tbuckley/cabot-search huggingface dataset:
Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.
Authors: K B Schwarz, B J Arey, K Tolman, S Mahanty
Journal: Journal of Clinical Investigation (1988)

To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage.
New Oxford Textbook of Psychiatry, vols. 1, 2
Authors: JOEL YAGER
Journal: American Journal of Psychiatry (2002)

Our current era of globalization demands international partnering (1).Accordingly, we can now welcome one of the first substantial multinational efforts to develop a global textbook of psychiatry.Three eminent editors, from England, Spain, and the United States, have created a scholarly, erudite, and readable work that will enter the pantheon of outstanding, major textbooks.How
Selective unresponsiveness to the inhibition of p38 MAPK activation by cAMP helps L929 fibroblastoma cells escape TNF-α-induced cell death
Authors: Jing Wang, Ruihong Tang, Ming Lv, Jiyan Zhang, Beifen Shen
Journal: Molecular Cancer (2010)

Abstract Background The cyclic AMP (cAMP) signaling pathway has been reported to either promote or suppress cell death, in a cell context-dependent manner. Our previous study has shown that the induction of dynein light chain (DLC) by cAMP response element-binding protein (CREB) is required for cAMP-mediated inhibition of mitogen-activated protein kinase (MAPK) p38 activation in fibroblasts, which leads to suppression of NF-κB activity and promotion of tumor necrosis factor-α (TNF-α)-induced cell death. However, it remains unknown whether this regulation is also applicable to fibroblastoma cells. Methods Intracellular cAMP was determined in L929 fibroblastoma cells after treatment of the cells with various cAMP elevation agents. Effects of cAMP in the presence or absence of the RNA synthesis inhibitor actinomycin D or small interfering RNAs (siRNAs) against CREB on TNF-α-induced cell death in L929 cells were measured by propidium iodide (PI) staining and subsequent flow cytomety. The activation of p38 and c-Jun N-terminal protein kinase (JNK), another member of MAPK superfamily, was analyzed by immunoblotting. JNK selective inhibitor D-JNKi1 and p38 selective inhibitor SB203580 were included to examine the roles of JNK and p38 in this process. The expression of DLC or other mediators of cAMP was analyzed by immunoblotting. After ectopic expression of DLC with a transfection marker GFP, effects of cAMP on TNF-α-induced cell death in GFP+ cells were measured by PI staining and subsequent flow cytomety. Results Elevation of cAMP suppressed TNF-α-induced necrotic cell death in L929 fibroblastoma cells via CREB-mediated transcription. The pro-survival role of cAMP was associated with selective unresponsiveness of L929 cells to the inhibition of p38 activation by cAMP, even though cAMP significantly inhibited the activation of JNK under the same conditions. Further exploration revealed that the induction of DLC, the major mediator of p38 inhibition by cAMP, was impaired in L929 cells. Enforced inhibition of p38 activation by using p38 specific inhibitor or ectopic expression of DLC reversed the protection of L929 cells by cAMP from TNF-α-induced cell death. Conclusion These data suggest that the lack of a pro-apoptotic pathway in tumor cells leads to a net survival effect of cAMP.
Progressive abdominal pain after acute pancreatitis
Authors: L.-C. Chang, K.-L. Liu, H.-P. Wang
Journal: Gut (2010)

How do descending inputs from the brain control leg motor circuits to change the way an animal walks? Conceptually, descending neurons are thought to function either as command-type neurons, in which a single type of descending neuron exerts a high-level control to elicit a coordinated change in motor output, or through a more distributed population coding mechanism, whereby a group of neurons, each with local effects, act in combination to elicit a global motor response. The <i>Drosophila</i> Moonwalker Descending Neurons (MDNs), which alter leg motor circuit dynamics so that the fly walks backwards, exemplify the command-type mechanism. Here, we identify several dozen MDN target neurons within the leg motor circuits, and show that two of them mediate distinct and highly-specific changes in leg muscle activity during backward walking: LIN156 neurons provide the hindleg power stroke during stance phase; LIN128 neurons lift the legs at the end of stance to initiate swing. Through these two effector neurons, MDN directly controls both the stance and swing phases of the backward stepping cycle. MDN exerts these changes only upon the hindlegs; the fore-and midlegs follow passively through ground contact. These findings suggest that command-type descending neurons can also operate through the distributed control of local motor circuits.
IL-18 might reflect disease activity in mild and moderate asthma exacerbation
Authors: Hiroshi Tanaka, Naomitsu Miyazaki, Kensuke Oashi, Shin Teramoto, Masanori Shiratori, Midori Hashimoto, Mitsuhide Ohmichi, Shosaku Abe
Journal: Journal of Allergy and Clinical Immunology (2001)
STUDIES ON PNEUMONIA VIRUS OF MICE (PVM)
Authors: Frank L. Horsfall, Edward C. Curnen
Journal: The Journal of Experimental Medicine (1946)

The results of neutralization tests with PVM and serum obtained from numerous animal species indicate that antibodies agaiust this virus were present in the blood of all mammalian species tested, as not in that of fowls, and that their incidence in various species was widely different. They indicate, also, that in certain species, particularly the cotton rat, there were marked seasonal variations in the incidence of such antibodies; in the late winter and spring the incidence was much higher than during the summer and fall seasons. Cotton rats and hamsters which did not possess neutralizing antibodies against PVM were susceptible to manifest pulmonary infection with this virus, irrespective of the effects of previous experiments upon them, whereas those which possessed such antibodies were immune. It is suggested that circulating antibodies against PVM were present as a result of preceding infection with a latent virus; either PVM or an agent closely related to it in antigenic composition. Appropriate non-specific stimuli, e.g. the intranasal injection of suspensions of normal chick embryos, induced the development of neutralizing antibodies against PVM with significantly greater frequency in each of three species than occurred in control animals. Materials derived from patients with primary atypical pneumonia yielded results almost identical to those obtained with normal chick embryo suspensions. It is suggested that such materials, like the other non-specific stimuli employed, were effective in evoking a specific antibody response, because they unbalanced an equilibrium which previously existed between animal host and latent pneumotropic virus.
pp60c-src activation in human colon carcinoma.
Authors: C A Cartwright, M P Kamps, A I Meisler, J M Pipas, W Eckhart
Journal: Journal of Clinical Investigation (1989)

We measured the in vitro protein-tyrosine kinase activity of pp60c-src from human colon carcinoma cell lines and tumors. The activity of pp60c-src from six of nine carcinoma cell lines was higher (on average, fivefold as measured by enolase phosphorylation, or eightfold as measured by autophosphorylation) than that of pp60c-src from normal colonic mucosal cells, or human or rodent fibroblasts. Similarly, the activity of pp60c-src from 13 of 21 primary colon carcinomas was five- or sevenfold higher than that of pp60c-src from normal colonic mucosa adjacent to the tumor. The increased pp60c-src activity did not result solely from an increase in the level of pp60c-src protein, suggesting the specific activity of the pp60c-src kinase is elevated in the tumor cells. pp60c-src from colon carcinoma cells and normal colonic mucosal cells was phosphorylated at similar sites. We used immunoblotting with antibodies to phosphotyrosine to identify substrates of protein-tyrosine kinases in colonic cells. Three phosphotyrosine-containing proteins were detected at significantly higher levels in most colon carcinoma cell lines than in normal colonic mucosal cells or human or rat fibroblasts. All colon carcinoma cell lines with elevated pp60c-src in vitro kinase activity, showed increased phosphorylation of proteins on tyrosine in vivo, suggesting the presence of an activated protein-tyrosine kinase(s).
Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome
Authors: Charles Peters, Michael Balthazor, Elsa G. Shapiro, Roberta J. King, Craig Kollman, Janet D. Hegland, Jean Henslee-Downey, Michael E. Trigg, Morton J. Cowan, Jean Sanders, Nancy Bunin, Howard Weinstein, Carl Lenarsky, Peter Falk, Richard Harris, Tom Bowen, Thomas E. Williams, Guy H. Grayson, Phyllis Warkentin, Leonard Sender, Valerie A. Cool, Mary Crittenden, Seymour Packman, Paige Kaplan, Lawrence A. Lockman, James Anderson, William Krivit, Kathryn Dusenbery, John Wagner
Journal: Blood (1996)
Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.
Authors: K Bottomly, P H Maurer
Journal: The Journal of Experimental Medicine (1980)

Responder and nonresponder mice primed with poly-(L-glutamic acid,L-lysine,L-phenylalanine) (GLPhe), the response to which is under the control of immune response (Ir) genes, were used as a source of both types of helper T cells required for a T15 idiotype dominated T-dependent anti-phosphorylcholine (PC) response. It was found that the activity of one of the helper T cells needed for an anti-PC response was under major histocompatibility complex (MHC)-linked Ir gene control, and only GLPhe-primed responder mice could be used as a source of these cells. These T cells (ThMHC) whose presence is required for in vivo T-B collaboration are found in normal and anti-mu-treated mice, and their activity depends on the hapten being physically linked to the carrier molecule. By contrast, the activity of the second helper T cell (ThId) required for a T15-dominated anti-PC response was present in both GLPhe-primed responder and nonresponder mice. The ThId cell set that is missing or deficient in anti-mu treated mice can be restored by the addition of T cells from normal, carrier-primed donors and restimulating with the priming carrier. When T cells from GLPhe-primed donors are used as a source of ThId cells, both responder and nonresponder donors provide helper cells capable of inducing syngeneic B cells to produce a T15 dominated anti-Pc response. These results are interpreted to suggest that idiotype recognizing helper T cells (ThId) recognize antigen independent of known Ir gene products.
Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease
Authors: UG Lalloo, S Lim, R DuBois, PJ Barnes, KF Chung
Journal: European Respiratory Journal (1998)

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.
VERONAL POISONING: RECOVERY AFTER 100 GRAINS
Authors: H. R. Souper
Journal: BMJ (1914)

VERONAL POISONING.r TEDi BsALisW I O IA actual pressure of the flurid, till tlle lung is ultilmiately flattened around its root against tlle inediastinum.When this condition exists the pus would not be likely to gain access to a bronchus.If the abscess occurred on the left side it might burst into the pericardlium.My son, who was a medical student, returned from Dublin for hiis (Christmas holidays.He ha(l always been a wiry, healthy )oy and was never sick, taking great interest in football and all school games.On December 23rd he had a rigor and his temperature went up to 1040.From this date until January 18th his chart resembled a case of tvphoid fever in the third week.He had moist rAles in the chest, with a little cough anid expecto- ration.On January 9th the temperature rose suddenly to 105.0He was delirious all niight and had great perspiration, with pain in the right lunig anid increase of expectoration.This, I thlink, was tJie start of the abscess.The pain gradually increased, with incessant cough and perspiration so copious that blankets lhad to be changed frequently.
Noninvasive evaluation of left ventricular performance based on peak aortic blood acceleration measured with a continuous-wave Doppler velocity meter.
Authors: H N Sabbah, F Khaja, J F Brymer, T M McFarland, D E Albert, J E Snyder, S Goldstein, P D Stein
Journal: Circulation (1986)

Peak aortic blood acceleration is recognized to be a sensitive index of global left ventricular performance. In the present study peak acceleration was assessed noninvasively in patients with a continuous-wave Doppler velocity meter. Peak aortic blood velocity and peak blood acceleration were measured by placing the ultrasonic transducer at the suprasternal notch. Measurements were obtained in 36 patients undergoing diagnostic cardiac catheterization. Peak velocity and acceleration were measured at rest just before left ventriculography. In patients with ejection fractions greater than 60%, peak acceleration was 19 +/- 5 m/sec/sec. In patients with ejection fractions of 41% to 60%, peak acceleration was lower, at 12 +/- 2 m/sec/sec (p less than .001). In patients with ejection fractions of 40% or less, peak acceleration (8 +/- 2 m/sec/sec) was markedly lower than in patients with ejection fractions greater than 60% (p less than .001). Peak acceleration showed a good linear correlation with ejection fraction (r = .90), and a better power fit (r = .93). These results indicate that peak acceleration, measured noninvasively with a continuous-wave Doppler velocity meter, is a useful indicator of global left ventricular performance.
Cardiac Index Is Associated With Brain Aging
Authors: Angela L. Jefferson, Jayandra J. Himali, Alexa S. Beiser, Rhoda Au, Joseph M. Massaro, Sudha Seshadri, Philimon Gona, Carol J. Salton, Charles DeCarli, Christopher J. O'Donnell, Emelia J. Benjamin, Philip A. Wolf, Warren J. Manning
Journal: Circulation (2010)

Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community.Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92).Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.
The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels
Authors: H. J. Stark
Journal: European Respiratory Journal (2005)

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. <i>Aspergillus fumigatus</i> is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial <i>A. fumigatus</i> solution was assessed, to establish if it would have effects on fractional exhaled (F<sub>eNO</sub>) and nasal (F<sub>nNO</sub>) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after <i>A. fumigatus</i> challenge, there was a considerable increase in F<sub>eNO</sub>, and a significant difference was observed between the <i>A. fumigatus</i> and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of F<sub>nNO</sub> or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the <i>A. fumigatus</i> inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of <i>Aspergillus fumigatus</i> elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.
Enhanced Effects of Prostaglandin E1 and Dibutyryl Cyclic AMP upon Human Lymphocytes in the Presence of Cortisol
Authors: John Mendelsohn, Michael M. Multer, Robert F. Boone
Journal: Journal of Clinical Investigation (1973)

The combined effects of cortisol and agents acting through a cyclic AMP-mediated mechanism have been studied in cultures of highly purified human peripheral lymphocytes. Incubation with prostaglandin E(1) (PGE(1)), dibutyryl cyclic AMP, or cortisol results in a concentration-dependent inhibition of [(3)H]-thymidine incorporation by both unstimulated and phytohemagglutinin (PHA)-stimulated lymphocytes, and PHA-induced morphologic transformation is prevented. When cortisol and PGE(1) (or dibutyryl cyclic AMP) are added together to lymphocyte cultures, enhanced inhibitory effects are observed. Incubation of unstimulated or PHA-stimulated lymphocytes with PGE(1) results in an elevation of intracellular cyclic AMP levels within 20 min. The concentration of cyclic AMP gradually returns to base-line levels over a 1-6 h period of time. Cortisol alone does not significantly alter cyclic AMP concentrations. However, incubation with PGE(1) in the presence of cortisol results in a greater stimulation of intracellular cyclic AMP levels than that observed with PGE(1) alone. These findings suggest that cortisol may act synergistically with PGE(1) to elevate lymphocyte cyclic AMP levels and to regulate [(3)H]thymidine incorporation and transformation.
MAPK Phosphorylation of Connexin 43 Promotes Binding of Cyclin E and Smooth Muscle Cell Proliferation
Authors: Scott R. Johnstone, Brett M. Kroncke, Adam C. Straub, Angela K. Best, Clarence A. Dunn, Leslie A. Mitchell, Yelena Peskova, Robert K. Nakamoto, Michael Koval, Cecilia W. Lo, Paul D. Lampe, Linda Columbus, Brant E. Isakson
Journal: Circulation Research (2012)

Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE(-/-)) mice and in C57Bl/6 mice treated with platelet-derived growth factor-BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43(CT)) and produced null phosphorylation Ser>Ala (Cx43(MK4A)/Cx43(CTMK4A)) and phospho-mimetic Ser>Asp (Cx43(MK4D)/Cx43(CTMK4D)) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43(+/+)) and Cx43 null (Cx43(-/-)) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.