tbuckley/cabot-search huggingface dataset:
Activated Interstitial Myofibroblasts Express Catabolic Enzymes and Mediate Matrix Remodeling in Myxomatous Heart Valves
Authors: Elena Rabkin, Masanori Aikawa, James R. Stone, Yoshihiro Fukumoto, Peter Libby, Frederick J. Schoen
Journal: Circulation (2001)

Background The mechanisms of extracellular matrix changes accompanying myxomatous valvular degeneration are uncertain. Methods and Results To test the hypothesis that valvular interstitial cells mediate extracellular matrix degradation in myxomatous degeneration by excessive secretion of catabolic enzymes, we examined the functional characteristics of valvular interstitial cells in 14 mitral valves removed for myxomatous degeneration from patients with mitral regurgitation and in 11 normal mitral valves obtained at autopsy. Immunohistochemical staining assessed (1) cell phenotype using antibodies to α-actin (microfilaments), vimentin and desmin (intermediate filaments), smooth muscle myosin (SM1), and SMemb (a nonmuscle myosin produced by activated mesenchymal cells) and (2) the expression of proteolytic activity using antibodies to collagenases (matrix metalloproteinase [MMP]-1, MMP-13), gelatinases (MMP-2, MMP-9), cysteine endoproteases (cathepsin S and K), and interleukin-1β, a cytokine that can induce secretion of proteolytic enzymes. Although interstitial cells in normal valves stained positively for vimentin, but not α-actin or desmin, cells in myxomatous valves contained both vimentin and α-actin or desmin (characteristics of myofibroblasts). Moreover, cells in myxomatous valves strongly expressed SMemb, MMPs, cathepsins, and interleukin-1β, which were weakly stained in controls. Nevertheless, interstitial cells in both groups strongly expressed procollagen-I mRNA (in situ hybridization), suggesting preserved ability to synthesize collagen in myxomatous valves. Conclusions Interstitial cells in myxomatous valves have features of activated myofibroblasts and express excessive levels of catabolic enzymes, without altered levels of interstitial collagen mRNA. We conclude that valvular interstitial cells regulate matrix degradation and remodeling in myxomatous mitral valve degeneration.
The G Protein–Coupled Receptor 87 Is Necessary for p53-Dependent Cell Survival in Response to Genotoxic Stress
Authors: Yanhong Zhang, Yingjuan Qian, Wenfu Lu, Xinbin Chen
Journal: Cancer Research (2009)

p53 regulates an array of target genes, which mediates p53 tumor suppression by inducing cell cycle arrest, apoptosis, and cell survival. G protein-coupled receptors belong to a superfamily of cell surface molecules and are known to regulate cell proliferation, migration, and survival. Here, we found that G protein-coupled receptor 87 (GPR87) was up-regulated by p53 and by DNA damage in a p53-dependent manner. We also found that p53 directly regulated GPR87 potentially via a p53-responsive element in the GPR87 gene. To investigate the role of GPR87 in the p53 pathway, we generated multiple RKO and MCF7 cell lines in that GPR87 can be inducibly overexpressed or knocked down by a tetracycline-inducible system. We found that overexpression of GPR87 had little effect on cell growth. However, GPR87 knockdown sensitized cancer cells to DNA damage-induced growth suppression via enhanced p53 stabilization and activation. Importantly, the prosurvival activity of GPR87 can be reversed by knockdown of p53. Together, our results suggested that GPR87 is essential for p53-dependent cell survival in response to DNA damage. Thus, due to its expression on the cell surface and its role in cell survival, GPR87 may be explored as a novel therapeutic target for cancer treatment and prevention.
An Address ON CHRONIC INTESTINAL STASIS
Authors: W. A. Lane
Journal: BMJ (1909)

attaoks may be followed by transitory paralysis in he form of aphasia, hemiplegia, monoplegia, etc.It is in cases of doubtful diagnosis .that the pathologist can.fford help by the employment of methods of examina- tion-of the blood and cerebro-spinal fluid, to which I fully referred in the Morison Lectures, but which I will briefly note again, for since I .gave the lectures I have found these methods of great use in the diagnosis of several early doubtful cases of general paralysis.EXAMINATION OF THE CBREBRO-SPINAL FLUID.The Was8ermann-Neis8er-Briick Method.This test may be carried out in the following manner.
What Can Be Learned From Trials Running Short of Patients or Events?
Authors: Gunter von Minckwitz, Valentina Nekljudova, Sibylle Loibl
Journal: Journal of Clinical Oncology (2012)

chemotherapy for locally recurrent or metastatic breast cancer: Safety and efficacy in an open-label study in 2,251 patients. Ann Oncol 22:595-602, 2011 18. Miles D, Chan A, Romieu G, et al: Randomized, double-blind, placebocontrolled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer: AVADO. J Clin Oncol 26:43s, 2008 (suppl 15; abstr 1011) 19. Brufsky A, Rivera RR, Hurvitz SA, et al: Progression-free survival (PFS) in patient subgroups in RIBBON-2, a phase III trial of chemotherapy (chemo) plus or minus bevacizumab (BV) for second-line treatment of HER2-negative, locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 28:119s, 2010 (suppl 15; abstr 1021) 20. Miller KD, Chap LI, Holmes FA, et al: Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:792-799, 2005 21. Bear HD, Tang G, Rastogi P, et al: Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 366:310-320, 2012 22. von Minckwitz G, Eidtmann H, Rezai M, et al: Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366:299-309, 2012 23. Gianni L, Romieu G, Lichinistser M, et al: First results of AVEREL, a randomized phase III trial to evaluate bevacizumab (BEV) in combination with trastuzumab (H) docetaxel (DOC) as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC). Cancer Res 71:S4-S8, 2011 (suppl 24) 24. An SJ, Huang YS, Chen ZH, et al: Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy. Med Oncol [epub ahead of print on April 3, 2011] 25. Peppercorn J, Shapira I, Collyar D, et al: Ethics of mandatory research biopsy for correlative end points within clinical trials in oncology. J Clin Oncol 28:2635-2640, 2010
Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
Authors: Solveig Gretarsdottir, Annette F Baas, Gudmar Thorleifsson, Hilma Holm, Martin den Heijer, Jean-Paul P M de Vries, Steef E Kranendonk, Clark J A M Zeebregts, Steven M van Sterkenburg, Robert H Geelkerken, Andre M van Rij, Michael J A Williams, Albert P M Boll, Jelena P Kostic, Adalbjorg Jonasdottir, Aslaug Jonasdottir, G Bragi Walters, Gisli Masson, Patrick Sulem, Jona Saemundsdottir, Magali Mouy, Kristinn P Magnusson, Gerard Tromp, James R Elmore, Natzi Sakalihasan, Raymond Limet, Jean-Olivier Defraigne, Robert E Ferrell, Antti Ronkainen, Ynte M Ruigrok, Cisca Wijmenga, Diederick E Grobbee, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Viola Vaccarino, Riyaz S Patel, A Maziar Zafari, Allan I Levey, Harland Austin, Domenico Girelli, Pier Franco Pignatti, Oliviero Olivieri, Nicola Martinelli, Giovanni Malerba, Elisabetta Trabetti, Lewis C Becker, Diane M Becker, Muredach P Reilly, Daniel J Rader, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Sigitas Urbonavicius, Bengt Lindblad, Anders Gottsäter, Eleonora Gaetani, Roberto Pola, Philip Wells, Marc Rodger, Melissa Forgie, Nicole Langlois, Javier Corral, Vicente Vicente, Jordi Fontcuberta, Francisco España, Niels Grarup, Torben Jørgensen, Daniel R Witte, Torben Hansen, Oluf Pedersen, Katja K Aben, Jacqueline de Graaf, Suzanne Holewijn, Lasse Folkersen, Anders Franco-Cereceda, Per Eriksson, David A Collier, Hreinn Stefansson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Einar M Valdimarsson, Hulda B Magnadottir, Sigurlaug Sveinbjornsdottir, Isleifur Olafsson, Magnus Karl Magnusson, Robert Palmason, Vilhelmina Haraldsdottir, Karl Andersen, Pall T Onundarson, Gudmundur Thorgeirsson, Lambertus A Kiemeney, Janet T Powell, David J Carey, Helena Kuivaniemi, Jes S Lindholt, Gregory T Jones, Augustine Kong, Jan D Blankensteijn, Stefan E Matthiasson, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2010)
Chunks, bindings, STAR, and Holographic Reduced Representations
Authors: Tony A. Plate
Journal: Behavioral and Brain Sciences (1998)

Much of Halford et al.'s discussion of vector models for representing relations concerns the perceived inadequacies of alternative methods with respect to chunking, binding, systematicity, and resource requirements. Vector-based models for storing relations are in their infancy, however, and the relative merits of different schemes are not so clearly in favor of their STAR scheme as Halford et al. portray.
Rational Psycho-Pharmacology for Patients with Medical Diseases
Authors: D J Greenblatt, R I Shader, S Lofgren
Journal: Annual Review of Medicine (1976)

It is no surprise that psychotropic drugs are commonly administered to  with medical diseases (1, 2). First, non psychiatrist physicians often encounter emo­ tional discomfort in their  with medical diseases. Surveys performed in the Unites States (3-7) and elsewhere (8-10) suggest that a high percentage of ambula­ tory individuals with medical disorders receive psychotropic drugs because of anxi­ ety or insomnia. Studies of drug dispensing patterns (9, 11, 12) indicate that the majority of psychotropic drug prescriptions are written by general practitioners, internists, and surgeons. Well over 50% of hospitalized medical  receive pharmacotherapy for anxiety or insomnia (13-15). Second, a number of individuals with primary emotional disorders-particularly the elderly-have coincident medi­ cal diseases. Finally, in some medical disorders or syndromes, such as intractable hiccups or severe nausea and vomiting, a psychotropic drug (i.e. a phenothiazine) may constitute a treatment of choice (16). This pharmacologic interface of medicine and psychiatry is of considerable impor­ tance. Informed clinicians require an understanding of whether psychotropic drugs can provide symptomatic benefit for their medically ill patients with emotional distress. They should also understand whether the psychotropic drugs they adminis­ ter can influence the clinical course of the medical dise�se and, conversely, whether the response to the psychotropic agent can be affected by characteristics of the patient and the disease state. This article focuses upon such considerations.
The estimation of body density in rugby union football players.
Authors: W Bell
Journal: British Journal of Sports Medicine (1995)

The general regression equation of Durnin and Womersley for estimating body density from skinfold thicknesses in young men, was examined by comparing the estimated density from this equation, with the measured density of a group of 45 rugby union players of similar age. Body density was measured by hydrostatic weighing with simultaneous measurement of residual volume. Additional measurements included stature, body mass and skinfold thicknesses at the biceps, triceps, subscapular and suprailiac sites. The estimated density was significantly different from the measured density (P < 0.001), equivalent to a mean overestimation of relative fat of approximately 4%. A new set of prediction equations for estimating density was formulated from linear regression using the logarithm of single and sums of skinfold thicknesses. Equations were derived from a validation sample (n = 22) and tested on a crossvalidation sample (n = 23). The standard error of the estimate (s.e.e.) of the equations ranged from 0.0058 to 0.0062 g ml-1. The derived equations were successfully crossvalidated. Differences between measured and estimated densities were not significant (P > 0.05), total errors ranging from 0.0067 to 0.0092 g ml-1. An exploratory assessment was also made of the effect of fatness and aerobic fitness on the prediction equations. The equations should be applied to players of similar age and playing ability, and for the purpose of identifying group characteristics. Application of the equations to individuals may give rise to errors of between -3.9% to +2.5% total body fat in two-thirds of cases.
Metformin-Induced Pancreatitis: A possible adverse drug effect during acute renal failure
Authors: F. L. Fimognari
Journal: Diabetes Care (2006)

Metformin-Induced PancreatitisA possible adverse drug effect during acute renal failure A bout 2% of episodes of acute pancreatitis are caused by drugs (1).Phenformin was repeatedly associated with acute pancreatitis (1), but only two case reports highlighted a possible causative role for metformin (2,3).In one case, acute pancreatitis occurred for the coexistence of correct metformin treatment and acute renal failure (2); in the other, metformin overdose was deemed responsible (3).A 61-year-old woman with diabetes and hypercholesterolemia presented after 5 days of vomiting, followed by oliguria and epigastric pain.At home, the therapy of 3 g/day metformin and 80 mg/day fluvastatin was continued, despite symptoms.Laboratory investigations showed metabolic acidosis with normal lactate, creatinine 13 mg/dl, amylase 270 units/l (normal range 30 -110), lipase 1,813 units/l (23-300), and white blood cells 9,000/mm 3 (80% neutrophils).Acute pancreatitis was confirmed by computed tomography.No recognized cause of acute pancreatitis was identified (hypertriglyceridemia, hypercalcemia, alcoholism, gall stones, virus, or trauma).Drugs were suspended, and a treatment of insulin and intravenous fluids normalized amylase, lipase, and blood gases.The patient was discharged with stable creatinine levels of 2.7 mg/dl.She was reexposed to fluvastatin for 1 month, but no symptoms were reported.Available evidence suggests that acute pancreatitis was caused by metformin accumulation, resulting from a combination of drug overdose and acute renal failure, in turn triggered by vomiting in a patient with concealed renal insufficiency.Because renal failure is a contraindication to metformin, rechallenge was performed only for fluvastatin (1), with negative re-
Role of ethnicity in overweight and obese patients with nonalcoholic steatohepatitis
Authors: Romina Lomonaco, Carolina Ortiz-Lopez, Beverly Orsak, Joan Finch, Amy Webb, Fernando Bril, Christopher Louden, Fermin Tio, Kenneth Cusi
Journal: Hepatology (2011)

The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy-proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy; (2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x-ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3-[(3)H] glucose); (5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3-[(3)H] glucose infusion × FPI) and adipose tissue (fasting FFA × FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 ± 2% vs. 24 ± 2%, p = 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis.When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long-term studies are needed to define their risk of disease progression.
Microsatellites Are Molecular Clocks That Support Accurate Inferences about History
Authors: J. X. Sun, J. C. Mullikin, N. Patterson, D. E. Reich
Journal: Molecular Biology and Evolution (2009)

Microsatellite length mutations are often modeled using the generalized stepwise mutation process, which is a type of random walk. If this model is sufficiently accurate, one can estimate the coalescence time between alleles of a locus after a mathematical transformation of the allele lengths. When large-scale microsatellite genotyping first became possible, there was substantial interest in using this approach to make inferences about time and demography, but that interest has waned because it has not been possible to empirically validate the clock by comparing it with data in which the mutation process is well understood. We analyzed data from 783 microsatellite loci in human populations and 292 loci in chimpanzee populations, and compared them with up to one gigabase of aligned sequence data, where the molecular clock based upon nucleotide substitutions is believed to be reliable. We empirically demonstrate a remarkable linearity (r2 > 0.95) between the microsatellite average square distance statistic and sequence divergence. We demonstrate that microsatellites are accurate molecular clocks for coalescent times of at least 2 million years (My). We apply this insight to confirm that the African populations San, Biaka Pygmy, and Mbuti Pygmy have the deepest coalescent times among populations in the Human Genome Diversity Project. Furthermore, we show that microsatellites support unbiased estimates of population differentiation (FST) that are less subject to ascertainment bias than single nucleotide polymorphism (SNP) FST. These results raise the prospect of using microsatellite data sets to determine parameters of population history. When genotyped along with SNPs, microsatellite data can also be used to correct for SNP ascertainment bias.
A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells
Authors: Michelle R Sam, Bruce E Elliott, Christopher R Mueller
Journal: Molecular Cancer (2007)

Abstract We have previously determined that the HGF promoter can be transactivated by a combination of activated Src and wild-type Stat3 in the mouse breast cell lines HC11 and SP1. To determine if this pathway is of relevance for the human disease, a series of human breast and other human cells lines were examined, and the status of key proteins in these cells determined. All of the human breast cell lines exhibited strong transactivation by a combination of activated Src and Stat3. This activation was dependent on a Stat3 recognition element present at nt-95. The exception was the ErbB2 over-expressing cell line SK-BR-3 where Stat3 alone could transactivate HGF though Src augmented this effect. Increased phosphorylation of Stat3 tyrosine 705 was also observed in this line. Analysis of three ovarian cell lines revealed that Src/Stat3 expression was not able to activate the HGF promoter in two of these lines (SKOV3 and IOSE-80PC). Src/Stat3 expression did activate HGF transcription in OVCAR3 cells, but this effect was not mediated by the Stat3 site at nt-95. Stat3 phosphorylation at tyrosine 705 was observed in IOSE-80PC cells, but was insufficient to allow for activation of the HGF promoter. Human kidney (HEK293) and cervical carcinoma (HeLa) cells were also not Src/Stat3 permissive, despite high levels of Stat3 phospho-Y705. These results suggest that human breast cells are a uniquely permissive environment for HGF transactivation by Src/Stat3 which may allow for the inappropriate activation of HGF transcription during the early stages of breast transformation. This could lead to paracrine or autocrine activation of the Met receptor in breast carcinoma cells.
Review: A20‐Binding Inhibitor of NF‐κB Activation 1 Is a Physiologic Inhibitor of NF‐κB: A Molecular Switch for Inflammation and Autoimmunity
Authors: Rachel T. G'Sell, Patrick M. Gaffney, David W. Powell
Journal: Arthritis & Rheumatology (2015)

The transcription factor NF-κB comprises a family of transcription factors critical for inflammatory signaling, and innate and adaptive immunity.1 NF-κB regulates the transcription of genes involved in immuno-inflammatory responses, cell survival, cell cycle progression, and cell adhesion. Activation of NF-κB by specific ligand-receptor interactions induces the expression of pro-inflammatory mediators, which orchestrate the recruitment of immune cells, induce the inflammatory response, and cause tissue injury.2,3 In this way, excessive NF-κB activity is considered harmful and a pathogenic factor in the chronic inflammation of numerous autoimmune disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes, multiple sclerosis, and inflammatory bowel disease.4 Association between overactive NF-κB and autoimmunity emphasizes the importance of tightly controlled NF-κB signaling. One protein that regulates NF-κB signaling and maintains immune homeostasis is the A20 binding inhibitor of NF-κB1 (ABIN1).
Stereopsis Activates V3A and Caudal Intraparietal Areas in Macaques and Humans
Authors: Doris Y. Tsao, Wim Vanduffel, Yuka Sasaki, Denis Fize, Tamara A. Knutsen, Joseph B. Mandeville, Lawrence L. Wald, Anders M. Dale, Bruce R. Rosen, David C. Van Essen, Margaret S. Livingstone, Guy A. Orban, Roger B.H. Tootell
Journal: Neuron (2003)