tbuckley/cabot-search huggingface dataset:
Novel Nox inhibitor VAS2870 attenuates PDGF-dependent smooth muscle cell chemotaxis, but not proliferation☆
Authors: H TENFREYHAUS, M HUNTGEBURTH, K WINGLER, J SCHNITKER, A BAUMER, M VANTLER, M BEKHITE, M WARTENBERG, H SAUER, S ROSENKRANZ
Journal: Cardiovascular Research (2006)

Reactive oxygen species (ROS) produced by NAD(P)H oxidases (Nox) play a significant role in the pathophysiology of cardiovascular diseases. Expression and activity of NAD(P)H oxidases are regulated by growth factors such as angiotensin II and platelet-derived growth factor (PDGF). We characterized the effects of the novel Nox inhibitor VAS2870 on PDGF-dependent ROS liberation and cellular events in vascular smooth muscle cells (VSMC).PDGF-BB increased NAD(P)H oxidase activity (lucigenin-enhanced chemiluminescence) and intracellular ROS levels (detected by confocal laserscanning microscopy using 2,7-DCF) to 229+/-9% and 362+/-54% at 1 and 2 h, respectively. Preincubation with VAS2870 (10 and 20 microM) completely abolished PDGF-mediated NAD(P)H oxidase activation and ROS production. Since ROS are involved in various growth factor-induced cellular functions, the influence of VAS2870 on PDGF-induced DNA synthesis and chemotaxis was determined. PDGF promoted a 4.2+/-0.2-fold increase of VSMC migration (modified Boyden chamber, p<0.01) and increased DNA synthesis by maximally 3.2+/-0.4-fold (BrdU incorporation, p<0.01) in a concentration-dependent manner. Preincubation with VAS2870 (0.1-20 microM) did not affect PDGF-induced cell cycle progression. However, it abolished PDGF-dependent chemotaxis of VSMC in a concentration-dependent manner (100% inhibition at 10 microM). These findings were related to PDGF-dependent signaling events. Western blot analyses using phospho-specific antibodies revealed that the downstream signaling molecules Akt, Erk, and Src were activated by PDGF. However, VAS2870 blocked PDGF-dependent activation of Src, but not of Akt and Erk, in a concentration-dependent manner.VAS2870 effectively suppresses growth factor-mediated ROS liberation in VSMC. Furthermore, it completely inhibits PDGF-dependent VSMC migration, whereas it does not affect DNA synthesis. These divergent effects reflect the critical role of Src activity, which-in contrast to Akt and Erk-appears to be redox-sensitive and is absolutely required for PDGF-induced chemotaxis, but not cell cycle progression.
Biochemical characteristics of isolated rat liver stellate cells
Authors: Masao Yamada, William S. Blaner, Dianne Robert Soprano, Joseph L. Dixon, Hild M. Kjeldbye, Dewitt S. Goodman
Journal: Hepatology (1987)

Hepatic stellate cells play a quantitatively important role in hepatic retinoid metabolism and storage in rats maintained under normal nutritional conditions. Studies were conducted to further explore the biochemical characteristics of hepatic stellate cells. Stellate cells were isolated in high purity and yield from the livers of normal rats. The isolated cells had the morphology expected (on electron micrographs) for stellate cells, and were enriched in retinoids and in the intracellular retinoid-binding proteins. The composition of the stellate cell lipid droplets was examined. These lipid droplets were isolated in high purity and integrity from frozen and thawed stellate cell preparations by differential centrifugation. We estimate that the lipid composition of stellate cell lipid droplets consisted of approximately 42% retinyl ester, 28% triglyceride, 13% cholesterol (total) and 4% phospholipid. Thus, stellate cell lipid droplets contain substantial levels of both cholesterol and triglyceride, in addition to retinyl esters. Stellate cell homogenates were assayed for both retinol-binding protein and transthyretin by specific radioimmunoassays. Within the detection limits of these radioimmunoassays, we were unable to detect the presence of either retinol-binding protein (&lt;9 ng per 10 6 cells) or transthyretin (&lt;11 ng per 10 6 cells) in the stellate cell preparations. Total RNA, prepared from the isolated stellate cells, was examined by Northern blot analysis for retinol-binding protein mRNA and transthyretin mRNA, using cDNA probes for retinol-binding protein and transthyretin. Within the sensitivity of these assays, retinol-binding protein mRNA and transthyretin mRNA were not detected in stellate cells. These findings suggest that stellate cells do not synthesize or accumulate retinol-binding protein.
Old wine (most of it) in new bottles: Where are dreams and what is the memory?
Authors: Ramon Greenberg
Journal: Behavioral and Brain Sciences (2005)

I discuss how the work in Walker's article adds to the considerable body of research on dreaming, sleep, and memory that appeared in the early days of modern sleep research. I also consider the issue of REM-independent and REM-dependent kinds of learning. This requires including emotional issues in our discussion, and therefore emphasizes the importance of studying and understanding dreams.
Cerebral CT scan abnormalities in cholestatic and hepatocellular disease and their relationship to neuropsychologic test performance
Authors: Patricia Bernthal, Amy Hays, Ralph E. Tarter, David Van Thiel, James Lecky, Andrea Hegedus
Journal: Hepatology (1987)

Forty-nine nonalcoholic cirrhotic patients, on whom cranial CT scans were available, were administered a battery of neuropsychological tests. Although none of the subjects exhibited clinical signs or symptoms of hepatic encephalopathy, quantification of the CT scan image implicated cerebral edema and cortical atrophy. In addition numerous significant correlations were observed between the CT variables and neuropsychological test performance. The findings are conjectured to reflect previously unrecognized cerebral morphologic changes associated with chronic subclinical portal-systemic encephalopathy.
Akirins are highly conserved nuclear proteins required for NF-κB-dependent gene expression in drosophila and mice
Authors: Akira Goto, Kazufumi Matsushita, Viola Gesellchen, Laure El Chamy, David Kuttenkeuler, Osamu Takeuchi, Jules A Hoffmann, Shizuo Akira, Michael Boutros, Jean-Marc Reichhart
Journal: Nature Immunology (2007)
Wegener’s granulomatosis presenting as neutrophilic dermatosis: a case report
Authors: L. Gürses, D. Yücelten, A. Cömert, T. Ergun, O. Gürbüz
Journal: British Journal of Dermatology (2000)

Sir, Wegener’s granulomatosis (WG) is a distinct clinicopathological entity of unknown origin. The ‘classic’ clinicopathological triad consists of necrotizing granuloma of the upper and lower respiratory tract, focal necrotizing glomerulitis and generalized vasculitis of both small‐ to medium‐sized arteries and veins.1,2 However, not all patients with WG fulfil the triad; atypical presentations, limited and latent forms have been described more often in recent years.3 We report a WG patient with skin lesions presenting as neutrophilic dermatosis in whom granulomatous skin lesions developed later. A 67‐year‐old woman had a 1‐week history of painful skin lesions on the right foot and the face. She had been on treatment with calcium carbonate, erythropoietin and vitamin α‐D3 for chronic renal failure, during the previous 6 months. Examination revealed a haemorrhagic bullous plaque with an indurated base on the dorsum of the right foot (Fig. 1a) and a similar lesion with small blisters and pustules on the right cheek (Fig. 1b). An erythematous, slightly infiltrated plaque on the forehead and erythematous papular lesions on the dorsa of fingers were also observed. The differential diagnosis was pyoderma gangrenosum, Sweet syndrome or leukocytoclastic vasculitis. Histopathological examination of a biopsy from the right foot showed diffuse intersititial mixed inflammatory cell infiltrate rich in polymorphonuclear leucocytes, intense oedema of the upper dermis, leukocytoclasia and erythrocyte extravasation. A biopsy from the forehead revealed granulomatous infiltration with a few neutrophils and a single focus of nuclear dust with no other vasculitic changes.
Cost–Utility Analysis of Short- Versus Long-Course Palliative Radiotherapy in Patients With Non–Small-Cell Lung Cancer
Authors: Wilbert B. van den Hout, Gijsbert W. P. M. Kramer, Ed M. Noordijk, Jan-Willem H. Leer
Journal: JNCI Journal of the National Cancer Institute (2006)

Radiotherapy can effectively palliate the symptoms of poor-prognosis patients with non-small-cell lung cancer. However, controversy remains about whether short-course or more protracted radiotherapy schedules provide better value for the money. We conducted a societal cost-utility analysis of a Dutch multicenter randomized trial with 1-year follow-up that compared the efficacy of radiotherapy schedules consisting of 10 fractions of 3 Gy (10 x 3 Gy) versus two fractions of 8 Gy (2 x 8 Gy) in 297 patients with inoperable stage IIIA/B or stage IV non-small-cell lung cancer. this trial found that the 10 x 3-Gy group had better survival than the 2 x 8-Gy group.Lifetime quality-adjusted life-years (QALYs) were estimated using the EuroQol questionnaire. Lifetime societal costs were estimated using a model estimated based on data from cost questionnaires filled out by a subset of patients (n = 56). Differences were analyzed statistically using two-sided nonparametric bootstrapping.Compared with the 2 x 8-Gy group, the 10 x 3-Gy group accrued statistically significantly more QALYs (20.0 versus 13.2 weeks; difference = 6.8 weeks, 95% confidence interval [CI] = 0.1 to 13.5 weeks, P = .05), which was mainly due to the statistically significantly better survival (38.1 versus 27.4 weeks; difference = 10.7 weeks, 95% CI = 0.9 to 20.6 weeks, P = .03) without a statistically significant difference with respect to the average valuation of health (P = .27). Total radiotherapy and radiotherapy-related costs were estimated at 5236 dollars for the 10 x 3-Gy group and 2512 dollars for the 2 x 8-Gy group (difference = 2724 dollars, 95% CI = 2501 dollars to 2947 dollars, P<.001). The 39% increase in life expectancy in the 10 x 3-Gy group as compared with the 2 x 8-Gy group was associated with a 30% increase in survival-related nonradiotherapy costs (11,254 dollars versus 8651 dollars, difference 2602 dollars, 95% CI = -357 dollars to 5562 dollars, P = .09). The cost-utility ratio for the 10 x 3-Gy schedule versus the 2 x 8-Gy schedule was estimated at 40,900 dollars per QALY (95% CI = 19,400 dollars to 1,100,000 dollars per QALY).In these poor-prognosis non-small-cell lung cancer patients, the estimated cost-utility ratio for the palliative 10 x 3-Gy schedule was acceptable according to current economic standards. However, the additional costs for the protracted schedule were justified not by improved quality of life but by longer survival.
Surfactant Protein A and B Genetic Variants in Respiratory Distress Syndrome in Singletons and Twins
Authors: Riitta Marttila, Ritva Haataja, Susan Guttentag, Mikko Hallman
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in combination. SP-A1 allele 6A2 (p = 0.009) and the homozygous genotype 6A2/6A2 (p = 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p = 0.012 for 6A2 and p = 0.03 for 6A2/6A2) or Thr/Thr (p = 0.12 for 6A2 and p = 0.018 for 6A2/6A2, respectively). The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS.
ELECTRON MICROSCOPY OF SERUM SICKNESS NEPHRITIS
Authors: Joseph D. Feldman
Journal: The Journal of Experimental Medicine (1958)

The renal lesions of serum sickness were studied with the electron microscope. The most prominent change was a marked swelling and proliferation of glomernlar endothelial cells causing obliteration of the capillary lumen. The basement membrane also showed focal thickenings and excrescences. Deposits of electron-dense material blended into the basement membrane. On the extracapillary side epithelial foot processes were reduced in number and replaced by broad sheets of cytoplasm which were closely applied to the basement membrane. From a comparison of electron and fluorescent microscopic studies of the glomerulus in serum sickness, it would seem that antigen-antibody complexes initiated injury in endothelial cells, although the possibility of the primary reaction occurring on basement membrane cannot be excluded.
The involvement of T cell receptor peptide-specific regulatory CD4+ T cells in recovery from antigen-induced autoimmune disease.
Authors: V Kumar, E E Sercarz
Journal: The Journal of Experimental Medicine (1993)

Experimental allergic encephalomyelitis (EAE) is a prototype for CD4+ T cell-mediated autoimmune diseases. Immunization with myelin basic protein (MBP) in B10.PL mice results in EAE, and a majority of animals recover permanently from the disease. Most MBP-reactive encephalitogenic T cells recognize an immunodominant NH2-terminal peptide, Ac1-9, and predominantly use the T cell receptor (TCR) V beta 8.2 gene segment. Here we report that in mice recovering from MBP-induced EAE, peripheral T cells proliferate in response to a single immunodominant TCR peptide from the V beta 8.2 chain (amino acids 76-101), indicating natural priming during the course of the disease. Cloned T cells, specific for this TCR peptide, specifically downregulate proliferative responses to Ac1-9 in vivo and also protect mice from MBP-induced EAE. These regulatory T cells express CD4 molecules and recognize a dominant peptide from the TCR variable framework region of V beta 8.2, in the context of the major histocompatibility complex class II molecule, I-Au, and predominantly use the TCR V beta 14 gene segment. This is the first demonstration of the physiological induction of TCR peptide-specific CD4+ T cells that result from MBP immunization and that are revealed only during the recovery from disease. The downregulation of disease-causing T cells by TCR peptide-specific T cells offers a mechanism for antigen-specific, network-induced recovery from autoimmune disease.
An unlikely aphasiologist: D J Larrey (1766-1842)
Authors: E H Jellinek
Journal: Journal of the Royal Society of Medicine (2002)

The vast literature of aphasia is rich in improbabilities and guesses from false premises.Two pioneers have become eponyms (Broca and Wernicke), and many are famous, such as Gall, Bouillaud, Trousseau and Pierre Marie in France, Liepmann in Germany, and Hughlings Jackson and Bastian in England.Larrey too deserves fame, but was only cited by his contemporaries, Gall and Osborne.The nosography of aphasia 1-3 started with dramatic single case reports, centuries before Broca's watershed paper in 1861 on the site of aphasia in the left second and third frontal gyri.Some of the early accounts were by great writers, among them Samuel Johnson (of himself) 4 and Goethe (probably of his maternal grandfather) 1 ; and the Swedish botanist and physician Linnaeus wrote of the condition in a fellow academic at Uppsala 5 .Pinel, the Paris liberator of psychiatric patients, gave a classic description in 1809 of a notary who could not speak, read or write after a stroke 1 .But the writings of Larrey contain no fewer than twelve cases of aphasia, two with illustrations.This military surgeon started his long career in the navy of the Bourbons in 1787, and recorded his experiences in twenty-six bloody Napoleonic campaigns, and their aftermath, in two multivolume oeuvres-the chronological Me ´moires de Chirurgie Militaire et Campagnes 6 up to 1814 and Relation Me ´dicale de Campagnes . . .de 1815 a`1840 7 , and the more didactic Clinique Chirurgicale dans les Camps et Ho ˆpitaux Militaires 8 .
Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time
Authors: G S Alarcon
Journal: Annals of the Rheumatic Diseases (2006)

To ascertain the predictive factors of high levels of disease activity in systemic lupus erythematosus (SLE).Patients with SLE (American College of Radiology criteria), aged >or=16 years, with disease duration <or=5 years and of Hispanic (Texas and Puerto Rico), African American and Caucasian ethnicities, were included. The outcome was high disease activity at any time (Systemic Lupus Activity Measure-Revised >10). A basic multivariable model (including age, sex, ethnicity, health insurance, social support, abnormal illness-related behaviours, helplessness and prior disease activity) was first examined. Additional models were built by including other variables.554 patients (100 Hispanics from Texas, 94 Hispanics from Puerto Rico, 199 African Americans, 161 Caucasians) and 2366 visits were analysed; 47% of the patients and 29% of the visits met the definition of high disease activity (more common among African Americans (72.0%) and Hispanics from Texas (71.3%) than among Caucasians (43.9%) and Hispanics from Puerto Rico (31.9%)). Variables found to predict high levels of disease activity were Hispanic (from Texas) and African American ethnicities, lack of health insurance, helplessness, abnormal illness-related behaviours and poor social support; age was negatively associated with high levels of disease activity. African admixture and anti-double-stranded DNA antibodies also predicted high levels of disease activity, as did prior disease activity. None of the human leucocyte antigen variables were retained in the models.Socioeconomic-demographic (age, ethnicity, health insurance), behavioural and psychological variables are important mediators of high levels of disease activity in SLE during its course. Interventions aimed at modifiable factors may improve the outcomes of SLE.
Conditional Mutation of Pkd2 Causes Cystogenesis and Upregulates β-Catenin
Authors: Ingyu Kim, Tianbing Ding, Yulong Fu, Cunxi Li, Lan Cui, Ao Li, Peiwen Lian, Dan Liang, Dao W. Wang, Caiying Guo, Jie Ma, Ping Zhao, Robert J. Coffey, Qimin Zhan, Guanqing Wu
Journal: Journal of the American Society of Nephrology (2009)

Loss of polycystin-2 (PC2) in mice (Pkd2(-/-)) results in total body edema, focal hemorrhage, structural cardiac defects, abnormal left-right axis, hepatorenal and pancreatic cysts, and embryonic lethality. The molecular mechanisms by which loss of PC2 leads to these phenotypes remain unknown. We generated a model to allow targeted Pkd2 inactivation using the Cre-loxP system. Global inactivation of Pkd2 produced a phenotype identical to Pkd2(-/-) mice with undetectable PC2 protein and perinatal lethality. Using various Cre mouse lines, we found that kidney, pancreas, or time-specific deletion of Pkd2 led to cyst formation. In addition, we developed an immortalized renal collecting duct cell line with inactive Pkd2; these cells had aberrant cell-cell contact, ciliogenesis, and tubulomorphogenesis. They also significantly upregulated beta-catenin, axin2, and cMyc. Our results suggest that loss of PC2 disrupts normal behavior of renal epithelial cells through dysregulation of beta-catenin-dependent signaling, revealing a potential role for this signaling pathway in PC2-associated ADPKD.
Evolutionary Distance Estimation Under Heterogeneous Substitution Pattern Among Lineages
Authors: Koichiro Tamura, Sudhir Kumar
Journal: Molecular Biology and Evolution (2002)

Most of the sophisticated methods to estimate evolutionary divergence between DNA sequences assume that the two sequences have evolved with the same pattern of nucleotide substitution after their divergence from their most recent common ancestor (homogeneity assumption). If this assumption is violated, the evolutionary distance estimated will be biased, which may result in biased estimates of divergence times and substitution rates, and may lead to erroneous branching patterns in the inferred phylogenies. Here we present a simple modification for existing distance estimation methods to relax the assumption of the substitution pattern homogeneity among lineages when analyzing DNA and protein sequences. Results from computer simulations and empirical data analyses for human and mouse genes are presented to demonstrate that the proposed modification reduces the estimation bias considerably and that the modified method performs much better than the LogDet methods, which do not require the homogeneity assumption in estimating the number of substitutions per site. We also discuss the relationship of the substitution and mutation rate estimates when the substitution pattern is not the same in the lineages leading to the two sequences compared.
Inspiratory muscle strength and Borg dyspnoea score
Authors: N.G. Koulouris
Journal: European Respiratory Journal (2010)

In our original article we outlined the type of somato-psychosomatic feedback cycle occurring in panic attacks in chronic obstructive pulmonary disease (COPD) that F. Kummer has further elaborated in his correspondence.In fact, this type of feedback cycle is described in the most widely accepted theory of panic attacks and panic disorder in the physically healthy, the cognitive (or ''catastrophic interpretation'') model [1], and our recent research has supported the applicability of this model to panic in COPD [2][3][4].We agree with F. Kummer that some of the most helpful advice respiratory physicians can give their patients with COPD to prevent them entering the feedback cycle of panic is to use ''pursed-lip breathing'' to help manage their dyspnoea, and to avoid excessive use of shortacting b-agonists.We would caution that for individuals with COPD who have already begun to experience panic attacks, for those who have fully developed panic disorder, and even those who are psychologically vulnerable to panic, this sensible advice in isolation will unfortunately not be a sufficient intervention.However, the type of brief, evidence-based psychological intervention that we have reported, when added to comprehensive pulmonary rehabilitation programmes, can help COPD patients to self-manage their own care more effectively [5], treat panic attacks when already present and prevent the development of panic attacks or panic disorder.A more extended psychological intervention will be required for patients who have fully developed panic disorder [3], but without the inherent risks of benzodiazepine medications in the elderly: dependence, cognitive impairment and falls [6].