tbuckley/cabot-search huggingface dataset:
Headaches and Neuroimaging
Authors: Randolph W. Evans
Journal: JAMA Internal Medicine (2015)

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Forecast: Rough Seas for Leukemia
Authors: David M. Hockenbery
Journal: Cancer Discovery (2014)

Abstract Summary: Expression of BCL-2, BCL-XL, and MCL-1 in acute myelogenous leukemia is highly variable. Cellular BH3 profiling can help decide which are likely to respond to BCL-2–targeted BH3 mimetics. Cancer Discov; 4(3); 278–9. ©2014 AACR. See related article by Pan et al., p. 362
Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma
Authors: C M Wright
Journal: Gut (2004)

Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC.To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC.A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years.DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at > or =40% of markers, MSS as no instability, and MSI-L as instability at >0% but <40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival.Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1-3.6)).Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.
Elevated serum interferon-gamma in atopic asthma correlates with increased airways responsiveness and circadian peak expiratory flow variation
Authors: NH ten Hacken, Y Oosterhoff, HF Kauffman, L Guevarra, T Satoh, DJ Tollerud, DS Postma
Journal: European Respiratory Journal (1998)

Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an important role in chronic airway inflammation in asthmatic subjects. Increased airways responsiveness and nocturnal airway obstruction are important clinical manifestations of asthma. The aim of this study was to investigate whether IL-4, IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic asthmatics and eight nonatopic healthy subjects were determined at 16:00 and 04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method. The clinical manifestation of asthma was determined by assessment of the degree of airway obstruction, airways responsiveness to methacholine and severity of nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were significantly higher in asthmatic subjects as compared to healthy controls, both at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points correlated significantly with the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= - 0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no relationship was found between the levels of IL-4 and IL-5 and the parameters of clinical manifestation of asthma. The results suggest that the serum interferon-gamma level is a reflection of the severity of airway inflammation in atopic asthma. More studies are needed to detect the cellular sources and to clarify the exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.
Intronic motif pairs cooperate across exons to promote pre-mRNA splicing
Authors: Shengdong Ke, Lawrence A Chasin
Journal: Genome biology (2010)

Abstract Background A very early step in splice site recognition is exon definition, a process that is as yet poorly understood. Communication between the two ends of an exon is thought to be required for this step. We report genome-wide evidence for exons being defined through the combinatorial activity of motifs located in flanking intronic regions. Results Strongly co-occurring motifs were found to specifically reside in four intronic regions surrounding a large number of human exons. These paired motifs occur around constitutive and alternative exons but not pseudo exons. Most co-occurring motifs are limited to intronic regions within 100 nucleotides of the exon. They are preferentially associated with weaker exons. Their pairing is conserved in evolution and they exhibit a lower frequency of single nucleotide polymorphism when paired. Paired motifs display specificity with respect to distance from the exon borders and in constitutive versus alternative splicing. Many resemble binding sites for heterogeneous nuclear ribonucleoproteins. Specific pairs are associated with tissue-specific genes, the higher expression of which coincides with that of the pertinent RNA binding proteins. Tested pairs acted synergistically to enhance exon inclusion, and this enhancement was found to be exon-specific. Conclusions The exon-flanking sequence pairs identified here by genomic analysis promote exon inclusion and may play a role in the exon definition step in pre-mRNA splicing. We propose a model in which multiple concerted interactions are required between exonic sequences and flanking intronic sequences to effect exon definition.
Impaired Angiogenesis in the Remnant Kidney Model
Authors: DUK-HEE KANG, ALISON H. JOLY, SE-WOONG OH, CHRISTIAN HUGO, DONTSCHO KERJASCHKI, KATHERINE L. GORDON, MARILDA MAZZALI, J. ASHLEY JEFFERSON, JEREMY HUGHES, KIRSTEN M. MADSEN, GEORGE F. SCHREINER, RICHARD J. JOHNSON
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Few studies have examined the role of the microvasculature in progressive renal disease. It was hypothesized that impaired angiogenesis might occur in the diseased kidney and could contribute to renal scarring. Progressive renal disease was induced in rats by 5/6 renal ablation and those rats were compared with sham-operated control animals at multiple time points, for examination of changes in the microvasculature and the expression of angiogenic factors. An early angiogenic response was documented in remnant kidneys, with increases in the proliferation of peritubular (1 wk) and glomerular (2 wk) endothelial cells. Subsequently, however, there was a decrease in endothelial cell proliferation, which was reduced to levels below those of sham-treated animals, in conjunction with interstitial expression of the antiangiogenic factor thrombospondin-1 (TSP-1) and decreased tubular expression of the proangiogenic factor vascular endothelial growth factor (VEGF). Both the increase in TSP-1 expression and the loss of VEGF expression were correlated with capillary loss and the development of glomerulosclerosis and interstitial fibrosis. Progressive macrophage infiltration was correlated both spatially and quantitatively with the sites of absent or diminished VEGF expression. In addition, macrophage-associated cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) inhibited VEGF mRNA expression and protein secretion by cultured tubular epithelial cells of the medullary thick ascending limb, under both normoxic and hypoxic conditions. Impaired angiogenesis characterizes the remnant kidney model and is correlated with progression. The impaired angiogenesis may be mediated by alterations in the renal expression of TSP-1 and VEGF, with the latter being regulated by macrophage-associated cytokines.
Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance
Authors: Otavio R. Coelho-Filho, Ravi V. Shah, Richard Mitchell, Tomas G. Neilan, Heitor Moreno, Bridget Simonson, Raymond Kwong, Anthony Rosenzweig, Saumya Das, Michael Jerosch-Herold
Journal: Circulation (2013)

Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy.
S113 The effect of small airways disease and emphysema on the association between smoking and lung function, and bronchodilator response
Authors: B. D. Patel, H. O. Coxson, P. G. Camp, S. G. Pillai, A. G. Agusti, P. M. Calverley, C. F. Donner, B. J. Make, N. L. Muller, S. I. Rennard, J. Vestbo, E. F. Wouters, W. H. Anderson, P. D. Pare, R. D. Levy, E. K. Silverman, D. A. Lomas
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> The airflow limitation of COPD results from small airway disease and emphysema. These phenotypes are likely to have independent genetic risk factors. It is not known if the heterogeneity of COPD accounts for the relatively weak association between pack-years smoked and forced expiratory volume in 1 s (FEV<sub>1</sub>) seen within smoking populations, or bronchodilator response (BDR). This study aimed to assess the effect of these phenotypes on the association between smoking and FEV<sub>1</sub> and on BDR. <h3>Method</h3> The international COPD genetics network is a multi-centre study aimed at identifying genes that predispose to COPD, in which high resolution computed tomography (HRCT) was used to quantify components of the COPD phenotype: (i) emphysema detected by radiologists (RE), (ii) emphysema assessed as per cent low-attenuation area (%LAA) and (iii) airway wall thickness (AWT) for airways with an internal perimeter of 10 mm (Pi10), 20 mm (Pi20), and average per cent wall area (WA%). They were then assessed for their effect on the association between smoking and lung function (FEV<sub>1</sub>% predicted (FEV<sub>1</sub>%)), and on BDR. <h3>Results</h3> RE data were available for 1159 individuals, 745 had complete data for Pi10, Pi20, AWT% and %LAA. The association between pack-years smoked and FEV<sub>1</sub>% was greater in those without (r=−0.41), compared to those with, RE (r=−0.12, p&lt;0.001 for difference in effect). AWT and RE correlated with FEV<sub>1</sub>% but had different relationships with smoking; AWT was positively associated with pack-years but there was no relationship between RE severity and pack-years smoked. RE, %LAA and AWT made independent contributions to FEV<sub>1</sub>%. Post-bronchodilator increase in FEV<sub>1</sub> was inversely associated with severity of RE (Abstract S113 Table 1), even after adjustment for pre-bronchodilator FEV<sub>1</sub> (p&lt;0.01). BDR was also inversely associated with %LAA (p=0.02, and p≤0.05 adjusted for baseline FEV<sub>1</sub>). <h3>Conclusion</h3> The AWT component of COPD, but not the severity of RE, increases with pack-years smoked, and the association between pack-years and FEV1% is greatest in those with an airway predominant phenotype. This suggests different gene-smoking interactions between phenotypes. RE and %LAA independently contribute to FEV1% and therefore measure different components of emphysema, however both were inversely associated with BDR.
Cancer Stem Cells in the Central Nervous System – A Critical Review
Authors: Lars Prestegarden, Per Øyvind Enger
Journal: Cancer Research (2010)

The cancer stem cell hypothesis postulates that tumors arise from, and are maintained by, a small subpopulation of cancer stem cells. This concept has recently become increasingly controversial, following a series of conflicting results. The cell-surface epitope CD133 has been proposed as a brain cancer stem cell marker, whereas a growing number of studies clearly show a tumorigenic potential among CD133(-) cells as well. Diverging results suggest that assays for isolating cancer stem cells impose a selection bias on which cells are defined as cancer stem cells. Here, we highlight some recent developments, with an emphasis on reports that call for caution in the acceptance of the brain cancer stem cell hypothesis.
Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn's disease
Authors: Ana Gutiérrez, Michael Scharl, Laura Sempere, Ernst Holler, Pedro Zapater, Isabel Almenta, José M González-Navajas, José Such, Reiner Wiest, Gerhard Rogler, Rubén Francés
Journal: Gut (2013)

The development of albuminuria in diabetics is closely associated with an enhanced risk of renal and cardiovascular disease. However, the role of albuminuria in the pathogenesis of these clinical conditions remains controversial. Whether albuminuria is simply a biomarker or qualifies as a surrogate endpoint for cardiorenal disease has wide-ranging implications from the monitoring and treatment of patients to the design of clinical trials and drug development. We critically review available data to determine whether the association between albuminuria and cardiorenal disease is causative. Current evidence suggests the significance of albuminuria depends on its severity (degree or level) and on the specific clinical outcome under consideration. For diabetic kidney disease, there is convincing epidemiologic and experimental evidence to assign clinical albuminuria status as a surrogate endpoint, but for lower levels of albuminuria (microalbuminuria and normoalbuminuria), the evidence is inconclusive or not available. Albuminuria of any degree is unlikely to be causally related to diabetic cardiovascular disease, but its onset might be useful to identify those subjects at cardiovascular risk and to detect and treat other modifiable risk factors.
Sudden Cardiac Arrest Associated with Early Repolarization
Authors: Michel Haïssaguerre, Nicolas Derval, Frederic Sacher, Laurence Jesel, Isabel Deisenhofer, Luc de Roy, Jean-Luc Pasquié, Akihiko Nogami, Dominique Babuty, Sinikka Yli-Mayry, Christian De Chillou, Patrice Scanu, Philippe Mabo, Seiichiro Matsuo, Vincent Probst, Solena Le Scouarnec, Pascal Defaye, Juerg Schlaepfer, Thomas Rostock, Dominique Lacroix, Dominique Lamaison, Thomas Lavergne, Yoshifusa Aizawa, Anders Englund, Frederic Anselme, Mark O'Neill, Meleze Hocini, Kang Teng Lim, Sebastien Knecht, George D Veenhuyzen, Pierre Bordachar, Michel Chauvin, Pierre Jais, Gaelle Coureau, Genevieve Chene, George J Klein, Jacques Clémenty
Journal: New England Journal of Medicine (2008)

Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest.We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects.Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008).Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.
Relation Between Gastroesophageal Reflux Symptoms and Socioeconomic Factors: A Population-Based Study (the HUNT Study)
Authors: Catarina Jansson, Helena Nordenstedt, Saga Johansson, Mari-Ann Wallander, Roar Johnsen, Kristian Hveem, Jesper Lagergren
Journal: Clinical Gastroenterology and Hepatology (2007)
Association of the Alzheimer's Gene<i>SORL1</i>With Hippocampal Volume in Young, Healthy Adults
Authors: Janita Bralten, Alejandro Arias-Vásquez, Remco Makkinje, Joris A. Veltman, Han G. Brunner, Guillén Fernández, Mark Rijpkema, Barbara Franke
Journal: American Journal of Psychiatry (2011)

Alzheimer's disease is among the most common neurodegenerative disorders. The SORL1 (sortilin receptor 1) gene is associated with the disease, but different variants seem to contribute. The authors used a gene-wide approach to test whether SORL1 is associated with volume of the hippocampus, one of the first structures to be affected by Alzheimer's disease in young, healthy individuals, in an attempt to map potential pathways from gene to disease.Individuals were genotyped using an array-based method, and a total of 117 single nucleotide polymorphisms (SNPs) in and surrounding SORL1 were included in the analysis. Through the use of a brain segmentation protocol, SNP-by-SNP and gene-wide associations with bilateral hippocampal volume were assessed in two large, independent samples consisting of 446 (discovery cohort) and 490 (replication cohort) healthy young individuals.Significant association of the SORL1 gene with hippocampal volume was observed in both the discovery and replication samples as well as in the combined sample. The gene-wide association was independent of the apolipoprotein E genotype and resistant to removal of four significantly associated single SNPs.This study provides the first evidence that the SORL1 gene is associated with differences in hippocampal volume in young, healthy adults. It is demonstrated that gene-wide analysis techniques may overcome power problems caused by allelic heterogeneity in association studies. The results support the hypothesis that the SORL1 gene contributes to an increased risk for Alzheimer's disease through effects on hippocampal volume.
The Healthy Women Bias and Hormone Replacement Therapy in Women With Type 2 Diabetes
Authors: Carlos Alberto Aguilar-Salinas, Eduardo García-García, Francisco J. Gómez Pérez, Juan A. Rull
Journal: Diabetes Care (2002)

A cross-sectional study by Ferrara et al. (1), recently published in Diabetes Care suggests that hormone replacement therapy (HRT) is associated with a decreased HbA1c level in women with diabetes. The “healthy women bias” always becomes an issue to be discussed in cross-sectional studies related with HRT. It is well known that women willing to initiate and continue taking any form of HRT are usually more concerned about their health, more educated, visit their doctors more often, and have lower blood pressure and lipid levels. Furthermore, compared with the rest of women, they are physically trained and usually …
HEREDITARY ACHONDROPLASIA IN THE RABBIT
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1945)

An achondroplastic condition in the rabbit has been described. It is present at birth and is characterized by size reduction, by a disproportion of bodily parts, most marked in the extremities, and by an invariably lethal effect. The animals are still-born or die very shortly after birth. In physical appearance and in the character of the skeletal changes as shown by x-ray photographs, achondroplasia in the rabbit has a remarkable resemblance to the disease in man and in cattle and dogs. The condition which first occurred in offspring of pure bred Havana rabbits is inherited. In anticipation of the later discussion of this phase of the study (13), it can be stated that the mode of inheritance is on the basis of a simple recessive unit factor and that the appearance of non-achondroplastic transmitters (heterozygotes) is that of normal animals.
Mental Illness in the Biological and Adoptive Families of Adopted Schizophrenics
Authors: SEYMOUR S. KETY, DAVID ROSENTHAL, PAUL H. WENDER, FINI SCHULSINGER
Journal: American Journal of Psychiatry (1971)

Adoption has been used as a means of separating genetic and environmental factors in the transmission of schizophrenia among family members. In the study reported here, a significantly higher than usual prevalence of schizophrenia-related illness was found among the biological relatives of adopted schizophrenics, but not among their adoptive relatives. The findings support a genetic transmission of vulnerability to schizophrenia, but also imply the requirement of nongenetic, environmental factors for the development of clinical schizophrenic illness.