tbuckley/cabot-search huggingface dataset:
Hyperlipidemia in Coronary Heart Disease I. LIPID LEVELS IN 500 SURVIVORS OF MYOCARDIAL INFARCTION
Authors: Joseph L. Goldstein, William R. Hazzard, Helmut G. Schrott, Edwin L. Bierman, Arno G. Motulsky
Journal: Journal of Clinical Investigation (1973)

Plasma cholesterol and triglyceride levels were measured after an overnight fast in 500 consecutively studied 3-mo survivors of myocardial infarction. Virtually all patients under 60 yr of age (95% ascertainment) and a randomly chosen group of older survivors admitted to 13 Seattle hospitals during an 11 mo period were included. A comparison of their lipid values with those of 950 controls demonstrated that 31% had hyperlipidemia. These lipid abnormalities were most commonly found in males under 40 yr of age (60% frequency) and in females under 50 yr of age (60% frequency). Elevation in triglyceride levels with (7.8%) or without (15.6%) an associated elevation in cholesterol levels was three times more common in survivors than a high cholesterol level alone (7.6%). These results raise the possibility that hypertriglyceridemia may be as an important a risk factor for coronary atherosclerosis as hypercholesterolemia. The identification of hyperlipidemic survivors of myocardial infarction provided a unique source of probands for family studies designed to disclose the genetic origin of hyperlipidemia in coronary heart disease.
Relative Patterns and Rates of Evolution in Heron Nuclear and Mitochondrial DNA
Authors: Frederick H. Sheldon, Clare E. Jones, Kevin G. McCracken
Journal: Molecular Biology and Evolution (2000)

Mitochondrial cytochrome b sequence data from 15 species of herons (Aves: Ardeidae), representing 13 genera, were compared with DNA hybridization data of single-copy nuclear DNA (scnDNA) from the same species in a taxonomic congruence assessment of heron phylogeny. The two data sets produced a partially resolved, completely congruent estimate of phylogeny with the following basic structure: (Tigrisoma, Cochlearius, (((Zebrilus, (Ixobrychus, Botaurus)), (((Ardea, Casmerodius), Bubulcus), ((Egretta thula, Egretta caerulea, Egretta tricolor), Syrigma), Butorides, Nycticorax, Nyctanassa)))). Because congruence indicated similar phylogenetic information in the two data sets, we used the relatively unsaturated DNA hybridization distances as surrogates of time to examine graphically the patterns and rates of change in cytochrome b distances. Cytochrome b distances were computed either from whole sequences or from partitioned sequences consisting of transitions, transversions, specific codon site positions, or specific protein-coding regions. These graphical comparisons indicated that unpartitioned cytochrome b has evolved at 5–10 times the rate of scnDNA. Third-position transversions appeared to offer the most useful sequence partition for phylogenetic analysis because of their relatively fast rate of substitution (two times that of scnDNA) and negligible saturation. We also examined lineage-based rates of evolution by comparing branch length patterns between the nuclear and cytochrome b trees. The degree of correlation in corresponding branch lengths between cytochrome b and DNA hybridization trees depended on DNA sequence partitioning. When cytochrome b sequences were not partitioned, branch lengths in the cytochrome b and DNA hybridization trees were not correlated. However, when cytochrome b sequences were reduced to third-position transversions (i.e., unsaturated, relatively fast changing data), branch lengths were correlated. This finding suggests that lineage-based rates of DNA evolution in nuclear and mitochondrial genomes are influenced by common causes.
Interferon (IFN) induction followed by prolonged high dose IFN in combination with ribavirin (RBV) for relapser HCV patients: a randomized controlled multicenter trial
Authors: G. Fattovich, I. Zagni, G. Fomaciari, E. Minola, P. Fabris, S. Boccia, M. Giusti, G. Abbati, M. Felder, P. Rovere, A. Redaelli, A. Tonon, M. Montanari, C. Paternoster, E. Buscarini, E. Castagnetti, G. Tositti, C. Rizzo, S. Suppressa, M. Pantalena, F. Fa
Journal: Journal of Hepatology (2001)
Interferon-stimulated gene 15: a dual activity during hepatitis C virus infection
Authors: E. Estrabaud, T. Asselah
Journal: Gut (2010)

<h3>Background</h3> Mechanically ventilated patients in the intensive care unit (ICU) are unable to communicate verbally. We sought to evaluate their needs via a communication board (CB) and a novel eye tracking device (ETD) that verbalizes selections made by gazing. <h3>Methods</h3> This was a pilot prospective study conducted in a tertiary care surgical ICU. Continuously mechanically ventilated adult surgical ICU patients with a Richmond Agitation-Sedation Scale score of −1 to +1, without cognitive impairment, were eligible. We asked patients four yes-or-no questions to assess basic needs regarding presence of pain, need for endotracheal suction, satisfactory room temperature, and position comfort. Patients were then asked if there was anything else that they wanted to communicate. All responses were confirmed by head nodding. <h3>Results</h3> The median accuracy of the CB (100% (IQR 100%–100%)) for basic needs communication (yes/no questions) was comparable with that of the ETD (100% (IQR 68.8%–100%); p=0.14) in the 12 enrolled patients. Notably, 83% of patients desired to communicate additional information, ranging from spiritual (eg, desire for prayer/chaplain), emotional (eg, frustration, desire for comfort), physical/environmental (eg, television), to physiological (eg, thirst/hunger) needs. <h3>Discussion</h3> The majority of patients desired to communicate something other than basic needs. Unless specifically assessed via an assistive communication device (eg, CB or ETD), some of these other needs would have been difficult to discern. <h3>Level of evidence</h3> IV therapeutic care/management.
France approves exceptional embryo screening
Authors: A Dorozynski
Journal: BMJ (1994)

The French National Assembly has provoked controversy among doctors by ruling that genetic screening of reimplantation embryos should be authorised in exceptional cases. The ruling amends an earlier vote by the French Senate for a total ban on the technique. Some doctors fear that it may be a first step towards eugenics and have taken full page newspaper advertisements to publicise their …
The Neural Substrates of Affective Processing in Depressed Patients Treated With Venlafaxine
Authors: Richard J. Davidson, William Irwin, Michael J. Anderle, Ned H. Kalin
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated. METHOD: Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions. RESULTS: Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response. CONCLUSIONS: The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
Estimation of coronary risk factors in British schoolchildren: a preliminary report.
Authors: N Armstrong, J Balding, P Gentle, B Kirby
Journal: British Journal of Sports Medicine (1990)

Surveys from several countries have identified the presence of risk factors known to be associated with coronary heart disease in children. Data on the distribution of coronary risk factor variables in British children are scarce. This study was therefore designed to test the feasibility of collecting coronary risk factor data from British children and to conduct a preliminary examination of the problem. One hundred and seven children (mean age 12.8 yr) had their height, weight, triceps skinfold and blood pressure checked. Blood samples for cholesterol and HDL-cholesterol analysis were obtained from 93 children. Peak VO2 was determined on 48 children, 76 children had their daily activity monitored and 59 children's stage of sexual maturity was assessed. The boys' peak VO2 was significantly higher than the girls, whether expressed in l.min-1 (p less than 0.05) or ml.kg.-1min-1 (p less than 0.01). No other significant differences (p greater than 0.05) between the sexes were detected. The results indicate that children have relatively high serum cholesterol levels (boys 4.58 +/- 0.79; girls 4.72 +/- 0.80 mmol.l-1). The willingness and enthusiasm of the children, parents and schools to take part in the study clearly demonstrated the feasibility of a large scale study being successfully pursued in the United Kingdom.
Transient Sunitinib-Induced Coma in a Patient With Fibromyxoid Sarcoma
Authors: Laurent Arnaud, Noël E.C. Schartz, Guilhem Bousquet, Farid Sarandi, Olivier Verola, Isabelle Madelaine, Delphine Kerob, Céleste Lebbe
Journal: Journal of Clinical Oncology (2008)
Functional changes in acid secretion produced by duodenogastric reflux.
Authors: W E Thomas
Journal: Gut (1980)

The effects of duodenal reflux on gastric secretion have been examined in dogs. Acid secretion during pentagastrin stimulation increased by 68% in animals with chronic diversion of duodenal contents into the stomach. This increased acid secretion did not occur when bile alone was diverted into the stomach and could be abolished by vagotomy. The hypersecretion observed with pentagastrin did not occur when histamine was the stimulus, which suggests that it was not due solely to a trophic effect on parietal cells.
Influence of Cardiopulmonary Resuscitation Prior to Defibrillation in Patients With Out-of-Hospital Ventricular Fibrillation
Authors: Leonard A. Cobb
Journal: JAMA (1999)

Use of automated external defibrillators (AEDs) by first arriving emergency medical technicians (EMTs) is advocated to improve the outcome for out-of-hospital ventricular fibrillation (VF). However, adding AEDs to the emergency medical system in Seattle, Wash, did not improve survival. Studies in animals have shown improved outcomes when cardiopulmonary resuscitation (CPR) was administered prior to an initial shock for VF of several minutes' duration.To evaluate the effects of providing 90 seconds of CPR to persons with out-of-hospital VF prior to delivery of a shock by first-arriving EMTs.Observational, prospectively defined, population-based study with 42 months of preintervention analysis (July 1, 1990-December 31, 1993) and 36 months of post-intervention analysis (January 1, 1994-December 31, 1996).Seattle fire department-based, 2-tiered emergency medical system.A total of 639 patients treated for out-of-hospital VF before the intervention and 478 after the intervention.Modification of the protocol for use of AEDs, emphasizing approximately 90 seconds of CPR prior to delivery of a shock.Survival and neurologic status at hospital discharge determined by retrospective chart review as a function of early (<4 minutes) and later (> or =4 minutes) response intervals.Survival improved from 24% (155/639) to 30% (142/478) (P=.04). That benefit was predominantly in patients for whom the initial response interval was 4 minutes or longer (survival, 17% [56/321] before vs 27% [60/220] after; P = .01). In a multivariate logistic model, adjusting for differences in patient and resuscitation factors between the periods, the protocol intervention was estimated to improve survival significantly (odds ratio, 1.42; 95% confidence interval, 1.07-1.90; P = .02). Overall, the proportion of victims who survived with favorable neurologic recovery increased from 17% (106/634) to 23% (109/474) (P = .01). Among survivors, the proportion having favorable neurologic function at hospital discharge increased from 71% (106/150) to 79% (109/138) (P<.11).The routine provision of approximately 90 seconds of CPR prior to use of AED was associated with increased survival when response intervals were 4 minutes or longer.
SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis
Authors: Berna Uygur, Wen-Shu Wu
Journal: Molecular Cancer (2011)

SLUG is a zinc-finger transcription factor of the Snail/Slug zinc-finger family that plays a role in migration and invasion of tumor cells. Mechanisms by which SLUG promotes migration and invasion in prostate cancers remain elusive. Expression level of CXCR4 and CXCL12 was examined by Western blot, RT-PCR, and qPCR analyses. Forced expression of SLUG was mediated by retroviruses, and SLUG and CXCL12 was downregulated by shRNAs-expressing lentiviruses. Migration and invasion of prostate cancer were measured by scratch-wound assay and invasion assay, respectively. We demonstrated that forced expression of SLUG elevated CXCR4 and CXCL12 expression in human prostate cancer cell lines PC3, DU145, 22RV1, and LNCaP; conversely, reduced expression of SLUG by shRNA downregulated CXCR4 and CXCL12 expression at RNA and protein levels in prostate cancer cells. Furthermore, ectopic expression of SLUG increased MMP9 expression and activity in PC3, 22RV1, and DU-145 cells, and SLUG knockdown by shRNA downregulated MMP9 expression. We showed that CXCL12 is required for SLUG-mediated MMP9 expression in prostate cancer cells. Moreover, we found that migration and invasion of prostate cancer cells was increased by ectopic expression of SLUG and decreased by SLUG knockdown. Notably, knockdown of CXCL12 by shRNA impaired SLUG-mediated migration and invasion in prostate cancer cells. Lastly, our data suggest that CXCL12 and SLUG regulate migration and invasion of prostate cancer cells independent of cell growth. We provide the first compelling evidence that upregulation of autocrine CXCL12 is a major mechanism underlying SLUG-mediated migration and invasion of prostate cancer cells. Our findings suggest that CXCL12 is a therapeutic target for prostate cancer metastasis.
Forced vital capacity, airway obstruction and survival in a general population sample from the USA
Authors: P. G. J. Burney, R. Hooper
Journal: Thorax (2010)

<h3>Background</h3> Many studies show a link between forced expiratory volume in 1 s (FEV<sub>1</sub>) and survival in the general population and this has been interpreted as a link between airway obstruction and survival. However, the observation that vital capacity is also associated with survival weakens this interpretation. <h3>Methods</h3> Data on spirometry and survival were taken from the Atherosclerosis Risk in Communities (ARIC) limited access dataset. Survival among 7489 participants with usable spirometry and complete data was regressed against measures of ventilatory function after controlling for many other factors likely to be associated with survival. <h3>Results</h3> Survival was strongly associated with forced vital capacity (FVC) after adjustment for FEV<sub>1</sub>, but not the other way round. The fully adjusted hazard ratio (HR) associated with high FVC was 0.90 in men (95% CI 0.80 to 1.00; p=0.049) and 0.82 in women (95% CI 0.70 to 0.95; p=0.01). This compares with 0.98 for FEV<sub>1</sub> in men (95% CI 0.90 to 1.07; p.0.72) and 1.01 in women (95% CI 0.89 to 1.15; p=0.84). There was no association between survival and airway obstruction as measured by the FEV<sub>1</sub>/FVC ratio. <h3>Conclusions</h3> FVC but not airway obstruction predicts survival in asymptomatic adults without chronic respiratory diagnoses or persistent respiratory symptoms. The association is not explained by age, anthropometry, smoking, income occupation or blood pressure. As FVC later in life, cardiovascular risk, type II diabetes mellitus and low-grade systemic inflammation are all associated with poor fetal growth, these other conditions may be partly responsible for the poor survival in those with low FVC.
Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12R 2 inhibition
Authors: M.-L. Toh, M. Kawashima, A. Hot, P. Miossec, P. Miossec
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have a systemic Th1 defect associated with inflammation. <h3>Objective</h3> To examine the hypothesis that interleukin 17 (IL-17) contributes to this defect. <h3>Methods</h3> IL-17 effects on Th1 markers were examined on T-bet and interferon γ (IFNγ) expression in peripheral blood mononuclear cells (PBMCs) from patients with RA or healthy controls (HC). Receptor specificities were determined by analysis of the Th1-specific IL-12 receptor β2 (IL-12Rβ2), Th17-specific IL-23R and the common IL-12Rβ1 chain expression. Effects of IL-17 or IFNγ on IL-6, IL-1, IL-8, matrix metalloproteinase-8 (MMP-8) were measured by real-time RT-PCR in RA synovial cells. <h3>Results</h3> RA PBMCs were less responsive to IL-12-induced IFNγ than HC PBMCs. IL-12 hyporesponsiveness was increased by IL-17 treatment associated with a selective reduction in IL-12Rβ2, but not IL-23R, IL-12Rβ1 or T-bet, which was reversed with IL-17R inhibition. IL-17 inhibited IL-12Rβ2 expression in developing Th1 cells. In RA synovial cells, IL-17 induced IL-6, IL-1, IL-8 and MMP-8, whereas IFNγ had minimal or inhibitory effects. <h3>Conclusion</h3> In RA, IL-12 hyporesponsiveness is associated with IL-17R-mediated downregulation of IL-12Rβ2 expression. IL-17 may reinforce Th17 lineage commitment and proinflammatory and destructive effects through Th1 inhibition and positive feedback effects in RA synovial cells. Anti-inflammatory effects of IL-17/IL-17R antagonism may include the restoration of protective Th1 responses.
The evidentiary standard of special design is a little bit like heaven
Authors: Mark Schaller
Journal: Behavioral and Brain Sciences (2002)

Adaptationist explanations for well-known phenomena are of limited value to psychological science. To be truly useful, evolutionary psychological research programs must produce novel discoveries about contemporary cognitive and behavioral processes. The concept of special design is especially useful. Even if special design cannot be convincingly demonstrated, rigorous attempts to meet this evidentiary standard can produce novel scientific contributions.
Cathepsin B gene polymorphism Val26 is not associated with idiopathic chronic pancreatitis in European patients
Authors: F U Weiss, C-O Behn, P Simon, M Ruthenburger, W Halangk, M M Lerch
Journal: Gut (2007)

Pancreatitis is thought to be a disease of autodigestion triggered by premature and intracellular activation of digestive proteases.1 We and others have shown that lysosomal cathepsin B can activate trypsinogen intracellularly2 and that a large proportion of pancreatic cathepsin B is physiologically sorted into the secretory compartment.3 Further support for a role of cathepsin B in pancreatitis came from a recent study published by Mahurkar and coworkers in Gut 4 in which the authors reported that a leucine to valine mutation at position 26 of cathepsin B (L26V) is associated with tropical calcifying pancreatitis (odds ratio ∼2.2) in patients from southern India. Tropical calcifying pancreatitis is also associated (in up to 50% of cases) with mutations in the SPINK1 gene5—with N34S being the most common mutation. In the study by Mahurkar et al the cathepsin B L26V …
Hypoxia-Inducible Factor-2α Activation Promotes Colorectal Cancer Progression by Dysregulating Iron Homeostasis
Authors: Xiang Xue, Matthew Taylor, Erik Anderson, Cathy Hao, Aijuan Qu, Joel K. Greenson, Ellen M. Zimmermann, Frank J. Gonzalez, Yatrik M. Shah
Journal: Cancer Research (2012)

Abstract Hypoxia-inducible factor (HIF), a key modulator of the transcriptional response to hypoxia, is increased in colon cancer. However, the role of HIF in colon carcinogenesis in vivo remains unclear. In this study, we found that intestinal epithelium-specific disruption of the von Hippel–Lindau tumor suppressor protein (VHL) resulted in constitutive HIF signaling, and increased HIF expression augmented colon tumorigenesis in the Apcmin/+ intestinal tumor model. Intestine-specific disruption of Vhl increased colon tumor multiplicity and progression from adenomas to carcinomas. These effects were ameliorated in mice with double disruption of Vhl and HIF-2α. Activation of HIF signaling resulted in increased cell survival in normal colon tissue; however, tumor apoptosis was not affected. Interestingly, a robust activation of cyclin D1 was observed in tumors of Apcmin/+ mice in which HIF-2α was activated in the intestine. Consistent with this result, bromodeoxyuridine incorporation indicated that cellular proliferation was increased in colon tumors following HIF activation. Further analysis showed that dysregulation of the intestinal iron absorption transporter divalent metal transporter-1 (DMT-1) was a critical event in HIF-2α–mediated colon carcinogenesis. These data provide a mechanistic basis for the widely reported link between iron accumulation and colon cancer risk. Together, our findings show that a chronic increase in HIF-2α in the colon initiates protumorigenic signaling, which may have important implications in developing preventive and therapeutic strategies for colon cancer. Cancer Res; 72(9); 2285–93. ©2012 AACR.