tbuckley/cabot-search huggingface dataset:
Non–Small-Cell Lung Cancer mRNA Expression Signature Predicting Response to Adjuvant Chemotherapy
Authors: Yang Xie, John D. Minna
Journal: Journal of Clinical Oncology (2010)

98% of those with localized disease and 84% of those with spread to regional lymph nodes.Even for those diagnosed in the early 1980s, more than half are alive 20 years later. 19Clearly, women with breast cancer are living long enough to be vulnerable to death as a result of cardiovascular disease, which is still the number one cause of death among US women. 20In addition, there is some evidence that breast cancer treatments may increase the risk of cardiovascular disease or its antecedents.The risk of metabolic disease may be increased by treatment-induced estrogen deficiency, 21 and radiation may cause direct damage to the myocardium and coronary arteries. 22he study by Kwan et al 1 is important because it elucidates a mystery in the literature concerning lifestyle factors that affect breast cancer survival.Their data showed the expected decrease in survival when recurrence and breast cancer death were used as end points, and no decrease in overall survival with alcohol intake.Of interest, the cut point of Ͻ 6.0 and Ն 6.0 g/d used in the Kwan et al study falls squarely in the range of 5.0 to 14.9 g/d, which represented the optimum balance between increased breast cancer mortality and decreased cardiovascular mortality among initially healthy women in the Fuchs et al study. 18The fact that most previous studies of alcohol and breast cancer survival used total mortality as the end point explains the previous null results.The study by Kwan et al 1 is also important because it gives guidance to women living with breast cancer and their clinicians.Their decision is the same as that facing women without breast cancer; the answer is not a clear-cut yes or no.Moderate consumption of alcohol is likely to increase a woman's risk of dying as a result of breast cancer while decreasing her risk of dying as a result of heart disease.Whether to consume alcohol is an individual decision and is dependent on each woman's evaluation of and comfort level with those risks.
Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time
Authors: Mariella G. Filbin, Mario L. Suvà
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Gliomas are the most common primary human brain tumors and occur in both adults and children. Over the past few years, systematic large-scale genomic and epigenomic profiling has provided unprecedented insight into their pathogenesis, uncovering alterations in an unanticipated number of genes and regulatory elements. In this review, we discuss recent discoveries about the genomics and epigenomics of adult and pediatric gliomas and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to glioma development, offer insight into the cancer stem cell model, help refine classifications, and should lay the foundation for improved clinical care.
Criteria and evaluation of cognitive theories
Authors: Petros A. M. Gelepithis
Journal: Behavioral and Brain Sciences (2003)

I have three types of interrelated comments. First, on the choice of the proposed criteria, I argue against any list and for a system of criteria. Second, on grading, I suggest modifications with respect to consciousness and development. Finally, on the choice of “theories” for evaluation, I argue for Edelman's theory of neuronal group selection instead of connectionism (classical or not).
A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3
Authors: Jean‐Louis Delaunay, Anne‐Marie Durand‐Schneider, Claire Dossier, Thomas Falguières, Julien Gautherot, Anne Davit‐Spraul, Tounsia Aït‐Slimane, Chantal Housset, Emmanuel Jacquemin, Michèle Maurice
Journal: Hepatology (2015)

Progressive familial intrahepatic cholestasis type 3 is caused by biallelic variations of ABCB4, most often (≥70%) missense. In this study, we examined the effects of 12 missense variations identified in progressive familial intrahepatic cholestasis type 3 patients. We classified these variations on the basis of the defects thus identified and explored potential rescue of trafficking‐defective mutants by pharmacological means. Variations were reproduced in the ABCB4 complementary DNA and the mutants, thus obtained, expressed in HepG2 and HEK293 cells. Three mutants were either fully (I541F and L556R) or largely (Q855L) retained in the endoplasmic reticulum, in an immature form. Rescue of the defect, i.e., increase in the mature form at the bile canaliculi, was obtained by cell treatments with cyclosporin A or C and, to a lesser extent, B, D, or H. Five mutations with little or no effect on ABCB4 expression at the bile canaliculi caused a decrease (F357L, T775M, and G954S) or almost absence (S346I and P726L) of phosphatidylcholine secretion. Two mutants (T424A and N510S) were normally processed and expressed at the bile canaliculi, but their stability was reduced. We found no defect of the T175A mutant or of R652G, previously described as a polymorphism. In patients, the most severe phenotypes appreciated by the duration of transplant‐free survival were caused by ABCB4 variants that were markedly retained in the endoplasmic reticulum and expressed in a homozygous status. Conclusion: ABCB4 variations can be classified as follows: nonsense variations (I) and, on the basis of current findings, missense variations that primarily affect the maturation (II), activity (III), or stability (IV) of the protein or have no detectable effect (V); this classification provides a strong basis for the development of genotype‐based therapies. (H epatology 2016;63:1620‐1631)
Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1
Authors: J.-J. Yim
Journal: Thorax (2000)

Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD.The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers.No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group.Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.
Specific alpha 1-adrenergic receptor subtypes modulate catecholamine-induced increases and decreases in ventricular automaticity.
Authors: U del Balzo, M R Rosen, G Malfatto, L M Kaplan, S F Steinberg
Journal: Circulation Research (1990)

Fifty percent of adult canine Purkinje fibers manifest a decrease in automaticity in response to alpha 1-adrenergic stimulation with 10(-10)-10(-8) M norepinephrine (NE), and 50% manifest an increase. In contrast, most neonatal Purkinje fibers show an increase in automaticity in response to these concentrations of NE. We studied the modulation of NE effects, using the subtype selective alpha 1-adrenergic antagonists chloroethylclonidine (CEC) and WB 4101. CEC selectively antagonized the decrease in automatically such that, in both age groups, all Purkinje fibers showed NE-induced increases in automaticity. In Purkinje fibers from dogs treated with pertussis toxin, NE no longer induced a CEC-sensitive decrease in automaticity. In contrast, WB 4101 selectively antagonized the NE-induced increase in automaticity in both age groups. In the presence of WB 4101, NE decreased automaticity uniformly in adult Purkinje fibers and tended to induce no change in automaticity in neonatal Purkinje fibers. In the presence of prazosin (10(-6) M) or combined CEC (10(-7) M) and WB 4101 (10(-7) M), no alpha-agonist-induced increase or decrease in rate was observed. Pretreatment of membranes from newborn and adult dog and rat ventricles with CEC resulted in a selective and irreversible inactivation of 25% of specific binding sites labeled with [125I]IBE2254. In cultured neonatal rat ventricular myocytes, exposure to CEC resulted in a 35% decrease in the density of specific binding sites labeled with [125I]IBE2254 but did not influence alpha-adrenergic stimulation of inositol phosphate accumulation. In contrast, WB 4101 inactivated NE-stimulated inositol phosphate accumulation. Our results suggest that 1) at least two distinct alpha 1-adrenergic receptor subtypes are present in neonatal and adult cardiac tissue, 2) the CEC-sensitive subtype is linked to a decrease in automaticity via a pertussis toxin-sensitive substrate, 3) the WB 4101-sensitive subtype is linked to an increase in automaticity (possibly via a mechanism related to phosphoinositide breakdown), and 4) although CEC- and WB 4101-sensitive alpha 1-adrenergic receptor subtypes are present in the neonate, only the WB 4101-sensitive subtype is expressed functionally to induce effects on ventricular automaticity.
Sympathetic Vasomotor Response of the Radial Artery in Patients With Diabetic Foot Syndrome
Authors: Bernhard M. Eicke, Julian Bauer, Susanne Mink, Valerio Kuhl, Alexander Hlawatsch, Ernst Küstner, Anja Victor
Journal: Diabetes Care (2003)

Neurophysiological assessment of the peripheral autonomic system is characterized by various limitations. An alternative approach to laser Doppler and venous plethymography is the assessment of the sympathetic vasomotor response of the radial artery obtained by continuous wave Doppler sonography. Nomogram data have been established and demonstrate the temporary disappearance of diastolic flow after coughing or deep inspiration.We assessed the sympathetic vasomotor response in 25 patients (mean age 64 years, range 43-76) with diabetic foot syndrome. The Doppler data were correlated with nerve conduction studies of the median and peroneal nerve, the extent of radiologically diagnosed media sclerosis, and compared with nomogram values (n = 41).Although similar mean flow velocities were found under baseline conditions, the flow pattern was characterized by higher pulsatility in the diabetic group (resistance index [RI] 1.1 vs. 0.7). No significant difference in RI was observed after coughing. The latency of onset of the response was prolonged (2.1 vs. 1.5 s), while the duration of the response did not differ (18 vs. 15 s). Only the nerve conduction velocity of the peroneal nerve correlated inversely with the RI. The extent of radiologically proven calcification tended to correlate with the pulsatility of the baseline signal and the response latencies.The data obtained by this study suggest the concurrent existence of reduced vessel elasticity due to media sclerosis and dysfunction of the autonomic vasomotor system.
Upper airway {middle dot} 2: Bronchiectasis, cystic fibrosis and sinusitis
Authors: M R Loebinger, D Bilton, R Wilson
Journal: Thorax (2009)

The nose and paranasal sinuses are contiguous with the lower respiratory tract. Patients with bronchiectasis and cystic fibrosis commonly have sinonasal disease, which is thought to have the same aetiology and pathophysiology as the chronic lung disease. Despite this, the conditions are rarely considered together and there is very little literature on the treatment of sinonasal disease in bronchiectasis. In addition to being a common cause of comorbidity, there is evidence suggesting that sinonasal disease may directly influence the bronchial condition. This article reviews sinonasal disease in bronchiectasis and cystic fibrosis and addresses the possible interactions between the health and disease of the upper and lower airways.
Patients with ACTN4 Mutations Demonstrate Distinctive Features of Glomerular Injury
Authors: Joel M. Henderson, Mariam P. Alexander, Martin R. Pollak
Journal: Journal of the American Society of Nephrology (2009)

Mutations in ACTN4, the gene encoding the actin-binding protein alpha-actinin-4, are a cause of familial FSGS. We examined kidney biopsies from patients with ACTN4 mutations to characterize systematically the histopathology of kidney damage in these patients and to determine whether distinctive morphologic changes are associated with mutations in this gene. The changes observed with light microscopy were typical of FSGS and were morphologically heterogeneous, similar to other inherited podocytopathies. The ultrastructural characteristics, however, were distinctive: Most notably, the presence of cytoplasmic electron-dense aggregates in podocytes. Indirect immunofluorescence using antibodies to a conserved domain of alpha-actinin-4 (present in both wild-type and mutant proteins) revealed a segmental and irregular granular staining pattern in the capillary walls of preserved glomeruli of ACTN4 mutants, whereas preserved glomeruli of patients with other podocyte diseases retained a global linear staining pattern for alpha-actinin-4. These characteristics resemble features observed in mouse models of this disease and may aid in the identification of patients and families who harbor ACTN4 mutations.
Platin or No Platin? That Is the Question
Authors: Joan H. Schiller
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.76.018 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12837812 Platin or No Platin? That Is the Question Joan H. SchillerxJoan H. SchillerSearch for articles by this author Show More Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison, WI https://doi.org/10.1200/JCO.2003.76.018 Full Text PDF Figures and Tables "Platin or No Platin? That Is the Question." Journal of Clinical Oncology, 21(16), pp. 3009–3010© 2003 by American Society of Clinical Oncology
Effects of long wave ultraviolet radiation on photosensitizing and related compounds. I
Authors: MILHIM D. ALANI
Journal: British Journal of Dermatology (2006)

The effects of long ultraviolet radiation (UVA) on the fluorescence of twenty-four photosensitizing and related compounds were studied. Each compound was applied in two areas on the skin of hairless mice. One area was irradiated. The fluorescence in both areas was then inspected every day until it disappeared. Persistence and change of colour of the fluorescence as a direct immediate effect of UVA radiation on compounds having photoallergic potential, i.e. salicylanilide, halogenated salicylanilide and phenothiazine derivatives, was observed. Compounds known for their phototoxic effects, i.e. acridine dyes, did not show such changes after irradiation, while 8-methoxypsoralen showed persistence of fluorescence without change of colour.
Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process
Authors: Santos A. Susin, Hans K. Lorenzo, Naoufal Zamzami, Isabel Marzo, Catherine Brenner, Nathanael Larochette, Marie-Christine Prévost, Pedro M. Alzari, Guido Kroemer
Journal: The Journal of Experimental Medicine (1999)

The barrier function of mitochondrial membranes is perturbed early during the apoptotic process. Here we show that the mitochondria contain a caspase-like enzymatic activity cleaving the caspase substrate Z-VAD.afc, in addition to three biological activities previously suggested to participate in the apoptotic process: (a) cytochrome c; (b) an apoptosis-inducing factor (AIF) which causes isolated nuclei to undergo apoptosis in vitro; and (c) a DNAse activity. All of these factors, which are biochemically distinct, are released upon opening of the permeability transition (PT) pore in a coordinate, Bcl-2-inhibitable fashion. Caspase inhibitors fully neutralize the Z-VAD.afc-cleaving activity, have a limited effect on the AIF activity, and have no effect at all on the DNase activities. Purification of proteins reacting with the biotinylated caspase substrate Z-VAD, immunodetection, and immunodepletion experiments reveal the presence of procaspase-2 and -9 in mitochondria. Upon induction of PT pore opening, these procaspases are released from purified mitochondria and become activated. Similarly, upon induction of apoptosis, both procaspases redistribute from the mitochondrion to the cytosol and are processed to generate enzymatically active caspases. This redistribution is inhibited by Bcl-2. Recombinant caspase-2 and -9 suffice to provoke full-blown apoptosis upon microinjection into cells. Altogether, these data suggest that caspase-2 and -9 zymogens are essentially localized in mitochondria and that the disruption of the outer mitochondrial membrane occurring early during apoptosis may be critical for their subcellular redistribution and activation.
A Central Role for Tumor-derived Monocyte Chemoattractant Protein-1 in Malignant Pleural Effusion
Authors: G. T. Stathopoulos, I. Psallidas, A. Moustaki, C. Moschos, A. Kollintza, S. Karabela, I. Porfyridis, S. Vassiliou, M. Karatza, Z. Zhou, M. Joo, T. S. Blackwell, C. Roussos, D. Graf, I. Kalomenidis
Journal: JNCI Journal of the National Cancer Institute (2008)

Tumor cells in malignant pleural effusions (MPEs) are an important source of monocyte chemoattractant protein (MCP)-1. However, the role of tumor-derived MCP-1 in the pathogenesis and progression of MPE has not been determined. B16 mouse skin melanoma cells, which are deficient in MCP-1 expression, and mouse Lewis lung cancer (LLC) cells, which express high levels of MCP-1, were engineered to stably express MCP-1 and short hairpin RNAs (shRNAs) targeting the MCP-1 transcript, respectively. Cells were injected into the pleural cavities of syngeneic immunocompetent mice, and MPE volume and pleural tumors were quantified at necropsy (day 14). MCP-1 and other mediators were determined by cytometric bead array and enzyme-linked immunosorbent assay, and mononuclear and endothelial cells were identified by immunolabeling of F4/80 and factor VIII–related antigen respectively. Mouse survival was assessed using Kaplan–Meier analysis. Vascular permeability in mice with MPE was assessed using albumin-binding Evans blue. Statistical tests were two-sided. LLC cells expressing shRNA against MCP-1 elaborated less than 5% of the MCP-1 level in cells expressing nonspecific shRNA (control cells), and intrapleural delivery of these cells resulted in less MPE (mean MPE volume = 86 and 585 μL, respectively; difference = 499 μL; 95% confidence interval [CI] = 331 to 669 μL; P < .001), reduced MCP-1 levels in the pleural fluid, and lower mortality than when control cells were delivered. Overexpression of MCP-1 in intrapleurally injected B16 melanoma cells led to increased MPE and reduced survival. In mice with MPE, MCP-1 was a potent inducer of vascular permeability, mononuclear recruitment, and, in pleural tumors, of angiogenesis. MCP-1 produced by tumor cells is an important determinant of their capacity to induce the formation of MPE and may be a useful target for the treatment of malignant pleural disease.
Angiotensin-converting enzyme inhibitor-induced renal failure
Authors: D E Hricik, M J Dunn
Journal: Journal of the American Society of Nephrology (1990)

Angiotensin-converting enzyme inhibitor-induced renal failure is now a well-recognized phenomenon that appears to occur almost exclusively in patients with a preexisting reduction in renal perfusion pressure, especially those with renovascular disease. In the latter group of patients, renal failure probably results from some combination of reduced poststenotic renal perfusion pressure and a unique disturbance in the autoregulation of glomerular filtration rate. Although traditionally regarded as functional and reversible, recent animal studies suggest that angiotensin-converting enzyme inhibitor-induced reductions of glomerular filtration rate may lead to progressive renal atrophy, an observation that raises concerns about the long-term safety of these agents in patients with renovascular disease. On the other hand, the deleterious consequences of angiotensin-converting enzyme inhibition in renovascular disease have been exploited as aids in the diagnosis of this disorder. Whether the adjunctive use of angiotensin-converting enzyme inhibitors will prove to be useful in screening large populations of hypertensive patients for renovascular hypertension remains to be determined. However, such adjunctive tests appear to be useful in judging the functional significance of angiographically documented renal artery stenosis.
Mental models and pragmatics
Authors: P. N. Johnson-Laird, Ruth M. J. Byrne
Journal: Behavioral and Brain Sciences (2000)

Van der Henst argues that the theory of mental models lacks a pragmatic component. He fills the gap with the notion that reasoners draw the most relevant conclusions. We agree, but argue that theories need an element of “nondeterminism.” It is often impossible to predict either what will be most relevant or which particular conclusion an individual will draw.
Evolution of the Gypsy Endogenous Retrovirus in the Drosophila melanogaster Subgroup
Authors: C Terzian, C Ferraz, J Demaille, A Bucheton
Journal: Molecular Biology and Evolution (2000)

We conducted a phylogenetic survey of the endogenous retrovirus Gypsy in the eight species of the Drosophila melanogaster subgroup. A 362-bp fragment from the integrase gene (int) was amplified, cloned, and sequenced. Phylogenetic relationships of the elements isolated from independent clones were compared with the host phylogeny. Our results indicate that two main lineages of Gypsy exist in the melanogaster subgroup and that vertical and horizontal transmission have played a crucial role in the evolution of this insect endogenous retrovirus.
Injury surveillance during the 2010 IRB Women's Rugby World Cup
Authors: Aileen E Taylor, Colin W Fuller, Michael G Molloy
Journal: British Journal of Sports Medicine (2011)

Objective To assess and evaluate injuries sustained during the 2010 Women's Rugby World Cup. Design Prospective, cohort. Participants 285 women rugby players. Results Incidence of match injury was 35.5/1000 player-hours; mean severity was 55.0 days and median severity 9 days. Only one training injury was reported. Knee-ligament injuries were the most common (15%) and resulted in most days lost (43%). The tackle was the cause of most injuries. Conclusions The risk of injury in international rugby is significantly lower for women than for men. Further research is required to assess knee-ligament injuries in women's rugby.