tbuckley/cabot-search huggingface dataset:
Inducible Nitric Oxide Synthase Inhibition of Weibel-Palade Body Release in Cardiac Transplant Rejection
Authors: Zhiping Qian, Ramona Gelzer-Bell, Shui-xiang Yang, Wangsen Cao, Tomokazu Ohnishi, Barbara A. Wasowska, Ralph H. Hruban, E. Rene Rodriguez, William M. Baldwin, Charles J. Lowenstein
Journal: Circulation (2001)

Background Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear. Methods and Results We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and analyzed tissue sections by immunohistochemistry. We have confirmed that NOS2 increases cardiac allograft survival. We now show that there is less inflammation of cardiac allografts in wild-type hosts than in NOS2-null hosts. Furthermore, staining for von Willebrand factor reveals that the presence of NOS2 is correlated with the presence of Weibel-Palade bodies inside endothelial cells, whereas the absence of NOS2 is correlated with the release of Weibel-Palade bodies. Conclusions Weibel-Palade bodies contain mediators that promote thrombosis and inflammation. Therefore, nitric oxide (NO) may stabilize the vessel wall and prevent endothelial activation in part by inhibiting the release of the contents of Weibel-Palade bodies. Prevention of Weibel-Palade body release might be a mechanism by which NO protects the vessel wall from inflammatory disorders such as atherosclerosis or graft arteriosclerosis.
Intrarenal Conversion of Angiotensin I to Angiotensin II in the Dog
Authors: Joseph Di Salvo, Aron Peterson, Cheryl Montefusco, Margaret Menta
Journal: Circulation Research (1971)

Effects of close intra-arterial injections of angiotensins I and II on changes in renal blood flow and renal vascular resistance were studied in dogs anesthetized with pentobarbital sodium. In the first series of experiments, angiotensin I (0.375 µg) or angiotensin II (0.13 µg) decreased renal blood flow and pressures in a small renal cortical vein and the renal vein. Although renal vascular resistance was markedly increased by angiotensins I or II, these increases did not appear to involve renal venous segments. Responses to angiotensin I occurred when the injected agonist was not allowed to reach the systemic circulation, and were virtually abolished during infusion of SQ 20475, a synthetic pentapeptide (Pyr-Lys-Try-Ala-Pro) that inhibits enzymatic conversion of angiotensin I to angiotensin II. In the second series of experiments, renal vascular responses to intra-arterial injections of angiotensin I (0.375-3.75 µg) and angiotensin II (0.13-1.00 µg) were studied. Responses to angiotensin I, but not those to angiotensin II, were significantly attenuated by SQ 20475. The results suggest that similar renal vascular segments respond to angiotensins I and II. Responses to angiotensin I are probably due to its intrarenal conversion to angiotensin II. Such conversion appears to occur to the extent of about 4%.
Lung Cancer Cell Type and Asbestos Exposure
Authors: Andrew Churg
Journal: JAMA (1985)

It is often claimed that adenocarcinoma is the most frequent type of lung cancer seen in workers exposed to asbestos. Careful review of the published data, however, fails to support this claim. Rather, it seems that all types of lung cancers occur in asbestos workers, and the presence or absence of a specific cell type cannot be used to prove or disprove an association of carcinoma and asbestos exposure.
Inducing Tolerance to a Soluble Foreign Antigen by Encapsulated Cell Transplants
Authors: William E. Blanco-Bose, Bernard L. Schneider, Patrick Aebischer
Journal: Molecular Therapy (2005)

The immune response to soluble antigens constitutes a current clinical problem impeding the development of protein therapeutics. We have developed an encapsulated-cell delivery system, which, transiently combined with an anti-CD154 antibody treatment, allows for the suppression of this immune response and the establishment of long-term secretion of a foreign antigen, human erythropoietin (huEPO). The chronic presence of antigen appears to be required to maintain this tolerance, as a 21-day gap in the exposure to huEPO is sufficient to restore the ability of mice to mount an antibody response. In contrast, chronic huEPO expression maintains tolerance even in the absence of further anti-CD154 treatment. These results suggest that a soluble antigenic protein can be continuously released, without inducing an antibody response, using encapsulated allogeneic cells. The temporary anti-CD154 treatment induces immune unresponsiveness to the delivered antigen, while the immunoprotected cell implant allows for chronic antigen release, favoring the establishment of tolerance.
Comparison of Fetal Mesencephalic Grafts, AAV-delivered GDNF, and Both Combined in an MPTP-induced Nonhuman Primate Parkinson’s Model
Authors: D Eugene Redmond, Caleb R S McEntire, Joseph P Kingsbery, Csaba Leranth, John D Elsworth, Kimberly B Bjugstad, Robert H Roth, Richard J Samulski, John R Sladek
Journal: Molecular Therapy (2013)

We combined viral vector delivery of human glial-derived neurotrophic factor (GDNF) with the grafting of dopamine (DA) precursor cells from fetal ventral mesencephalon (VM) to determine whether these strategies would improve the anti-Parkinson's effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model for Parkinson's disease (PD). Both strategies have been reported as individually beneficial in animal models of PD, leading to clinical studies. GDNF delivery has also been reported to augment VM tissue implants, but no combined studies have been done in monkeys. Monkeys were treated with MPTP and placed into four balanced treatment groups receiving only recombinant adeno-associated virus serotype 5 (rAAV5)/hu-GDNF, only fetal DA precursor cells, both together, or a buffered saline solution (control). The combination of fetal precursors with rAAV5/hu-GDNF showed significantly higher striatal DA concentrations compared with the other treatments, but did not lead to greater functional improvement in this study. For the first time under identical conditions in primates, we show that all three treatments lead to improvement compared with control animals.
Congenital Anomalies of the Carotid Arteries, Including the Carotid-Basilar and Carotid-Vertebral Anastomoses: An Angiographic Study and a Review of the Literature
Authors: Oscar Sugar
Journal: JAMA (1969)

Anyone interested in cerebral and cervical arteriography would benefit from reading and studying this book. In addition to presenting common and uncommon anomalies of the carotid and vertebral arteries, the author has used embryology extensively to explain and understand how these interesting variations come about. The three primitive anastomoses (trigeminal, otic, and hypoglossal) between carotid and basilar arteries are described, but, in addition, the less-well-known suboccipital (proatlantal) and cervical intersegmental anastomoses are illustrated. The numerous connections between internal and external carotid arteries made prominent after occlusive disease of the internal carotid are well described and their relationship to embryological structures pointed out. They are illustrated by ordinary angiograms, subtraction films, stereoscopic films, and diagrams. The references (up to April 1967) are well chosen. The description of the "wonderful net" of arteries which connect internal and external carotid arteries in animals lays the groundwork for understanding the rare human cases included
Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation
Authors: F Palacios, C Abreu, D Prieto, P Morande, S Ruiz, T Fernández-Calero, H Naya, G Libisch, C Robello, A I Landoni, R Gabus, G Dighiero, P Oppezzo
Journal: Leukemia (2014)
Human creativity, cultural evolution, and niche construction
Authors: Dean Keith Simonton
Journal: Behavioral and Brain Sciences (2000)

Cultural evolution may be even more prolific in the generation of new forms than is biological evolution – especially when it takes the form of creative genius. Yet evolutionary theories have tended to overlook the factors that might select for outstanding individual creativity. A recent dual-inheritance theory is outlined and then integrated with the niche-construction theory of Laland et al.
Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.
Authors: P I Lobo, C E Spencer
Journal: Journal of Clinical Investigation (1979)

Studies were designed to investigate whether the suppressor cell systems that regulate the humoral and cell-mediated immune responses belong to the same subsets of T cells or different subsets. Mitogen-activated suppressor cells were simultaneously assayed for their ability to inhibit (a) pokeweed mitogen-induced generation of plasma cells, (b) blastogenic response of lymphocytes to allogeneic cells, and (c) generation of killer cells in the cell-mediated lymphocytotoxicity assay. We found that suppressor cells that inhibited the generation of plasma cells were activated by concanavalin A (Con A) and were both radiation and prednisone sensitive. Suppressors that inhibited the blastogenic response in lymphocytes to allogenic cells were also activated by Con A but differed in that they were both radiation and prednisone resistant. In contrast, suppressors that inhibited the generation of the killer cells were activated with phytohemagglutinin and not Con A. These suppressors were prednisone and radiation resistant. These observations cannot be explained by differences at the pro-suppressor or suppressor activator levels as both T cell subsets are radiosensitive. Alternatively, heterogeneity of suppressor cell systems may explain these differences.
Glucose-Induced Exertional Fatigue in Muscle Phosphofructokinase Deficiency
Authors: R G Haller, S F Lewis
Journal: New England Journal of Medicine (1991)

The exercise capacity of patients with muscle phosphofructokinase deficiency is low and fluctuates from day to day. The basis of this variable exercise tolerance is unknown, but our patients with this disorder report that fatigue of active muscles is more rapid after a high-carbohydrate meal.
Massive arterial thrombosis and oral contraception
Authors: M. E Foster, D E B Powell
Journal: BMJ (1980)

it is a pity that the design was not better.The treatment group received specific and non- specific therapy (exercise therapy and regular supervision from a nurse, with occasional medical review), while the controlled group received neither on leaving hospital.As the non-specific factors were uncontrolled, the conclusion that simple exercise rehabilitation is of benefit is invalid.
Endogenous Positive Allosteric Modulation of GABAA Receptors by Diazepam binding inhibitor
Authors: Catherine A. Christian, Anne G. Herbert, Rebecca L. Holt, Kathy Peng, Kyla D. Sherwood, Susanne Pangratz-Fuehrer, Uwe Rudolph, John R. Huguenard
Journal: Neuron (2013)
Radiation-Induced S-Nitrosylation of ER-α Predisposes MCF-7 Breast Cancer Cells to Aggressive Invasion and Migration.
Authors: R. Tamfu, A. Natarajan, H. Yu, S. Mohan, K. Shanmugasundaram, M. Natarajan, M. Natarajan, M. Natarajan
Journal: Cancer Research (2009)

Abstract The objective of this study is to decipher the potentials of breast cancer cells that survive radiation exposure at clinical doses to acquire invasive and metastatic determinants. In this study we exposed estrogen receptor positive (MCF-7) and negative (MDAMB-231) breast cancer cells to clinical doses of low LET radiation including doses used as single fraction (2Gy), cumulative dose (10Gy) and scattered dose (10cGy). The cells were exposed to 137Cs source at a dose rate of 1.27 Gy/min. The mock irradiated cells were used as controls. The mRNA transcript level, protein expression and protein-protein interaction were analyzed by QPCR/RT-PCR, immunoblotting, immunoprecipitation and mammalian two-hybrid system, respectively. Intracellular nitric oxide (NO) levels were determined by immunofluorescence and electron spin resonance spectroscopy (ESR) using DAF-FM and Fe-MGD as NO traps, respectively. NO-dependent ER-α s-nitrosylation was determined through immunoprecipitating s-nitrosylated proteins from the cell lysates with an s-nitrosylated-cysteine IgG antibody followed by ER-α western blot analysis. Transactivation of ER-α was measured by EMSA and luciferase reporter assay. Cell invasion and migration were examined by co-culture system using thin inserts.Radiation induces eNOS expression and activation through the phosphorylation of eNOS at Ser1177 site resulting in increased bioavailability of NO in a dose- and time-dependent manner. The three-fold bioavailability of NO s-nitrosylates ER-α leading to a two-fold binding of ER-α to ERE. Paradoxically, this binding did not translate into the transcriptional activation of ER-α dependent gene regulation. Altered structure due to s-nitrosylation of ER-α contributes to enhanced cell invasion and cell migration. In consistent with these results, there was an associated 2.3-fold increase in the expression of MMP-2 and MMP-9 and corresponding TIMP-1 decreased expression leading to a 3.5-fold increase in MMP activity. Radiation, while controlling tumor growth, could simultaneously play a significant role in breast cancer relapse and metastasis through the activation of eNOS and the generation of NO. The bioavailability of NO s-nitrosylates ER-α leading to re-defining the genomic functions of ER-α and thereby impart metastatic transformation potentials to ER-α positive breast cancer cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6162.
Integrating genetic, behavioral, and psychometric research in conceptualizing human behavioral traits
Authors: Marcus R. Munafò
Journal: Behavioral and Brain Sciences (2005)

previous research into human traits has reached impressive consensus regarding at least some traits, but recent evidence suggests these to be genetically heterogeneous. this is problematic for theories of the neurobiology of human traits. future research should more closely integrate genetic, behavioral, and psychometric research to arrive at biologically validated measurement instruments, which may be better used to understand the mediating role of these traits in the association between genetic variants and complex behaviors.
Loss of the LAT Adaptor Converts Antigen-Responsive T Cells into Pathogenic Effectors that Function Independently of the T Cell Receptor
Authors: Michael Mingueneau, Romain Roncagalli, Claude Grégoire, Adrien Kissenpfennig, Arkadiusz Miazek, Cristel Archambaud, Ying Wang, Pierre Perrin, Elodie Bertosio, Amandine Sansoni, Sylvie Richelme, Richard M. Locksley, Enrique Aguado, Marie Malissen, Bernard Malissen
Journal: Immunity (2009)
Decreased Absolute Amygdala Volume in Cocaine Addicts
Authors: Nikos Makris, Gregory P. Gasic, Larry J. Seidman, Jill M. Goldstein, David R. Gastfriend, Igor Elman, Matthew D. Albaugh, Steven M. Hodge, David A. Ziegler, Fred S. Sheahan, Verne S. Caviness, Ming T. Tsuang, David N. Kennedy, Steven E. Hyman, Bruce R. Rosen, Hans C. Breiter
Journal: Neuron (2004)
THE ASSOCIATION OF ABNORMAL CIRCADIAN CHANGE IN BODY TEMPERATURE WITH POOR CARDIOVASCULAR PROGNOSIS
Authors: Keishi Saihara, Shuichi Hamasaki, Sanemasa Ishida, Tetsuro Kataoka, Akiko Yoshikawa, Naoya Oketani, Hideki Okui, Takuro Shinsato, Takuro Kubozono, So Kubozono, Shoji Fujita, Satoshi Yoshino, Takuro Takumi, Daisuke Kanda, Takehiko Matsushita, Masayo Usuki, Chuwa Tei
Journal: Journal of the American College of Cardiology (2011)
Case 5-1981
Authors: Lewis Landsberg, A. Kevin Raymond
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 56-year-old man was admitted to the hospital because of hypoglycemia.There was a long history of alcohol abuse, with delirium tremens and hepatic disease. Eight years before admission a left pleural effusion developed, and a diagnosis of pulmonary tuberculosis was established. Chemotherapy was administered for two years, with questionable compliance. Four months before entry an x-ray film of the chest showed a nodule, 4 cm in diameter, in the right lung. An upper gastrointestinal study, an ultrasound study of the pancreas, and a liver-spleen scan were negative. The patient continued to imbibe large volumes of alcoholic . . .
A randomised dose ranging study of recombinant tissue plasminogen activator in acute myocardial infarction
Authors: A J McNeill, J S Shannon, S R Cunningham, D J Flannery, N P S Campbell, M M Khan, G C Patterson, S W Webb, A A J Adgey
Journal: BMJ (1988)

To assess the thrombolytic efficacy and the effect on the systemic fibrinolytic system of recombinant tissue plasminogen activator doses of 20 mg, 50 mg, and 100 mg were compared in a randomised study. Tissue plasminogen activator was infused intravenously over 90 minutes in 50 consecutive patients with acute myocardial infarction of four hours9 duration or less; on average the infusion was started 135 minutes (range 20 to 240) after the onset of pain. The affected artery was patent at the end of the 90 minute infusion in 14/17 (82%) of those who received 100 mg, 12/17 (71%) of those who received 50 mg, and 8/16 (50%) of those who received 20 mg. Regardless of dose, reperfusion rates were significantly better for patients treated within two hours of the onset of symptoms (81%) than for those treated in the third and fourth hours (54%). At the end of the infusion serum fibrinogen concentrations fell to 86% of the preinfusion value after 20 mg, 75% after 50 mg, and 63% after 100 mg, and similar dose dependent changes occurred in plasminogen, α<sub>2</sub> anti-plasmin, and fibrinogen and fibrin degradation products. The mean infarct related regional third ejection fraction was 46% for patients with grade 2 or 3 reperfusion and 35% for those with grade 0 or 1. Ventricular fibrillation occurred in six (12%) patients during the infusion of tissue plasminogen activator, but no late ventricular fibrillation occurred. Bleeding was minimal, reocclusion occurred in three patients, and four patients died from cardiac causes. Recombinant tissue plasminogen activator is an effective thrombolytic agent which produces better reperfusion rates after a 50 or 100 mg dose than after a 20 mg dose. The effect on the systemic fibrinolytic system is dose dependent. Successful reperfusion results in improvement of left ventricular function.
Single Versus Multiple Internal Mammary Artery Grafting for Coronary Artery Bypass
Authors: William R. Burfeind, Donald D. Glower, Andrew S. Wechsler, Robert H. Tuttle, Linda K. Shaw, Frank E. Harrell, J. Scott Rankin
Journal: Circulation (2004)

The long-term clinical advantages of using routine multiple internal mammary artery (IMA) grafts for coronary artery bypass (CAB) are not clear. This study was designed to test the hypothesis that multiple IMA grafts would provide better 15-year outcomes when compared with single IMA and vein grafts.Between 1984 and 1987, 1067 consecutive patients undergoing isolated CAB were referred to 1 surgeon practicing primarily single and another surgeon maximizing multiple IMA grafts (clinical practice trial). A 207-patient subset with multiple IMAs underwent postoperative graft angiography at 1 to 32 weeks to define initial IMA patency. Patients were followed-up yearly, and the groups were analyzed as (I) surgical strategy (surgeon operating) (single=413 versus multiple=654), (II) ultimate operation performed (single=418 versus multiple=449), or (III) single versus multiple coronary systems revascularized with IMAs (single=490 versus multiple=377). Advantages of this study design were that an entire referral population was examined, multiple IMAs were applied to the entire spectrum of baseline patient risk, 15-year follow-up provided a complete prognostic picture, and the subgroups were potentially comparable at baseline. In all 3 analyses, single and multiple groups were statistically similar with respect to baseline, operative, and immediate postoperative variables. Early IMA patency was 98.5% (333/338 grafts patent), validating the quality of IMA procedures. Unadjusted and adjusted 15-year outcome analyses for I, II, and III for death, myocardial infarction, percutaneous coronary intervention, redo coronary bypass, and the composite of all events identified multiple versus single as a significant predictor of outcome for the composite end point in adjusted analysis III (hazard ratio=0.808; 95% CI, 0.689 to 0.948; P=0.009), because of a 5% to 10% absolute reduction in each of the outcome variables at 15 years. Moreover, >50% reduction in reoperation rate was observed at 15 years in every analysis.At 15-year follow-up, multiple IMA grafting was associated with a 19.2% adjusted risk reduction in death and cardiac events, caused by decreases in all adverse end points and fewer reoperations. These data indicate that the clinical advantages of maximizing IMA conduits are significant. Based on this information, it is suggested that multiple IMA grafting to 2 coronary systems should be applied liberally to patients with noncardiac risk profiles predictive of long-term survival.
State of 'Desert Shield' Military Medicine at Deadline Time in the Middle East Crisis
Authors: Phil Gunby
Journal: JAMA (1991)

THIS ISSUE of<i>JAMA</i>is reaching readers at the deadline time—set by the United Nations' Security Council—for Iraq to withdraw from Kuwait. At the same time, many of the US military people who are positioned to enforce the deadline, in combat if necessary, are entering their sixth month of duty in the Middle East without placing excessively heavy demands on their medical system. So far, more than 80 US service people have been killed in accidents associated with this "Desert Shield" deployment. Perhaps four to five times that many have been evacuated to the 11 military hospitals maintained by the US Army and Air Force in the western part of Germany (<i>JAMA</i>. 1989;261:2774-2775) because of illnesses or injuries. The number of US military medical people in the region has never been announced but, by this time, may be approaching 15 000 or more, including enlisted corpsmen who are trained to
Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll‐like receptor 9 in mice
Authors: Hai Huang, John Evankovich, Wei Yan, Gary Nace, Lemeng Zhang, Mark Ross, Xinghua Liao, Timothy Billiar, Jun Xu, Charles T. Esmon, Allan Tsung
Journal: Hepatology (2011)

Sterile inflammatory insults are known to activate innate immunity and propagate organ damage through the recognition of extracellular damage-associated molecular pattern (DAMP) molecules. Although DAMPs such as endogenous DNA and nuclear high-mobility group box 1 have been shown to be critical in sterile inflammation, the role of nuclear histone proteins has not yet been investigated. We report that endogenous histones function as DAMPs after ischemic injury through the pattern recognition receptor Toll-like receptor (TLR) 9 to initiate inflammation. Using an in vivo model of hepatic ischemia/reperfusion (I/R) injury, we show that levels of circulating histones are significantly higher after I/R, and that histone neutralization significantly protects against injury. Injection of exogenous histones exacerbates I/R injury through cytotoxic effects mediated by TLR9 and MyD88. In addition, histone administration increases TLR9 activation, whereas neither TLR9 nor MyD88 mutant mice respond to exogenous histones. Furthermore, we demonstrate in vitro that extracellular histones enhance DNA-mediated TLR9 activation in immune cells through a direct interaction.These novel findings reveal that histones represent a new class of DAMP molecules and serve as a crucial link between initial damage and activation of innate immunity during sterile inflammation.