tbuckley/cabot-search huggingface dataset:
Identification of <i>Fat4</i> and <i>Tsc22d1</i> as Novel Candidate Genes for Spontaneous Pulmonary Adenomas
Authors: Annerose Berndt, Clinton L. Cario, Kathleen A. Silva, Victoria E. Kennedy, David E. Harrison, Beverly Paigen, John P. Sundberg
Journal: Cancer Research (2011)

Genetic influences that underlie spontaneous lung oncogenesis are poorly understood. The objective of this study was to determine the genetic influences on spontaneous pulmonary adenoma frequency and severity in 28 strains of mice as part of a large-scale aging study conducted at the Jackson Aging Center (http://agingmice.jax.org/). Genome-wide association studies were conducted in these strains with both low-density (132,000) and high-density (4,000,000) panel of single-nucleotide polymorphisms (SNP). Our analysis revealed that adenomas were relatively less frequent and less severe in females than males, and that loci implicated in frequency and severity were often different between male and female mice. While some of the significant loci identified mapped to genomic locations known to be responsible for carcinogen-induced cancers (e.g., Pas1), others were unique to our study. In particular, Fat4 was influential in males and Tsc22d1 was influential in females. SNPs implicated were predicted to alter amino acid sequence and change protein function. In summary, our results suggested that genetic influences that underlie pulmonary adenoma frequency are dependent on gender, and that Fat4 and Tsc22d1 are likely candidate genes to influence formation of spontaneous pulmonary adenoma in aging male and female mice, respectively.
Intracoronary Ultrasound Longitudinal Reconstruction of a Postangioplasty Coronary Artery Dissection
Authors: I. Patrick Kay, Manel Sabate, Jurgen M. R. Ligthart, Willem J. van der Giessen, Pim J. de Feyter, Patrick W. Serruys
Journal: Circulation (1999)

A 62-year-old woman presented with unstable angina.Angiography demonstrated a severe stenosis in the distal right coronary artery (RCA), and angioplasty with stent implantation was undertaken.This was complicated by a coronary artery dissection distal to the stent that was detected by angiography and intracoronary ultrasound (ICUS).
Nocturnal Hypoxemia Predicts Incident Cardiovascular Complications in Dialysis Patients
Authors: Carmine Zoccali, Francesca Mallamaci, Giovanni Tripepi
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Nocturnal hypoxemia secondary to sleep apnea has long been implicated as a cardiovascular risk factor in renal failure, but to date there is no study that links nocturnal hypoxemia to cardiovascular outcomes in end-stage renal disease. Fifty uremic patients on regular dialysis treatment without primary sleep apnea, pulmonary diseases, or other illnesses that may cause sleep apnea underwent pulse oximetry studies during night and were followed up for 32 mo. Average nocturnal SaO 2 , minimal SaO 2 , and the number of episodes of hypoxemia were similar in patients who died during the follow-up and in patients who survived, and none of these parameters predicted all-cause mortality. Average nocturnal SaO 2 was significantly lower ( P = 0.006) in patients who had cardiovascular events during the follow-up (94.7 ± 2.9%) than in event-free patients (97.1 ± 1.3%). In a Cox model, average nocturnal SaO 2 was the second factor in rank explaining these outcomes. In this model a 1% decrease in average nocturnal SaO 2 was associated with a 33% increase in the incident risk of fatal and nonfatal cardiovascular events. Furthermore the risk of cardiovascular events was 5.05 times higher in patients with average nocturnal SaO 2 &lt;95% (95% CI 1.61 to 15.86) than in those above this threshold ( P = 0.005). This study adds weight to the hypothesis that nocturnal hypoxemia in dialysis patients represents an important cardiovascular risk factor.
Influence of Mulberry Leaf Extract on the Blood Glucose and Breath Hydrogen Response to Ingestion of 75 g Sucrose by Type 2 Diabetic and Control Subjects
Authors: Mitchell Mudra, Nacide Ercan-Fang, Litao Zhong, Julie Furne, Michael Levitt
Journal: Diabetes Care (2007)

In Asia, type 2 diabetes is treated with mulberry leaf. Studies supporting this usage include the demonstration that mulberry leaf 1 ) reduced blood glucose in normal rats (1) and rats with diabetes induced by streptozotocin (2) or alloxan (3), 2 ) reduced fasting blood glucose and A1C concentrations in 12 subjects with type 2 diabetes (4), and 3 ) relative to glybenclamide therapy, reduced fasting blood glucose, serum lipids, and lipid peroxidation indicators in subjects with type 2 diabetes (5). In the present study, we determined whether co-ingestion of mulberry extract with 75 g sucrose influenced the blood glucose response and sucrose absorption of type 2 diabetic and control subjects.

Participants included 10 healthy control subjects (aged 24–61 years) and 10 type 2 diabetic subjects without complications who were receiving oral hypoglycemic agents (aged 59–75 years; glycohemoglobin 7.1 ± 0.9% [normal <6.2%]). The study was approved by the Minneapolis VA Medical Center Human Studies Committee. Mulberry leaf extract was provided by NatureGen (San Diego, CA). Placebo (red dye #40 and caramel) was similar in color and taste to the mulberry.

At 8 a.m., subjects randomly ingested mulberry extract (1 g) or placebo plus 75 g sucrose in 500 ml hot water. The test was repeated in 1 week with the opposite …
Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples
Authors: Christian B Matranga, Kristian G Andersen, Sarah Winnicki, Michele Busby, Adrianne D Gladden, Ryan Tewhey, Matthew Stremlau, Aaron Berlin, Stephen K Gire, Eleina England, Lina M Moses, Tarjei S Mikkelsen, Ikponmwonsa Odia, Philomena E Ehiane, Onikepe Folarin, Augustine Goba, S Humarr Kahn, Donald S Grant, Anna Honko, Lisa Hensley, Christian Happi, Robert F Garry, Christine M Malboeuf, Bruce W Birren, Andreas Gnirke, Joshua Z Levin, Pardis C Sabeti
Journal: Genome biology (2014)

We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.
Brain Development in Heavy-Drinking Adolescents
Authors: Lindsay M. Squeglia, Susan F. Tapert, Edith V. Sullivan, Joanna Jacobus, M.J. Meloy, Torsten Rohlfing, Adolf Pfefferbaum
Journal: American Journal of Psychiatry (2015)

Objective: Heavy alcohol use during adolescence may alter the trajectory of normal brain development. The authors measured within-subject changes in regional brain morphometry over longer intervals and in larger samples of adolescents than previously reported and assessed differences between adolescents who remained nondrinkers and those who drank heavily during adolescence as well as differences between the sexes. Method: The authors examined gray and white matter volume trajectories in 134 adolescents, of whom 75 transitioned to heavy drinking and 59 remained light drinkers or nondrinkers over roughly 3.5 years. Each underwent MRI scanning two to six times between ages 12 and 24 and was followed for up to 8 years. The volumes of the neocortex, allocortex, and white matter structures were measured using atlas-based parcellation with longitudinal registration. Linear mixed-effects models described differences in trajectories of heavy drinkers and nondrinkers over age; secondary analyses considered the contribution of other drug use to identified alcohol use effects. Results: Heavy-drinking adolescents showed accelerated gray matter reduction in cortical lateral frontal and temporal volumes and attenuated white matter growth of the corpus callosum and pons relative to nondrinkers. These results were largely unchanged when use of marijuana and other drugs was examined. Male and female drinkers showed similar patterns of development trajectory abnormalities. Conclusions: Longitudinal analysis enabled detection of accelerated typical volume decline in frontal and temporal cortical volumes and attenuated growth in principal white matter structures in adolescents who started to drink heavily. These results provide a call for caution regarding heavy alcohol use during adolescence, whether heavy drinking is the sole cause or one of several in these alterations in brain development.
What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae?
Authors: Diana Ekman, Sara Light, Åsa K Björklund, Arne Elofsson
Journal: Genome biology (2006)

Abstract Background Most proteins interact with only a few other proteins while a small number of proteins (hubs) have many interaction partners. Hub proteins and non-hub proteins differ in several respects; however, understanding is not complete about what properties characterize the hubs and set them apart from proteins of low connectivity. Therefore, we have investigated what differentiates hubs from non-hubs and static hubs (party hubs) from dynamic hubs (date hubs) in the protein-protein interaction network of Saccharomyces cerevisiae . Results The many interactions of hub proteins can only partly be explained by bindings to similar proteins or domains. It is evident that domain repeats, which are associated with binding, are enriched in hubs. Moreover, there is an over representation of multi-domain proteins and long proteins among the hubs. In addition, there are clear differences between party hubs and date hubs. Fewer of the party hubs contain long disordered regions compared to date hubs, indicating that these regions are important for flexible binding but less so for static interactions. Furthermore, party hubs interact to a large extent with each other, supporting the idea of party hubs as the cores of highly clustered functional modules. In addition, hub proteins, and in particular party hubs, are more often ancient. Finally, the more recent paralogs of party hubs are underrepresented. Conclusion Our results indicate that multiple and repeated domains are enriched in hub proteins and, further, that long disordered regions, which are common in date hubs, are particularly important for flexible binding.
Longer Axial Length Is Protective of Diabetic Retinopathy and Macular Edema
Authors: Ryan Eyn Kidd Man, Muhammad Bayu Sasongko, Sutharssna Sanmugasundram, Theona Nicolaou, Xie Jing, Jie Jin Wang, Tien Yin Wong, Ecosse L. Lamoureux
Journal: Ophthalmology (2012)
Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment
Authors: Y. Xu, Y. Sun, L. Yao, L. Shi, Y. Wu, T. Ouyang, J. Li, T. Wang, Z. Fan, T. Fan, B. Lin, L. He, P. Li, Y. Xie
Journal: Annals of Oncology (2008)
ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells
Authors: Pingping Zhu, Yanying Wang, Lei He, Guanling Huang, Ying Du, Geng Zhang, Xinlong Yan, Pengyan Xia, Buqing Ye, Shuo Wang, Lu Hao, Jiayi Wu, Zusen Fan
Journal: Journal of Clinical Investigation (2015)

Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.
Extreme altitude transient aphasia.
Authors: E Garrido, C Javierre
Journal: British Journal of Sports Medicine (1996)

Department of Physiological Sciences, Medical School, University of Barcelona, Spain Eduardo Garrido Casimiro Javierre Severe mountain sickness, cerebral oedema, or ischaemic infarcts may occur when humans ascend to high altitude. However, neurological symptoms can occasionally be atypical. Recently, we studied a highly experienced climber who had suffered difficulties in expressing himself verbally, emitting incomprehensible sounds during a strenuous ascent to 8000 m in the Himalayas. The speech disorder, which was not associated with other neurological impairments, disappeared following a short rest. Cranial magnetic resonance imaging, performed 40 days later, showed small high intensity signals in the posterior lobes. To our knowledge, the nearest neurological episode to this case is a self report by Shipton' in 1943. Cerebral blood flow is highly sensitive to changes in carbon dioxide tension. CO2 inhalation increases brain perfusion quickly reversing many high-altitude neurologic disturbances. Hackett et al.' reported six cases of altitude cortical blindness who showed excellent response to CO2 administration. A severe fall in the arterial Pco2 (at rest approximately 10 mm Hg at 8000 m) due to intense pulmonary gas exchange during fast ascents to extreme altitude can result in non-uniform vasoconstriction and tissue distribution. This mechanism, together with an increased blood viscosity and coagulability in a high mountain environment, would increase the hypoxic insult, especially in small vessel territories of the brain. Although the precise significance and future implications of these magnetic resonance findings are not clear, the presentation and clinical evolution of this case strongly suggest a selective vasospasm of brain speech areas. Nevertheless, these imaging findings may be related to cumulative cerebral damage, as we have observed in a large number of climbers after repeated exposure to extreme altitude.3 Indeed, the increasing popularity of attempting to conquer the world's highest summits without supplementary oxygen would lead us to conjecture that such autolimited neurological episodes occur more frequently than is reported in the mountain medicine literature.
Anticytokine approaches in pulmonary fibrosis: bringing factors into focus
Authors: R. K. Coker, G. J. Laurent
Journal: Thorax (1997)

The prognosis of pulmonary fibrosis is poor and current therapies inadequate. Recent progress in understanding the mechanisms underlying the pathogenesis of this disease leads us to expect that inhibitors of cytokine and polypeptide growth factor will provide novel therapeutic agents. This paper outlines the role of cytokines in the pathogenesis of pulmonary fibrosis and concludes that there are compelling reasons to explore anticytokine therapeutic approaches. It also proposes criteria that will enable us to evaluate such agents in vivo and suggests approaches which might overcome the obstacles presented by control mechanisms which recruit a multiplicity of factors.
Smoking Cessation Among Diabetic Patients in Kerala, India: 1-Year Follow-up Results From a Pilot Randomized Controlled Trial
Authors: Kavumpurathu Raman Thankappan, Gomathy Krishnakurup Mini, Meenu Hariharan, Gadadharan Vijayakumar, Prabhakaran Sankara Sarma, Mark Nichter
Journal: Diabetes Care (2014)

Considering the adverse health effects of smoking, the American Diabetes Association recommends smoking cessation among diabetic patients (1). One-year follow-up data on smoking cessation among diabetic patients are not available (2). We conducted this study to find the effectiveness of diabetes-specific smoking cessation counseling by a nondoctor health professional (NDHP) in addition to quitting advice by a doctor at 1 year. We recruited 224 adult male diabetic patients aged ≥18 years who smoked in the previous month from two diabetes clinics of Kerala for our randomized controlled trial. They were randomized into two equal groups: intervention-1 and intervention-2. Patients in both groups were asked and advised by a doctor to quit smoking and education materials on smoking-related complications were provided. The intervention-2 group received four additional diabetes-specific 30-min smoking cessation counseling sessions at baseline and 1, 3, and 6 months …
Immune Escape of Tumors in Vivo by Expression of Cellular Flice-Inhibitory Protein
Authors: Jan Paul Medema, Joan de Jong, Thorbald van Hall, Cornelis J.M. Melief, Rienk Offringa
Journal: The Journal of Experimental Medicine (1999)

The antiapoptotic protein cellular FLICE (Fas-associated death domain–like IL-1β–converting enzyme) inhibitory protein (cFLIP) protects cells from CD95(APO-1/Fas)-induced apoptosis in vitro and was found to be overexpressed in human melanomas. However, cytotoxic T cell–induced apoptosis, which is critically involved in tumor control in vivo, is not inhibited by cFLIP in vitro, as only CD95- and not perforin-dependent lysis is affected. This calls into question whether cFLIP is sufficient to allow escape from T cell–dependent immunity. Using two murine tumors, we directly demonstrate that cFLIP does result in escape from T cell immunity in vivo. Moreover, tumor cells are selected in vivo for elevated cFLIP expression. Therefore, our data indicate that CD95-dependent apoptosis constitutes a more prominent mechanism for tumor clearance than has so far been anticipated and that blockade of this pathway can result in tumor escape even when the perforin pathway is operational.
Experimental cryo-irrigation of the knee joint.
Authors: S C Chen, B Helal, P A Revell, R Brocklehurst, H L Currey
Journal: Annals of the Rheumatic Diseases (1986)

Experiments have been carried out to test the feasibility of using cryo-irrigation as a means of ablating the synovium in the rheumatoid knee joint. Cryo-irrigation was performed by a cooling machine and pump, which circulated cold 200/10 centistoke (cSt) silicone through the knee joint of rabbits anaesthetised with intravenous (IV) 9Saffan9. Fluid left the joint at -5 to -10 degrees C. Sixteen normal New Zealand rabbits received cryo-irrigation of one knee joint for 10-20 minutes and were killed at one day, and one, two, and 12 weeks thereafter. Judged by radioactive sulphate incorporation there was no impairment of chondrocyte function in the articular cartilage of irrigated joints. Histological examination showed mild synovitis and some loss of staining of superficial cartilage in 6/16 irrigated joints (v 1/16 control joints). Similar treatment of rabbit joints in which the Glynn model of synovitis had been induced showed marked reduction of synovitis 14-45 days after silicone treatment. Nine of 26 animals in which synovitis was induced in both knees and cryo-irrigation performed in one knee died either immediately postoperatively or during the next week. These deaths remain unexplained. A single dog received cryo-irrigation of one knee (-6 to -9 degrees C for 22 min) and remained perfectly well up to sacrifice at six months, when the joint appeared histologically completely normal.
Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.
Authors: J Goldman, D Baldwin, A H Rubenstein, D D Klink, W G Blackard, L K Fisher, T F Roe, J J Schnure
Journal: Journal of Clinical Investigation (1979)

Five patients with fasting and(or) postprandial hypoglycemia were found to have insulin antibodies in the absence of previously documented immunization. Studies on the equilibrium-binding of insulin to the autoantibodies revealed two classes of binding sites with association constants and binding capacities analogous to those of insulin antibodies from insulin-treated diabetic patients. Similarly, no consistent differences in these parameters were found in both groups of patients with insulins of bovine, porcine, and human origin. Proinsulin (C-segment directed) antibodies capable of binding bovine or porcine proinsulin were present in 10 of 10 and 9 of 10 insulin-treated diabetics serving as controls, respectively, and, when present, provide incontrovertible evidence of exogenous insulin administration. No such antibodies could be detected in the hypoglycemic patients with autoimmune insulin antibodies. The kinetics of dissociation of the insulin-antibody complexes were consistent with the existence of two classes of antibody sites. The corresponding dissociation rate constants were large enough to predict that significant amounts of free hormone may be generated by this mechanism and provide a plausible pathogenesis for the hypoglycemia in these patients.
The Mechanism of Atrioventricular Conduction
Authors: A. M. SCHER, MARIA I. RODRIGUEZ, J. LIIKANE, A. C. YOUNG
Journal: Circulation Research (1959)

Potentials recorded at various sites in the atrioventricular (A-V) conduction system indicate that conduction is continuously electrical in nature and involves no synapse-like (i.e., chemical) conduction. The region between atrium and atrioventricular node has the slowest conduction velocity (.05 M./sec.) and lowest safety factor. Conduction through the A-V node is at about .12 M./sec. Results demonstrate shapes of potentials recorded extracellularly at various sites within the A-V node, first degree and complete block during rapid atrial stimulation, and echo-like phenomena.
Alloantigen receptors on activated T cells in mice. I. Binding of alloantigens and anti-idiotypic antibodies to the same receptors.
Authors: P H Krammer
Journal: The Journal of Experimental Medicine (1978)

B6 alloantigens in supernates from one-way mixed lymphocyte reaction (MLR) cultures of AKR T cells against B6 lymph node cells rebound specifically to (B6)AKR-T-cell blasts after overnight incubation and recovery of these blasts from trypsin treatment. A similar specificity was observed with the binding of SJL alloantigens to (SJL)AKR-T-cell blasts. In both cases, the corresponding alloantigens were rebound several-fold more efficiently than control alloantigens. In a different assay system, T-cell receptors were studied with anti-idiotypic sera. These antisera were raised by repeated injection of purified (B6)AKR-T-cell blasts into (AKR X B6)F1 hybrid mice. These F1a(AKRaB6) sera reacted with the majority of (B6)AKR-T and (B6)(AKR X SJL)F1-T-cell blasts. They also reacted with a lower, though sizable, number of (SJL)AKR-T- and (SJL)(AKR X B6)F1-T-cell blasts. No reaction was observed with (B6)SJL-T, concanavalin A-activated AKR T-cell blasts, normal B6, (AKR X B6)F1, and (AKR X SJL)F1 T cells. Normal AKR T cells were positive only minimally above background. F1a(AKRaB6) sera could be made specific for (B6)AKR-T and (B6)(AKR X SJL)F1-T-cell blasts by absorption of contaminating antibodies with (SJL)AKR-T-cell blasts. Finally, it was shown by competition experiments that the receptors on MLR-activated T-cell blasts that bind alloantigens were the same as those binding anti-idiotypic antibodies. In addition, it was found that at least a fraction of alloantibodies share common idiotypic determinants with receptors on MLR-activated T-cell blasts.