not have accurate information about these products. Hence, there is an urgent need to provide athletes nutritional education and scientifically sound guidance by leading sport organisations is required.
Conditional inactivation of <i>Fbxw7</i> impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis
Authors: Ichiro Onoyama, Ryosuke Tsunematsu, Akinobu Matsumoto, Taichi Kimura, Ignacio Moreno de Alborán, Keiko Nakayama, Keiichi I. Nakayama
Journal: The Journal of Experimental Medicine (2007)

Cell proliferation is strictly controlled during differentiation. In T cell development, the cell cycle is normally arrested at the CD4(+)CD8(+) stage, but the mechanism underlying such differentiation-specific exit from the cell cycle has been unclear. Fbxw7 (also known as Fbw7, Sel-10, hCdc4, or hAgo), an F-box protein subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle, such as c-Myc, c-Jun, cyclin E, and Notch. FBXW7 is often mutated in a subset of human cancers. We have now achieved conditional inactivation of Fbxw7 in the T cell lineage of mice and found that the cell cycle is not arrested at the CD4(+)CD8(+) stage in the homozygous mutant animals. The mutant mice manifested thymic hyperplasia as a result of c-Myc accumulation and eventually developed thymic lymphoma. In contrast, mature T cells of the mutant mice failed to proliferate in response to mitogenic stimulation and underwent apoptosis in association with accumulation of c-Myc and p53. These latter abnormalities were corrected by deletion of p53. Our results suggest that Fbxw7 regulates the cell cycle in a differentiation-dependent manner, with its loss resulting in c-Myc accumulation that leads to hyperproliferation in immature T cells but to p53-dependent cell-cycle arrest and apoptosis in mature T cells.
Pitfalls in gastrointestinal permeability measurement in ICU patients
Authors: Falco Hietbrink, Marc G. H. Besselink, Willem Renooij, Luke P. H. Leenen
Journal: Intensive Care Medicine (2007)

Sir: It is hypothesized that increased intestinal permeability can induce or enhance septic complications in intensive care patients by facilitating bacterial translocation. A reliable and safe detection method would aid in identifying patients with increased intestinal permeability. Intestinal permeability has frequently been measured by tests based on the differential sugar absorption principle. In these tests the ratio of urinary recovery after orally administration of a small permeant sugar probe and large sugar probe, impermeant in the uncompromised intestine, is used as an indication of intestinal permeability [1]. The principle of these tests is that premucosal factors (i.e., gastric retention) and postmucosal factors (i.e., metabolism and renal function) are excluded because these should affect both probes similarly.Therefore only mucosal factors (i.e., intestinal permeability) is indicated. The most commonly used test is the lactulose mannitol test (LMT). Oudemans-van Straaten et al. [2] identified confounding factors when performing the LMT in ICU patients. Their study was conducted in severely ill patients with multiple organ failure. The LMT could still be applicable in patients with milder disease.

We performed the LMT on trauma patients admitted to an ICU, including all patients, with a variety of injury severity. Thirteen trauma patients were included who underwent three tests each. The trauma patients' median Injury Severity Score was 24 (range 16–38). Renal function was within normal range in all patients (creatinine < 120 μmol/l; ureum < 7.5 μmol/l). In 19 tests (61%) confounding factors were identified. Of the confounding factors 53% were therapy related (i.e., mannitol use as therapeutic agent or in saline adenosine glucose mannitol). In the remaining 47% of biased tests, the factors consisted of administering problems (i.e., stomach retention).

Thus two groups of confounding factors cause a problem: (a) the use of test substances for clinical applications and (b) administering problems with the test solution. The first problem affects the probes differently, thus causing invalid test results. This can be overcomeby discarding mannitol as probe. The administering problem affects the two probes similarly, and thus the ratio remains constant. In the case of gastric retention probes do not reach the intestine and cannot be measured in urine. A solution would be to administer the test fluid in the small intestine by a nasoduodenal tube.

We conclude, and stress this as a warning to future researchers, that the LMT is inappropriate not only for patients with multiple organ failure but also for trauma patients in an ICU setting (without organ failure).
The Role of Dopamine in Attentional and Memory Biases for Emotional Information
Authors: Ayana A Gibbs, Kris H Naudts, Edgar P Spencer, Anthony S David
Journal: American Journal of Psychiatry (2007)

Objective: Cognitive models suggest that biased processing of emotional information may play a role in the genesis and maintenance of psychotic symptoms. The role of dopamine and dopamine antagonists in the processing of such information remains unclear. The authors investigated the effect of a dopamine antagonist on perception of, and memory for, emotional information in healthy volunteers. Method: Thirty-three healthy male volunteers were randomly assigned to a single-blind intervention of either a single dose of the dopamine D 2 /D 3 antagonist amisulpride or placebo. An attentional blink task and an emotional memory task were then administered to assess the affective modulation of attention and memory, respectively. Results: A significant interaction was observed between stimulus valence and drug on recognition memory accuracy; further contrasts revealed enhanced memory for aversive-arousing compared with neutral stimuli in the placebo but not the amisulpride group. No effect of amisulpride was observed on the perception of emotional stimuli. Conclusions: Amisulpride abolished the enhanced memory for emotionally arousing stimuli seen in the placebo group but had no effect on the perception of such stimuli. These results suggests that dopamine plays a significant role in biasing memory toward emotionally salient information and that dopamine antagonists may act by attenuating this bias.
The heme oxygenase 1 product biliverdin interferes with hepatitis C virus replication by increasing antiviral interferon response
Authors: Elisabeth Lehmann, Walid Hamdy El-Tantawy, Matthias Ocker, Ralf Bartenschlager, Volker Lohmann, Said Hashemolhosseini, Gisa Tiegs, Gabriele Sass
Journal: Hepatology (2009)

The anti-inflammatory and antiapoptotic heme degrading enzyme heme oxygenase-1 (HO-1) has been shown recently to interfere with replication of hepatitis C virus (HCV). We investigated the effect of HO-1 products carbon monoxide (CO), iron and biliverdin on HCV replication using the replicon cell lines Huh-5-15 and LucUbiNeo-ET, stably expressing HCV proteins NS3 through NS5B. Incubation of these cell lines in the presence of the CO donor methylene chloride transiently reduced HCV replication, whereas an increase of iron in cell culture by administration of FeCl(3) or iron-saturated lactoferrin did not interfere with HCV replication. Likewise, depletion of iron by deferoxamine during induction of HO-1 by cobalt-protoporphyrin IX did not restore HCV replication. The most prominent effect was observed after incubation of replicon cell lines in the presence of biliverdin. Biliverdin seems to interfere with HCV replication-mediated oxidative stress by inducing expression of antiviral interferons, such as interferon alpha2 and alpha17.The antioxidant biliverdin reduces HCV replication in vitro by triggering the antiviral interferon response and might improve HCV therapy in the future.
Birth-and-Death Evolution with Strong Purifying Selection in the Histone H1 Multigene Family and the Origin of orphon H1 Genes
Authors: José M. Eirín-López, Ana M. González-Tizón, Andrés Martínez, Josefina Méndez
Journal: Molecular Biology and Evolution (2004)

Histones are small basic nuclear proteins with critical structural and functional roles in eukaryotic genomes. The H1 multigene family constitutes a very interesting histone class gathering the greatest number of isoforms, with many different arrangements in the genome, including clustered and solitary genes, and showing replication-dependent (RD) or replication-independent (RI) expression patterns. The evolution of H1 histones has been classically explained by concerted evolution through a rapid process of interlocus recombination or gene conversion. Given such intriguing features, we have analyzed the long-term evolutionary pattern of the H1 multigene family through the evaluation of the relative importance of gene conversion, point mutation, and selection in generating and maintaining the different H1 subtypes. We have found the presence of an extensive silent nucleotide divergence, both within and between species, which is always significantly greater than the nonsilent variation, indicating that purifying selection is the major factor maintaining H1 protein homogeneity. The results obtained from phylogenetic analysis reveal that different H1 subtypes are no more closely related within than between species, as they cluster by type in the topologies, and that both RD and RI H1 variants follow the same evolutionary pattern. These findings suggest that H1 histones have not been subject to any significant effect of interlocus recombination or concerted evolution. However, the diversification of the H1 isoforms seems to be enhanced primarily by mutation and selection, where genes are subject to birth-and-death evolution with strong purifying selection at the protein level. This model is able to explain not only the generation and diversification of RD H1 isoforms but also the origin and long-term persistence of orphon RI H1 subtypes in the genome, something that is still unclear, assuming concerted evolution.
The Injection of Capillaries, Arterioles, and Arteries in the Ventricles of the Human Heart by a Radio-opaque Medium
Authors: G. Farrer-Brown
Journal: Cardiovascular Research (1968)

The method used to study a series of hearts after death by injection with a radio-opaque media, Chromopaque, and microradiography using Kodak High Resolution plates is described. The medium could be confined to either small arteries or arterioles or allowed to fill capillaries. Considerably greater magnification of the small vessels was achieved than has hitherto been possible.
MYC Regulation of CHK1 and CHK2 Promotes Radioresistance in a Stem Cell-like Population of Nasopharyngeal Carcinoma Cells
Authors: Wen-Jun Wang, Si-Pei Wu, Jia-Bin Liu, Yong-Sheng Shi, Xue Huang, Qian-Bing Zhang, Kai-Tai Yao
Journal: Cancer Research (2012)

Radiotherapy is the most successful nonsurgical treatment for nasopharyngeal carcinoma (NPC). Despite this, the prognosis remains poor. Although NPCs initially respond well to a full course of radiation, recurrence is frequent. The cancer stem cell (CSC) hypothesis provides a framework for explaining the discrepancy between the response of NPC to therapy and the poor survival rate. In this study, a stem cell-like subpopulation (PKH26+) was identified in NPC cell lines using a label-retention technique. PKH26+ cells were enriched for clonogenicity, sphere formation, side-population cells, and resistance to radiotherapy. Using genomic approaches, we show that the proto-oncogene c-MYC (MYC) regulates radiotolerance through transcriptional activation of CHK1 (CHEK1) and CHK2 (CHEK2) checkpoint kinases through direct binding to the CHK1 and CHK2 promoters. Overexpression of c-MYC in the PKH26+ subpopulation leads to increased expression of CHK1 and CHK2 and subsequent activation of the DNA-damage-checkpoint response, resulting in radioresistance. Furthermore, loss of CHK1 and CHK2 expression reverses radioresistance in PKH26+ (c-MYC high expression) cells in vitro and in vivo. This study elucidates the role of the c-MYC-CHK1/CHK2 axis in regulating DNA-damage-checkpoint responses and stem cell characteristics in the PKH26+ subpopulation. Furthermore, these data reveal a potential therapeutic application in reversal of radioresistance through inhibition of the c-MYC-CHK1/CHK2 pathway.
An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model
Authors: Stefanie A. Krumm, Dan Yan, Elise S. Hovingh, Taylor J. Evers, Theresa Enkirch, G. Prabhakar Reddy, Aiming Sun, Manohar T. Saindane, Richard F. Arrendale, George Painter, Dennis C. Liotta, Michael G. Natchus, Veronika von Messling, Richard K. Plemper
Journal: Science Translational Medicine (2014)

Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.
Fatal aortogastric fistula following fully covered metal stent placement for refractory esophageal stricture
Authors: E. van Geenen, N. Visser, J. Bonenkamp
Journal: Endoscopy (2014)

A 45-year-old woman with a history of systemic sclerosis presented with a post-anastomotic gastric tube stenosis 1 year after esophagus resection and gastric tube interposition for a ypT3N1M0 adenocarcinoma of the esophagus. She was also treated with neo-adjuvant chemoradiation therapy [1]. Endoscopy identified a post-anastomotic esophageal stenosis extending from 24 cm to 32 cm aborally. She had shown only a limited response to 23 Savary dilations and one balloon dilation in 9 months. We therefore decided to use an 18 × 12 cm fully covered metal stent (Evolution; Cook Medical Inc., Bloomington, Indiana, USA) across the stenosis.