tbuckley/cabot-search huggingface dataset:
Abstract 13756: Smooth Muscle-specific Deletion of MURC/Cavin-4 Alleviates Pulmonary Arterial Hypertension
Authors: Naohiko Nakanishi, Takehiro Ogata, Kotaro Miyagawa, Tetsuro Hamaoka, Naoki Maruyama, Takeru Kasahara, Tomomi Ueyama
Journal: Circulation (2014)

Background: Pulmonary arterial hypertension (PAH) is a progressive disease associated with a poor prognosis. Caveolin-1 (Cav1) deficiency causes PAH in mice and mutations in gene are identified in patients with PAH. MURC/Cavin-4, a member of the cavin family which regulates caveolar formation and function together with caveolins, regulates Rho/ROCK signaling in cardiomyocytes. Rho/ROCK signaling has been suggested to be involved in PAH. However, roles of MURC/Cavin-4 in the development of PAH remain unknown. Methods and Results: MURC/Cavin-4-floxed (MURCfl/fl) mice and smooth muscle-specific MURC/Cavin-4 (SM22Cre+MURCfl/fl) conditional knockout (cKO) mice were subjected to chronic normobaric hypoxia. cKO mice exhibited attenuation of hypoxia-induced PAH and vascular remodeling compared with MURCfl/fl mice. We then examined roles of MURC/Cavin-4 in pulmonary arterial smooth muscle cells (PASMCs). MURC/Cavin-4 knockdown in human PASMCs (hPASMCs) reduced RhoA activity, proliferation and migration, while MURC...
Pancreatic Adenocarcinoma Clinical Practice Guidelines in Oncology
Authors: Margaret A. Tempero, J. Pablo Arnoletti, Stephen Behrman, Edgar Ben-Josef, Al B. Benson, Jordan D. Berlin, John L. Cameron, Ephraim S. Casper, Steven J. Cohen, Michelle Duff, Joshua D.I. Ellenhorn, William G. Hawkins, John P. Hoffman, Boris W. Kuvshinoff, Mokenge P. Malafa, Peter Muscarella, Eric K. Nakakura, Aaron R. Sasson, Sarah P. Thayer, Douglas S. Tyler, Robert S. Warren, Samuel Whiting, Christopher Willett, Robert A. Wolff
Journal: Journal of the National Comprehensive Cancer Network (2005)

In the year 2005, an estimated 31,800 people will die of pancreatic cancer in the United States. This disease is the fourth most common cause of cancer-related death among men in the United States. Its peak incidence occurs in the seventh and eighth decades of life. Although incidence is roughly equal in the two sexes, African Americans appear to have a higher incidence of pancreatic cancer than white Americans. In these NCCN Pancreatic Adenocarcinoma guidelines, only tumors of the exocrine pancreas are discussed; endocrine tumors from the islets of Langerhans and carcinoid tumors are not included. For the most recent version of the guidelines, please visit NCCN.org
Abstract 20085: Inhibition of Hdac Induces Protective Effects Against Diabetic Cardiomyopathy
Authors: Youfang Chen, Jian Feng Du, Yu Zhao, Ting C Zhao
Journal: Circulation (2014)

Background: It is known that inhibition of histone deacetylases (HDACs) protects the heart against ischemic injury. However, it remains unknown whether HDAC inhibition produces the cardioprotective effect in the diabetic heart. Objective: We sought to determine whether HDAC inhibition preserves cardiac performance and suppresses cardiac remodeling in diabetic cardiomyopathy. Methods: Adult ICR male mice received an intraperitoneal injection (i.p.) of streptozotocin (STZ, 200mg/kg) to establish the diabetic model. Once hyperglycemia was confirmed, diabetic mice received sodium butyrate, a specific HDAC inhibitor (1%) in drinking water on a daily basis. Myocardial function was assessed by echocardiography. Cardiac hypertrophy, fibrosis, and myocyte death were evaluated by histological analysis. Western blot was employed to determine the proteins of signaling pathways. Results: Left ventricular function was depressed in diabetic mice as compared with control group. HDAC inhibition resulted in an improvement in cardiac function in STZ-injected mice (Table1). Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes. Additionally, sodium butyrate reduced interstitial fibrosis and apoptosis, but increased angiogenesis in diabetic myocardium. Notably, glucose transporter type 1 and 4 (GLUT1, GLUT4) and superoxide dismutase (SOD 1) were elevated following HDAC inhibition in the diabetic myocardium. GLUT1 acetylation was increased in diabetic myocardium following HDAC inhibition. Conclusion: HDAC inhibition plays a critical role to reduce cardiac damage in diabetic mice.
Manual of Medical Care of the Surgical Patient
Authors: William George Abel
Journal: JAMA (1986)

This is the third edition of a 302-page spiral-bound manual, which should indicate its popularity. The manual proposes to provide a ready reference for the medical problems encountered by the physician caring for a surgical patient, and within the space limits imposed has succeeded very well. There are 18 short chapters, including "Anesthesia" (for the monanesthesiologist) and "Special Problems of the Aged." The chapter on anesthesia, though interesting, could easily have been omitted, as it adds nothing to the "medical care" format. The chapters vary in quality and suffer from a problem common to all manuals, namely, how to include all pertinent material in a few pages! Despite this limitation, the chapters on the cardiovascular system, the endocrine system, fluids and electrolytes, renal disease, the hematologic system, nutrition, and the respiratory system provide much useful, easily accessible information. The manual in my opinion would be most useful for the medical
Gene-Expression Signatures in Breast Cancer
Authors: Daniel B Kopans
Journal: New England Journal of Medicine (2003)

The study by van de Vijver et al. is of considerable interest with respect
to the biology of breast cancer. However, from
the point of view of the individual patient and her
physician, the sensitivity and specificity of prognostic
profiles are more important than odds ratios.
It is possible to calculate these factors in part from
the results. For example, for all new patients in the
consecutive series (180 patients, listed in Table 2
of the article), the sensitivity and specificity of the
poor prognostic signature are 0.93 (95 percent confidence
interval, 0.81 to 0.98) and 0.53 (95 percent
confidence interval, 0.45 to 0.61), respectively. If
a hypothetical treatment were administered on this
basis, nearly two thirds of the patients with a poor
prognostic signature (65 of 104 patients) would be
overtreated. Thus, the reported genetic signatures
do not seem to be much sharper weapons for daily
practice than other, easier-to-obtain prognostic indicators.
Abstract 2586: Bortezomib reduces preexisting antibodies to recombinant immunotoxins in mice
Authors: Michael L. Manning, Emily Mason-Osann, Masanori Onda, Ira Pastan
Journal: Cancer Research (2014)

Abstract Recombinant immunotoxin (RIT) therapy is limited in patients by neutralizing antibody responses. Most patients with normal immune systems make neutralizing antibodies after one cycle (three doses) of RIT, preventing repeated dosing. Furthermore, some patients have preexisting antibodies from environmental exposure to Pseudomonas exotoxin (PE), the component of the RIT that elicits the neutralizing antibody response. Bortezomib is an FDA-approved proteasome inhibitor which selectively targets and kills plasma cells which are necessary for a neutralizing antibody response. Bortezomib, in combination with methotrexate, rituximab, and cyclophosphamide, was shown to reduce antibody levels &amp;gt;64-fold following enzyme replacement therapy in the clinical setting of Pompe disease. We hypothesized bortezomib may abrogate the neutralizing antibody levels, making dosing of RIT possible in mice already immune to RIT. We immunized BALB/c mice with multiple doses of SS1P, a RIT whose antibody portion targets mesothelin. Antibody titers were determined by immune-capture ELISA. Mice with elevated levels were separated into groups to receive bortezomib (1mg/kg i.v., twice a week for 5.5 weeks) or saline control. Bortezomib treatment lowered the starting antibody titer in mice previously immunized with RIT by an average of 50%, while antibody titers in control mice increased by an average of 20%. Despite success in lowering titers, bortezomib did not abrogate titer in any mice. To further diminish preexisting antibodies, we performed a separate experiment in which mice with preexisting anti-SS1P antibodies received bortezomib with concomitant pentostatin and cyclophosphamide (P/C) therapy. P/C is an immune-depleting regimen already shown to be effective in preventing the onset of new neutralizing antibodies. Combination treatment lowered the starting antibody titer in mice previously immunized with RIT by an average of 73%, while antibody titers in control mice increased by an average of 80%. We have shown that bortezomib reduces, but does not eliminate, antibody titer in mice with preexisting antibodies to RIT. Addition of the immune-depleting P/C regimen further diminishes antibody titers. We are investigating remaining plasma cell populations as a potential source of remaining antibody. Ongoing experiments also include incorporating other FDA-approved agents into our study. Citation Format: Michael L. Manning, Emily Mason-Osann, Masanori Onda, Ira Pastan. Bortezomib reduces preexisting antibodies to recombinant immunotoxins in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2586. doi:10.1158/1538-7445.AM2014-2586
Production of atypical measles in rhesus macaques: Evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody
Authors: Fernando P. Polack, Paul G. Auwaerter, Sok-H. Lee, Hossein C. Nousari, Alexandra Valsamakis, Kristin M. Leiferman, Arwind Diwan, Robert J. Adams, Diane E. Griffin
Journal: Nature Medicine (1999)
Abstract 15783: Lineage Reprogramming of Mouse Fibroblasts to Proliferative and Multipotent Induced Cardiac Progenitor Cells by Defined Factors
Authors: Pratik A Lalit, Max R Salick, Daryl O Nelson, Jayne M Squirrell, Wendy C Crone, Michael Kyba, Daniel J Garry, James A Thomson, Karen M Downs, Gary E Lyons, Timothy J Kamp
Journal: Circulation (2014)

Several studies have reported reprogramming of fibroblasts to induced cardiomyocytes (CMs). However, reprogramming to cardiac progenitor cells (CPCs), which may be more favorable for cell therapy because of their proliferative properties and multipotency, remains to be accomplished. We cloned a library of 22 genes, including cardiac-related transcription factors and chromatin remodeling agents, into a doxycycline inducible lentivirus vector. Fibroblasts used for reprogramming were derived from an Nkx 2.5-EYFP cardiac progenitor reporter mouse model, which when uninfected yielded no EYFP+ cells. However, adult cardiac fibroblasts infected with all 22 factors yielded some EYFP expressing cells only after doxycycline treatment. The factor pool was subsequently reduced to 11, and eventually to 5 factors. After infection with cardiac factors, EYFP+ cells were first observed 4-6 days after doxycycline treatment. By day 20, EYFP+ cells developed into highly proliferative EYFP+ colonies of cells that, upon passaging, exhibited a high nuclear-to-cytoplasmic ratio. Transcriptome analysis and immunocytochemistry of EYFP+ cells revealed up-regulation of CPC markers including Mesp1, Mef2c, Irx4, Gata6, Tbx5, Tbx 20 accompanied by downregulation of fibroblast-specific genes such as Fsp1 and Thy1. Based on lineage specific marker expression, the EYFP+ cells could be differentiated into various cardiac lineages, including cardiomyocytes (α-MHC), smooth muscle (SM-MHC) and endothelium (CD31). Even after doxycycline withdrawal cells remained EYFP+, expressed CPC markers, and retained multipotency for over 30 passages, all indicative of stable reprogramming to an induced CPC (iCPC) state. iCPCs co-cultured with mESC-derived CMs formed intercellular gap junctions and showed synchronous beating accompanied by spontaneous calcium transients. When injected into the cardiac crescent of E8.5 mouse embryos, iCPCs migrated to the developing heart tube and differentiated into MLC2v and cardiac actin expressing CMs. Similar iCPC reprogramming was achieved using adult lung- and tail tip-derived fibroblasts. These results demonstrate the ability of inducible defined factors to reprogram mouse fibroblasts into proliferative and multipotent iCPCs.
Abstract 16007: Functional Comparison of Human Embryonic Stem Cell- versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Rat Ischemic Myocardial Infarction Model
Authors: Wenyi Chen, Johannes Riegler, Elena Matsa, Qi Shen, Haodi Wu, Mike Wang, Joseph D Gold, Joseph Wu
Journal: Circulation (2014)

Introduction: Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as an unlimited cell source for cardiac regenerative therapy. However, the functional equivalency of both approaches has not been previously reported. Here we performed head-to-head comparison on the beneficial effects of ESC-CM and iPSC-CMs in restoring cardiac function in a rat myocardial infarction (MI) model. Methods &amp; Results: Human ESCs and iPSCs were differentiated into cardiomyocytes using small molecules. FACS analysis confirmed ~85% and ~83% of cells differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T, and immunofluorescence staining demonstrated that ESC-CMs and iPSC-CMs have striated sarcomeric structure (Figure A-B). Both ESC-CMs and iPSC-CMs displayed similar maturity for calcium handling (transient amplitude: ΔF/F 0 = 3.8±0.3; time to peak: ~200 ms; 50% transient duration: ~400 ms). qRT-PCR showed that ESC-CMs and iPSC-CMs expressed CASQ2, GJA5, KCNJ2, KCNJ5, MYH6, MYH7, and SCN5A at comparable levels to human fetal heart tissue. Next, ESC-CMs and iPSC-CMs were injected into the left ventricular free wall of infarcted hearts (adult nude rats; n=14, 10, respectively). Cardiac function was assessed by MRI one month post cell injection and the hearts were harvested and stained for human cardiac markers. Both ESC-CMs and iPSC-CMs could engraft in ischemic rat hearts (Figure C). Comprehensive functional analysis with small animal magnetic resonance imaging (MRI), echocardiography, and pressure-volume loop analysis are underway. Conclusion: We set out to perform head to head comparison for the first time that iPSC-CMs may facilitate cardiac repair at comparable levels to ESC-CMs. Unlike allogeneic ESC-CM therapy, autologous iPSC-CMs could be used to overcome immune rejection for cardiac cell transplantation in the future.
796. The HSV-1 iBAC Amplicon Vector for Functional Genomics Studies into the Genetic Mechanisms of Neurodegenerative Disease
Authors: S E Lawler, S., M Ingelsson, Y Saeki, B T Hyman, A P Monaco, E A Chiocca, R Wade-Martins
Journal: Molecular Therapy (2004)

Functional analysis of large genomic loci in cell culture is extremely difficult to perform as genomic DNA transfer to primary cells, such as neurons, is nearly impossible by conventional means. We have developed an efficient infectious genomic DNA delivery vector called the infectious bacterial artificial chromosome, or iBAC, based on the herpes simplex virus type 1 (HSV-1) amplicon. We are applying the system to the analysis of two loci involved in genetic susceptibility to neurodegenerative disease, the microtubule associated protein tau (MAPT, or tau) locus and the α-synuclein (SNCA, or α-syn) locus.
Abstract 15037: Novel Role of Kelch-like ECH-associated Protein 1/NF-E2-related Factor 2 System in Vascular Smooth Muscle Cell Apoptosis Following Vascular Injury
Authors: Takashi Ashino, Masayuki Yamamoto, Satoshi Numazawa
Journal: Circulation (2014)

Abnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after vascular injury are a key event in the neointimal hyperplasia followed by vascular occlusive diseases. To maintain vascular functions, the number of VSMCs is tightly controlled by those proliferation and apoptosis during vascular remodeling. Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system plays a critical role in the oxidative stress response. While Keap1 ubiquitinates Nrf2 for degradation under unstressed conditions, this Keap1 function is abrogated in response to oxidative stress, leading to Nrf2 stabilization and coordinated up-regulation of antioxidant genes. We have previously found that Nrf2 plays an important role in neointimal hyperplasia after vascular injury via regulating platelet-derived growth factor-induced reactive oxygen species-dependent VSMC migration; however, the role of Keap1-Nrf2 system in VSMC apoptosis has not been established. Here we show that TUNEL-positive cells are detected in both the layers of neointima and media, both of which observe alpha-smooth muscle actin positive and high Nrf2-expressed cells, 14 days after transluminal arterial injury in mice. Nrf2 deficient mice show decreased TUNEL-positive cells in neointimal and medial areas (60%) and enhanced neointimal formation (I/M ratio: 152%) 14 days after vascular injury compared with the wild-type mice. In VSMCs isolated from the thoracic aorta of rats, depletion of Keap1 with siRNA increases nuclear Nrf2 (685%) and induces its target genes, including NAD(P)H: quinone oxidoreductase-1 (664%) and heme oxygenase-1 (230%). Functionally, Keap1 depletion increase apoptotic morphological features such as cell shrinkage and nuclear condensation (4114%), annexin V binding (512%), and positive TUNEL staining in VSMCs, which is associated with caspase-3/7 activation (576%). Pretransfection of VSMCs with Nrf2 siRNA inhibits apotosis mediated by Keap1 siRNA. In summary, Keap1-Nrf2 system regulates VSMC apoptosis in the process of neointimal formation, thereby inhibiting VSMC hyperproliferation, which may contribute to the development of neointimal hyperplasia after vascular injury.
Russian doctors sell drugs to misusers to supplement salaries
Authors: Osborn Andrew
Journal: BMJ (2005)

Russia's health professionals are so poorly paid that some have resorted to selling prescription drugs to drug misusers to supplement their incomes, reports in the Russian media say. Twenty medical professionals were convicted in the last year in the region of Rostov, just one of Russia's 89 regions.

The respected Trud (“Labour”) daily newspaper gave a list of doctors, nurses, and pharmacists convicted of such offences. Natalya Arbuzova, a doctor of 20 years' experience, was one example the newspaper gave. She was caught …
Evaluating a Learning Device for Juvenile Diabetic Children
Authors: V Heston James, J Lazar Susan
Journal: Diabetes Care (1980)

The purpose of this study was to determine if knowledge of diabetes could be increased through use of a learning device designed for insulin-dependent diabetic children, aged 7–12 yr. The instrument, consisting of a book and game, combines cognitive and affective elements to provide diabetic information and to reinforce and to evaluate this knowledge in subjects. Serial exposure to the instrument resulted in a significant increase in knowledge and retention of information in 26 experimental subjects. Five subjects receiving one teaching intervention showed an initial increase in knowledge, but without reinforcement, demonstrated minimal retention. Six control subjects, receiving no intervention, showed no increase in knowledge.
Abstract 24: Prenatal Socioeconomic Position is Associated with Adipose Tissue DNA Methylation in Women and Not Men
Authors: Golareh Agha, Andres E Houseman, Karl T Kelsey, Charles B Eaton, Stephen L Buka, Eric B Loucks
Journal: Circulation (2014)

RATIONALE: Adiposity is a major cardiovascular risk factor, suggesting an important role for adipose tissue in development of cardiovascular outcomes. There is evidence that early life adversity has a lasting impact on the development of adiposity, particularly in women. In utero exposure to famine was related to adulthood adiposity in women but not men, and associations between early life socioeconomic adversity and adulthood adiposity is established in women but less so in men. There is interest in epigenetic mechanisms by which early life adversity may program risk for adiposity, and utilizing directly affected tissue such as adipose tissue is ideal for investigating such mechanisms. Objective: To determine whether prenatally-assessed socioeconomic index (SEI) is associated with adulthood genome-wide DNA methylation in blood and adipose tissue, and whether associations differ between men and women. Methods: Participants (aged 44-50 y) were from the New England Family Study birth cohort, born in Providence, RI. Of 400 participants assessed during 2010-2011, a representative subsample of 106 participants (68 women, 38 men) was selected for DNA methylation analyses. SEI was measured prenatally as a composite numerical score, using a weighted percentile of both parents’ educational attainment, occupation, and income relative to the US population. DNA methylation in subcutaneous adipose tissue and peripheral blood leukocytes was evaluated using the Infinium HumanMethylation450K BeadChip. Results: Prenatal SEI was associated with adipose tissue DNA methylation in women (permutation-based omnibus p-values &lt;0.001), but not men or the pooled sample. Associations in women were not attenuated after adjustment for race, current smoking, or mother’s smoking during pregnancy. Prenatal SEI was not related to blood DNA methylation. Conclusion: Results provide mechanistic insight on the association between early life adversity and adulthood adiposity, which is seen mainly in women.
Mechanisms of K+ Transport in Isolated Turtle Urinary Bladder
Authors: Russell F. Husted, Philip R. Steinmetz
Journal: Journal of Clinical Investigation (1982)

Transepithelial K+ movement was studied in vitro in the short-circuited turtle bladder by increasing luminal K+ permeability and by inhibiting the basolateral Na/K pump. Luminal addition of amphotericin B caused net K+ secretion (180±52 nmol/h) compared with net K+ absorption (42±6 nmol/h) in control bladders. Serosal ouabain and luminal amiloride abolished K+ secretion in amphotericin-treated bladders; ouabain restored net absorption (45±16 nmol/h). The direction and rate of net K+ transport are controlled by the relative K+ permeabilities and the Na/K pump sites at the two cell membranes of the epithelium.
Theoretical Principles of Psychosomatic Medicine.
Authors: I. T. Kurt︠s︡in
Journal: Annals of Internal Medicine (1977)

This fairly advanced colour atlas of histology continues the tradition of the once famous Atlas and Textbook of Histology and Microscopic Anatomy by Sobotta, and it contains a series of colour-drawings from that work.It comprises 420 illustrations of all the tissues of the body.Most are in colour, the great majority being stained either with haema- toxylin and eosin or with Mallory-azan.