tbuckley/cabot-search huggingface dataset:
When is it good to believe bad things?
Authors: Joshua M. Ackerman, Jenessa R. Shapiro, Jon K. Maner
Journal: Behavioral and Brain Sciences (2009)

Abstract Positive and negative misbeliefs both may have evolved to serve important adaptive functions. Here, we focus on the role of negative misbeliefs in promoting adaptive outcomes within the contexts of romantic relationships and intergroup interactions. Believing bad things can paradoxically encourage romantic fidelity, personal safety, competitive success, and group solidarity, among other positive outcomes.
β-Lapachone Micellar Nanotherapeutics for Non–Small Cell Lung Cancer Therapy
Authors: Elvin Blanco, Erik A. Bey, Chalermchai Khemtong, Su-Geun Yang, Jagadeesh Setti-Guthi, Huabing Chen, Chase W. Kessinger, Kevin A. Carnevale, William G. Bornmann, David A. Boothman, Jinming Gao
Journal: Cancer Research (2010)

Abstract Lung cancer is the leading cause of cancer-related deaths with current chemotherapies lacking adequate specificity and efficacy. β-Lapachone (β-lap) is a novel anticancer drug that is bioactivated by NAD(P)H:quinone oxidoreductase 1, an enzyme found specifically overexpressed in non–small cell lung cancer (NSCLC). Herein, we report a nanotherapeutic strategy that targets NSCLC tumors in two ways: (a) pharmacodynamically through the use of a bioactivatable agent, β-lap, and (b) pharmacokinetically by using a biocompatible nanocarrier, polymeric micelles, to achieve drug stability, bioavailability, and targeted delivery. β-Lap micelles produced by a film sonication technique were small (∼30 nm), displayed core-shell architecture, and possessed favorable release kinetics. Pharmacokinetic analyses in mice bearing subcutaneous A549 lung tumors showed prolonged blood circulation (t1/2, ∼28 h) and increased accumulation in tumors. Antitumor efficacy analyses in mice bearing subcutaneous A549 lung tumors and orthotopic Lewis lung carcinoma models showed significant tumor growth delay and increased survival. In summary, we have established a clinically viable β-lap nanomedicine platform with enhanced safety, pharmacokinetics, and antitumor efficacy for the specific treatment of NSCLC tumors. Cancer Res; 70(10); 3896–904. ©2010 AACR.
Left Ventricular Concentric Remodeling Is Associated With Decreased Global and Regional Systolic Function: The Multi-Ethnic Study of Atherosclerosis
Authors: Boaz D. Rosen, Thor Edvardsen, Shenghan Lai, Ernesto Castillo, Li Pan, Michael Jerosch-Herold, Shantanu Sinha, Richard Kronmal, Donna Arnett, John R. Crouse, Susan R. Heckbert, David A. Bluemke, Joao A.C. Lima
Journal: Circulation (2005)

The transition from compensatory concentric remodeling to myocardial failure is not completely understood in humans. To investigate determinants of incipient myocardial dysfunction, we examined the association between concentric remodeling and regional LV function in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA).Myocardial tagged MRI was performed. Regional myocardial function expressed as peak systolic midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric remodeling determined by the ratio of left ventricular mass to end-diastolic volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended to be lower only in the fifth compared with the first quintile of M/V ratio (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally heterogeneous but was particularly prominent in the LAD region in men (test for trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and left circumflex artery territories, these associations were less marked in both genders.In this cross-sectional study of asymptomatic individuals, concentric left ventricular remodeling was related to decreased regional systolic function. The reduction in regional function, which was more pronounced in the left anterior descending coronary artery territory, may reflect the local transition from compensatory remodeling to myocardial dysfunction.
Establishment of an inbred line of mice that express a synergistic immune defect precluding in vitro responses to type 1 and type 2 antigens, B cell mitogens, and a number of T cell-derived helper factors.
Authors: J J Mond, G Norton, W E Paul, I Scher, F D Finkelman, S House, M Schaefer, P K Mongini, C Hansen, C Bona
Journal: The Journal of Experimental Medicine (1983)

Introduction of the CBA/N X-linked gene into C3H mice has resulted in the establishment of a new strain of mice that has profound immunologic defects. B cells from these mice show significantly impaired in vitro immune responses to the T cell-independent type 1 antigen trinitrophenyl-Brucella abortus (TNP-BA) as well as markedly reduced proliferative responses to a number of B cell mitogens when compared with the responses of the parental control mice. The in vivo response of such mice to TNP-BA is, however, comparable to that of CBA/N mice. Furthermore, B cells from C3.CBA/N mice are unresponsive to the plaque-forming cell enhancing effects induced by EL4-derived supernatant in the presence of TNP-BA, unlike B cells obtained from CBA/N or C3H/Hen mice whose responsiveness to TNP-BA can be significantly enhanced in the presence of EL4-derived supernatant. The model we have presented to best explain these results suggests that B cells from C3.CBA/N mice can be stimulated only under conditions in which they can interact with carrier-specific T cell help and not under conditions where factor-dependent responses are dominant.
Remarks ON SOME VARIETIES OF HERNIA IN CHILDREN: (After Radical Cure in 152 Cases.)
Authors: E. S. Carmichael
Journal: BMJ (1906)

icleal is to aim at improved metlhods of exact diagnosis and careful and metlhodical examiniationi of every case.Certainily surgery should aim at the preveiitioni of serious complications of existing disease, but I do not find that physicians are prepared to lhand every case of gastric ulcer over to the suLrgeon for the performance of gastro- eniterostomy, or, for the matter of that, every case of catarrlral appenidicitis for., removal of the offending organ.
Effect of chronic ethanol ingestion on enterocyte turnover in rat small intestine.
Authors: R Mazzanti, W J Jenkins
Journal: Gut (1987)

Whether chronic ethanol ingestion significantly damages the small intestine remains controversial. To clarify this we have analysed the morphology of the small intestinal epithelium and quantified its renewal in chronically ethanol fed rats. Twenty adult male rats were pair fed for 28 days a nutritionally adequate liquid diet containing either ethanol as 36% of total calories or an isocaloric diet in which fat substituted for ethanol. Crypt cell production rate was determined in the jejunum and ileum by the metaphase arrest method. Weight gain and small intestinal morphology were similar in ethanol fed and control rats, but enterocyte turnover was significantly reduced in the jejunum (p less than 0.05) and ileum (p less than 0.01) of the ethanol fed rats. This effect of ethanol on the small intestine is probably systemic rather than local, because the changes in jejunum and ileum were similar, and it may contribute to the development of malnutrition in chronic alcoholics.
Favism in the African type of glucose-6-phosphate dehydrogenase deficiency (A-).
Authors: S Galiano, G F Gaetani, A Barabino, F Cottafava, H Zeitlin, M Town, L Luzzatto
Journal: BMJ (1990)

Susceptibility to haemolytic anaemia after ingestion of fava beans has been investigated extensively in the Mediterranean, but favism has also been observed in other countries' including England,2 where variants of glucose-6-phosphate dehydrogenase other than the Mediterranean variant have been responsible. In general, all patients have very low glucose-6-phosphate dehydrogenase activity in red cells (<5% of normal activity). Favism is widely believed not to occur in subjects with the glucose-6-phosphate dehydrogenase A variant, which has a higher residual activity (10-20% of normal) and is present mainly in people of African origin. We report on three patients with the A-variant who suffered typical attacks of clinical favism.
Prognostic value of serum β2-microglobulin in HIV infection
Authors: J Pedreira, A Castro, C Pereiro, C Barbuzano, Alexander Krämer, JamesJ Goedert, Helmut Wachter, Dietmar Fuchs, Pere Domingo, Esteban Martinez, Cecilia Martinez, Monserrat Fuster, Mariano Cortes, MaríaA Sambeat, Josep Ris, Josep Cadafalch
Journal: The Lancet (1992)
Myocardial infarction after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced magnetic resonance imaging
Authors: Willem G van Dockum, Folkert J ten Cate, Jurrien M ten Berg, Aernout M Beek, Jos W.R Twisk, Jeroen Vos, Mark B.M Hofman, Cees A Visser, Albert C van Rossum
Journal: Journal of the American College of Cardiology (2004)
FULL-THICKNESS SUPRASPINATUS TEARS DEMONSTRATE SIGNIFICANT DETERIORATION OF MUSCLE REGENERATIVE POTENTIAL
Authors: K Lundgreen, Ø Lian, A Scott, L Engebretsen
Journal: British Journal of Sports Medicine (2013)

Introduction Rotator cuff tendinopathy is a significant source of musculoskeletal disability. Accompanying muscle changes may be important determinants of the prognosis. The aim of this study was to compare histological muscle changes in partial-thickness to full-thickness tears of the supraspinatus tendon. Methods Muscle biopsies of nine partially torn and 15 fully torn supraspinatus tendons were compared histologically. H&amp;E staining was performed to assess degenerative changes. Immunohistochemistry was used to assess slow and fast myosin heavy chains (type I and II fibres; Anti-slow skeletal myosin heavy chain antibody and Anti-fast skeletal myosin heavy chain antibody), satellite cells (CD56), proliferation (Ki67) and apoptotic cells (activated caspase-3; Asp175). Results Full-thickness tears demonstrated significant atrophy of both slow (type I) and fast (type II) myosin heavy chains compared to partial tears. The area ratio of type II to type I was doubled in full-thickness tears. Partial thickness tears revealed significantly more satellite cells and proliferative activity than full-thickness tears. There was no detectable apoptosis using an antibody recognising active caspase-3. Discussion Progression of rotator cuff tendinopathy is accompanied by a change in muscle fibre phenotype from endurance type I fibres to type II fibres more prone to fatigue, illustrating an aspect of muscle disuse. The rotator cuff muscle's ability to regenerate appears to be reduced when a full-thickness tear is established. Apoptosis does not appear to be of importance in muscle changes accompanying rotator cuff tendinopathy.
A Germline DNA Polymorphism Enhances Alternative Splicing of the <i>KLF6</i> Tumor Suppressor Gene and Is Associated with Increased Prostate Cancer Risk
Authors: Goutham Narla, Analisa DiFeo, Helen L. Reeves, Daniel J. Schaid, Jennifer Hirshfeld, Eldad Hod, Amanda Katz, William B. Isaacs, Scott Hebbring, Akira Komiya, Shannon K. McDonnell, Kathleen E. Wiley, Steven J. Jacobsen, Sarah D. Isaacs, Patrick C. Walsh, S. Lilly Zheng, Bao-Li Chang, Danielle M. Friedrichsen, Janet L. Stanford, Elaine A. Ostrander, Arul M. Chinnaiyan, Mark A. Rubin, Jianfeng Xu, Stephen N. Thibodeau, Scott L. Friedman, John A. Martignetti
Journal: Cancer Research (2005)

Abstract Prostate cancer is a leading and increasingly prevalent cause of cancer death in men. Whereas family history of disease is one of the strongest prostate cancer risk factors and suggests a hereditary component, the predisposing genetic factors remain unknown. We first showed that KLF6 is a tumor suppressor somatically inactivated in prostate cancer and since then, its functional loss has been further established in prostate cancer cell lines and other human cancers. Wild-type KLF6, but not patient-derived mutants, suppresses cell growth through p53-independent transactivation of p21. Here we show that a germline KLF6 single nucleotide polymorphism, confirmed in a tri-institutional study of 3,411 men, is significantly associated with an increased relative risk of prostate cancer in men, regardless of family history of disease. This prostate cancer–associated allele generates a novel functional SRp40 DNA binding site and increases transcription of three alternatively spliced KLF6 isoforms. The KLF6 variant proteins KLF6-SV1 and KLF6-SV2 are mislocalized to the cytoplasm, antagonize wtKLF6 function, leading to decreased p21 expression and increased cell growth, and are up-regulated in tumor versus normal prostatic tissue. Thus, these results are the first to identify a novel mechanism of self-encoded tumor suppressor gene inactivation and link a relatively common single nucleotide polymorphism to both regulation of alternative splicing and an increased risk in a major human cancer.
Inhibiting TGF-β signaling restores immune surveillance in the SMA-560 glioma model
Authors: Thomas-Toan Tran, Martin Uhl, Jing Ying Ma, Lisa Janssen, Venkataraman Sriram, Steffen Aulwurm, Irene Kerr, Andrew Lam, Heather K. Webb, Ann M. Kapoun, Darin E. Kizer, Glenn McEnroe, Barry Hart, Jonathan Axon, Alison Murphy, Sarvajit Chakravarty, Sundeep Dugar, Andrew A. Protter, Linda S. Higgins, Wolfgang Wick, Michael Weller, Darren H. Wong
Journal: Neuro-Oncology (2007)

Transforming growth factor-beta (TGF-beta) is a proinvasive and immunosuppressive cytokine that plays a major role in the malignant phenotype of gliomas. One novel strategy of disabling TGF-beta activity in gliomas is to disrupt the signaling cascade at the level of the TGF-beta receptor I (TGF-betaRI) kinase, thus abrogating TGF-beta-mediated invasiveness and immune suppression. SX-007, an orally active, small-molecule TGF-betaRI kinase inhibitor, was evaluated for its therapeutic potential in cell culture and in an in vivo glioma model. The syngeneic, orthotopic glioma model SMA-560 was used to evaluate the efficacy of SX-007. Cells were implanted into the striatum of VM/Dk mice. Dosing began three days after implantation and continued until the end of the study. Efficacy was established by assessing survival benefit. SX-007 dosed at 20 mg/kg p.o. once daily (q.d.) modulated TGF-beta signaling in the tumor and improved the median survival. Strikingly, approximately 25% of the treated animals were disease-free at the end of the study. Increasing the dose to 40 mg/kg q.d. or 20 mg/kg twice daily did not further improve efficacy. The data suggest that SX-007 can exert a therapeutic effect by reducing TGF-beta-mediated invasion and reversing immune suppression. SX-007 modulates the TGF-beta signaling pathway and is associated with improved survival in this glioma model. Survival benefit is due to reduced tumor invasion and reversal of TGF-beta-mediated immune suppression, allowing for rejection of the tumor. Together, these results suggest that treatment with a TGF-betaRI inhibitor may be useful in the treatment of glioblastoma.
Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes
Authors: Satoru Sonoke, Toshihiro Ueda, Kae Fujiwara, Yohei Sato, Kazuchika Takagaki, Kazuko Hirabayashi, Tadaaki Ohgi, Junichi Yano
Journal: Cancer Research (2008)

The pharmacokinetics and antitumor activity of pegylated small interfering RNA (siRNA)/cationic liposome complexes were studied after systemic administration to mice. We designed pegylated-lipid carriers for achieving increased plasma concentrations of RNA and hence improved accumulation of RNA in tumors by the enhanced permeability and retention effect. We compared the pharmacokinetics of siRNA complexed with liposomes incorporating pegylated lipids with longer (C-17 or C-18), shorter (C-12 to C-16), or unsaturated (C-18:1) acyl chains. When longer acyl chains were used, the plasma concentrations of siRNA obtained were dramatically higher than when shorter or unsaturated chains were used. This may be explained by the higher gel-to-liquid-crystalline phase-transition temperature (Tc) of lipids with longer acyl chains, which may form more rigid liposomes with reduced uptake by the liver. We tested a siRNA that is sequence specific for the antiapoptotic bcl-2 mRNA complexed with a pegylated liposome incorporating a C-18 lipid (PEG-LIC) by i.v. administration in a mouse model of human prostate cancer. Three-fold higher accumulation of RNA in the tumors was achieved when PEG-LIC rather than nonpegylated liposomes was used, and sequence-specific antitumor activity was observed. Our siRNA/PEG-LIC complex showed no side effects on repeated administration and the strength of its antitumor activity may be attributed to its high uptake by the tumors. Pegylation of liposomes improved the plasma retention, uptake by s.c. tumors, and antitumor activity of the encapsulated siRNA. PEG-LIC is a promising candidate for siRNA cancer therapy.
Love's a funny thing
Authors: Liam Farrell
Journal: BMJ (2004)

This is a delicate and touchy subject, but I feel it must be addressed. I recently met a large, fat acquaintance whom I cordially dislike, for reasons that will soon become obvious, and who told me he'd had a hip replacement.

“And how have you been since?” I asked, out of politeness, not really caring, my emotional commitment stalled somewhere between apathy and pity.

“Very sore to start with, but much better now,” he leered, drooling beer …
Impact of Malpractice Reforms on the Supply of Physician Services
Authors: Daniel P. Kessler
Journal: JAMA (2005)

ContextProponents of restrictions on malpractice lawsuits claim that tort reform will improve access to medical care.ObjectiveTo estimate the effects of changes in state malpractice law on the supply of physicians.DesignDifferences-in-differences regression analysis that matched data on the number of physicians in each state between 1985 and 2001 from the American Medical Association's Physician Masterfile with data on state tort laws and state demographic, political, population, and health care market characteristics.Main Outcome MeasureEffect on physician supply of "direct" malpractice reforms that reduce the size of awards (eg, caps on damages).ResultsThe adoption of "direct" malpractice reforms led to greater growth in the overall supply of physicians. Three years after adoption, direct reforms increased physician supply by 3.3%, controlling for fixed differences across states, population, states' health care market and political characteristics, and other differences in malpractice law. Direct reforms had a larger effect on the supply of nongroup vs group physicians, on the supply of most (but not all) specialties with high malpractice insurance premiums, on states with high levels of managed care, and on supply through retirements and entries than through the propensity of physicians to move between states. Direct reforms had similar effects on less experienced and more experienced physicians.ConclusionTort reform increased physician supply. Further research is needed to determine whether reform-induced increases in physician supply benefited patients.
14-3-3 protein in the cerebrospinal fluid of patients with acute transverse myelitis
Authors: David N Irani, Douglas A Kerr
Journal: The Lancet (2000)

The eventual recovery of patients with acute transverse myelitis is variable and can be difficult to predict on the basis of the presenting clinical and radiographic features. We find that an early accumulation of the 14-3-3 protein occurs exclusively in the cerebrospinal fluid of patients who show little or no recovery of neurological function and therefore could serve as a helpful prognostic indicator in this disorder.
Bone Morphogenetic Proteins in Vascular Calcification
Authors: Keith A. Hruska, Suresh Mathew, Georges Saab
Journal: Circulation Research (2005)

Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The bone morphogenetic proteins (BMPs) are important regulators in orthotopic bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2 , or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC.
A Critical Role for Lymphotoxin-β Receptor in the Development of Diabetes in Nonobese Diabetic Mice
Authors: Rachel Ettinger, Sibyl H. Munson, Cheng-Chi Chao, Mary Vadeboncoeur, Jon Toma, Hugh O. McDevitt
Journal: The Journal of Experimental Medicine (2001)

To assess the role of lymphotoxin-β receptor (LTβR) in diabetes pathogenesis, we expressed an LTβR–Fc fusion protein in nonobese diabetic (NOD) mice. The fusion protein was expressed in the embryo, reached high levels for the first 2 wk after birth, and then declined progressively with age. High expression of LTβR–Fc blocked diabetes development but not insulitis. After the decline in chimeric protein concentration, mice became diabetic with kinetics similar to the controls. Early expression of fusion protein resulted in disrupted splenic architecture. However, primary follicles and follicular dendritic cells, but not marginal zones, developed in aged mice. Hence, LTβR signaling is required for diabetes development and regulates follicular and marginal zone structures via qualitatively or quantitatively distinct mechanisms.