tbuckley/cabot-search huggingface dataset:
Balloon injury and interleukin-1 beta induce nitric oxide synthase activity in rat carotid arteries.
Authors: G A Joly, V B Schini, P M Vanhoutte
Journal: Circulation Research (1992)

Experiments were performed to investigate whether balloon injury induces nitric oxide synthase activity in the blood vessel wall. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and excised either immediately (t = 0), 6, or 24 hours after the procedure, with those in control right carotid arteries (with and without endothelium). Phenylephrine evoked comparable concentration-dependent contractions in balloon-injured (t = 0) and control carotid arteries without endothelium, whereas those in control arteries with endothelium were depressed. In the balloon-injured carotid arteries (6 and 24 hours), the concentration-contraction curves to phenylephrine were shifted to the right compared with those observed in balloon-injured arteries (t = 0). In balloon-injured carotid arteries (6 hours), the hyporeactivity to phenylephrine was enhanced by superoxide dismutase. In balloon-injured carotid arteries (24 hours), nitro-L-arginine and methylene blue restored full contractions, whereas superoxide dismutase potentiated the hyporesponsiveness to phenylephrine. The depressed contractions were associated with a concomitant increase in the basal level of cGMP; this production was abolished by nitro-L-arginine. The depression of the concentration-contraction curves to phenylephrine and the increase of the tissue level of cGMP induced by interleukin-1 beta (4 hours) were more pronounced in balloon-injured arteries (24 hours) than in control arteries without endothelium. The effects of interleukin-1 beta were inhibited by nitro-L-arginine. These observations indicate that in vivo endothelial injury of the rat carotid arteries induces the production of nitric oxide from L-arginine in the blood vessel wall, an effect which is potentiated by interleukin-1 beta.
Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation
Authors: Benoît Salomon, Jeffrey A. Bluestone
Journal: Annual Review of Immunology (2001)

Recent advances in the understanding of T cell activation have led to new therapeutic approaches in the treatment of immunological disorders. One attractive target of intervention has been the blockade of T cell costimulatory pathways, which result in more selective effects on only those T cells that have encountered specific antigen. In fact, in some instances, costimulatory pathway antagonists can induce antigen-specific tolerance that prevents the progression of autoimmune diseases and organ graft rejection. In this review, we summarize the current understanding of these complex costimulatory pathways including the individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules. We present evidence that suggests that multiple mechanisms contribute to CD28/B7-mediated T cell costimulation in disease settings that include expansion of activated pathogenic T cells, differentiation of Th1/Th2 cells, and the migration of T cells into target tissues. Additionally, the negative regulatory role of CTLA-4 in autoimmune diseases and graft rejection supports a dynamic but complex process of immune regulation that is prominent in the control of self-reactivity. This is most apparent in regulation of the CD4 + CD25 + CTLA-4 + immunoregulatory T cells that control multiple autoimmune diseases. The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed.
HIGH DOSAGES OF MEPROBAMATE IN CHRONIC SCHIZOPHRENIA
Authors: LAURENCE H. SNOW, KARL RICKELS, HAROLD H. MORRIS
Journal: American Journal of Psychiatry (1962)

1. Meprobamate in high dosage seems to be of value in the treatment of some chronic schizophrenic patients. If it is, it will exert its clinical effects in a relatively short time. 2. High dosage meprobamate seems efficacious in the facilitation of abreactive recall, even when the drug alone is not sufficient to bring about a clinical change. 3. The absence of side-effects other than transient somnolence makes meprobamate a relatively easy drug to use in a controlled inpatient setting. 4. Further studies seem indicated to evaluate adequately large dosage meprobamate therapy in schizophrenia.
Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia
Authors: P. M. Wong, A. N. Lees, J. Louw, F. Y. Lee, N. French, K. Gain, C. P. Murray, A. Wilson, D. C. Chambers
Journal: European Respiratory Journal (2008)

Improved survival following extreme preterm birth complicated by bronchopulmonary dysplasia (BPD) is resulting in an increasing number of affected infants surviving to adulthood. The aim of the present pilot study was to describe the functional and structural pulmonary sequelae of moderate and severe BPD in a population of adult survivors. All babies were cared for at one institution (King Edward Memorial Hospital, Subiaco, Australia). Subjects born between 1980 and 1987 with birthweight <1,500 g and requiring supplementary oxygen at 36 weeks post-menstrual age were identified from a complete neonatal database and recruited prospectively. Local physicians were concurrently asked to refer suitable patients. Demographics, respiratory symptoms and examination results, pulmonary function tests and computed tomography images were acquired. In total, 21 subjects were studied. Of these, 12 were female, the median (range) age was 19 (17-33) yrs and 15 (71%) had persistent respiratory symptoms. The median (range) forced expiratory volume in one second (FEV(1)) z-score was -0.77 (-8.20-1.37), the forced expiratory flow at 25-75% of forced vital capacity was -1.81 (-6.00-0.75) and the diffusing capacity of the lung for carbon monoxide was -5.04 (-13.17- -1.24). Computed tomography was carried out on 19 subjects and all had abnormal findings, with emphysema being the most common, present in 84% of subjects. The extent of radiological emphysema was inversely related to the FEV(1) z-score. Young adult survivors of moderate and severe bronchopulmonary dysplasia may be left with residual functional and characteristic structural pulmonary abnormalities, most notably emphysema.
High Mobility Group 1 Protein (Hmg-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes
Authors: Ulf Andersson, Haichao Wang, Karin Palmblad, Ann-Charlotte Aveberger, Ona Bloom, Helena Erlandsson-Harris, Alfred Janson, Riikka Kokkola, Minghuang Zhang, Huan Yang, Kevin J. Tracey
Journal: The Journal of Experimental Medicine (2000)

Lipopolysaccharide (LPS) is lethal to animals because it activates cytokine release, causing septic shock and tissue injury. Early proinflammatory cytokines (e.g., tumor necrosis factor [TNF] and interleukin [IL]-1) released within the first few hours of endotoxemia stimulate mediator cascades that persist for days and can lead to death. High mobility group 1 protein (HMG-1), a ubiquitous DNA-binding protein, was recently identified as a “late” mediator of endotoxin lethality. Anti–HMG-1 antibodies neutralized the delayed increase in serum HMG-1, and protected against endotoxin lethality, even when passive immunization was delayed until after the early cytokine response. Here we examined whether HMG-1 might stimulate cytokine synthesis in human peripheral blood mononuclear cell cultures. Addition of purified recombinant HMG-1 to human monocyte cultures significantly stimulated the release of TNF, IL-1α, IL-1β, IL-1RA, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and MIP-1β; but not IL-10 or IL-12. HMG-1 concentrations that activated monocytes were within the pathological range previously observed in endotoxemic animals, and in serum obtained from septic patients. HMG-1 failed to stimulate cytokine release in lymphocytes, indicating that cellular stimulation was specific. Cytokine release after HMG-1 stimulation was delayed and biphasic compared with LPS stimulation. Computer-assisted image analysis demonstrated that peak intensity of HMG-1–induced cellular TNF staining was comparable to that observed after maximal stimulation with LPS. Administration of HMG-1 to Balb/c mice significantly increased serum TNF levels in vivo. Together, these results indicate that, like other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1), extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine synthesis.
Incidence of Diabetes and Prediabetes and Predictors of Progression Among Asian Indians: 10-Year Follow-up of the Chennai Urban Rural Epidemiology Study (CURES)
Authors: Ranjit Mohan Anjana, Coimbatore Subramanian Shanthi Rani, Mohan Deepa, Rajendra Pradeepa, Vasudevan Sudha, Haridas Divya Nair, Nagarajan Lakshmipriya, Sivasankaran Subhashini, Valsalakumari Sreekumarannair Binu, Ranjit Unnikrishnan, Viswanathan Mohan
Journal: Diabetes Care (2015)

There are few data on the incidence rates of diabetes and prediabetes (dysglycemia) in Asian Indians. This article presents the incidence of diabetes and prediabetes and the predictors of progression in a population-based Asian Indian cohort.Data on progression to diabetes and prediabetes from 1,376 individuals, a subset of 2,207 of the Chennai Urban Rural Epidemiology Study (CURES) cohort (phase 3) with normal glucose tolerance (NGT) or prediabetes at baseline, who were followed for a median of 9.1 years (11,629 person-years), are presented. During follow-up, 534 died and 1,077 with NGT and 299 with prediabetes at baseline were reinvestigated in a 10-year follow-up study. Diabetes and prediabetes were diagnosed based on the American Diabetes Association criteria. Incidence rates were calculated and predictors of progression to prediabetes and/or diabetes were estimated using the Cox proportional hazards model.The incidence rates of diabetes, prediabetes, and "any dysglycemia" were 22.2, 29.5, and 51.7 per 1,000 person-years, respectively. Among those with NGT, 19.4% converted to diabetes and 25.7% to prediabetes, giving an overall conversion rate to dysglycemia of 45.1%. Among those with prediabetes, 58.9% converted to diabetes. Predictors of progression to dysglycemia were advancing age, family history of diabetes, 2-h plasma glucose, glycated hemoglobin (HbA1c), low HDL cholesterol, and physical inactivity.Asian Indians have one of the highest incidence rates of diabetes, with rapid conversion from normoglycemia to dysglycemia. Public health interventions should target modifiable risk factors to slow down the diabetes epidemic in this population.
Triiodothyronine stimulates maturation of porcine growth-plate cartilage in vitro.
Authors: W M Burch, H E Lebovitz
Journal: Journal of Clinical Investigation (1982)

We studied the effect of triiodothyronine (T3) on mammalian growth-plate cartilage in vitro. Growth-plate cartilages from fetal pigs scapulae were incubated for 3 to 7 d in serum-free medium alone or medium containing T3. Alkaline phosphatase activity, a marker of hypertrophied chondrocytes, was increased in T3 (10 nM)-treated growth-plate cartilage 152 +/- 36% above that of cartilage incubated in medium alone after 3 d of incubation, and 324 +/- 47% after 7 d of incubation. There was a dose-response increase in alkaline phosphatase activity to T3 over the range of 0.01-10 nM. The rise in alkaline phosphatase activity was specific for T3 since growth-plate cartilage alkaline phosphatase activity was not increased by cortisol, insulin, parathyroid hormone, or 5% fetal calf serum. Histological studies of growth-plate cartilage showed that T3 in a concentration-dependent manner increased the width of the zone of maturation (hypertrophied chondrocytes). Histochemical staining for alkaline phosphatase activity demonstrated that T3 caused the recruitment of new cells into the zone of maturation. T3 also stimulated incorporation of L-[3H]leucine into protein and 35SO4 into proteoglycan in growth-plate cartilage. In contrast, T3 did not increase alkaline phosphatase activity or radiolabeled precursor incorporation into nongrowth-plate scapular cartilage. These studies demonstrate that T3 directly stimulates maturation and, to a lesser degree, growth-related processes in fetal mammalian growth-plate cartilage.
NR4A1 (Nur77) Deletion Polarizes Macrophages Toward an Inflammatory Phenotype and Increases Atherosclerosis
Authors: Richard N. Hanna, Iftach Shaked, Harper G. Hubbeling, Jennifer A. Punt, Runpei Wu, Erica Herrley, Claudia Zaugg, Hong Pei, Frederic Geissmann, Klaus Ley, Catherine C. Hedrick
Journal: Circulation Research (2011)

NR4A1 (Nur77) is a nuclear receptor that is expressed in macrophages and within atherosclerotic lesions, yet its function in atherosclerosis is unknown.Nur77 regulates the development of monocytes, particularly patrolling Ly6C(-) monocytes that may be involved in resolution of inflammation. We sought to determine how absence of nuclear receptor subfamily 4, group A, member 1 (NR4A1) in hematopoietic cells affected atherosclerosis development.Nur77(-/-) chimeric mice on a Ldlr(-/-) background showed a 3-fold increase in atherosclerosis development when fed a Western diet for 20 weeks, despite having a drastic reduction in Ly6C(-) patrolling monocytes. In a second model, mice deficient in both Nur77 and ApoE (ApoE(-/-)Nur77(-/-)) also showed increased atherosclerosis after 11 weeks of Western diet. Atherosclerosis was associated with a significant change in macrophage polarization toward a proinflammatory phenotype, with high expression of tumor necrosis factor-α and nitric oxide and low expression of Arginase-I. Moreover, we found increased expression of toll-like receptor 4 mRNA and protein in Nur77(-/-) macrophages as well as increased phosphorylation of the p65 subunit of NFκB. Inhibition of NFκB activity blocked excess activation of Nur77(-/-) macrophages.We conclude that the absence of Nur77 in monocytes and macrophages results in enhanced toll-like receptor signaling and polarization of macrophages toward a proinflammatory M1 phenotype. Despite having fewer monocytes, Nur77(-/-) mice developed significant atherosclerosis when fed a Western diet. These studies indicate that Nur77 is a novel target for modulating the inflammatory phenotype of monocytes and macrophages and may be important for regulation of atherogenesis.
Novel EBP gene mutations in Conradi–Hünermann–Happle syndrome
Authors: P.M. Steijlen, M. van Geel, M. Vreeburg, D. Marcus-Soekarman, L.J.M. Spaapen, F.C.M. Castelijns, M. Willemsen, M.A.M. van Steensel
Journal: British Journal of Dermatology (2007)

Conradi-Hünermann-Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype.To describe new mutations in patients with variable manifestations of the disease.We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography-mass spectroscopy on serum of two patients.We found two novel (3G-->T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient.The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation.
Thinking and believing in self-deception
Authors: Kent Bach
Journal: Behavioral and Brain Sciences (1997)

Mele views self-deception as belief sustained by motivationally biased treatment of evidence. This view overlooks something essential, for it does not reckon with the fact that in self-deception the truth is dangerously close at hand and must be repeatedly suppressed. Self-deception is not so much a matter of what one positively believes as what one manages not to think.
Acute renal hemodynamic and cardiac hemodynamic effects of endogenous adenosine accumulation in chronic heart failure
Authors: M. Ravani, P. Bertolaccini, C. Palmieri, R. Bonini, F. Paoli, E. Picano, G. Trianni, A. Rizza, S. Berti, A. Maneschi, A. Biagini
Journal: European Journal of Heart Failure (2000)
Secondary induction of cytotoxic T lymphocytes with solubilized syngeneic tumor cell plasma membranes.
Authors: O Alaba, L W Law
Journal: The Journal of Experimental Medicine (1978)

Secondary induction of in vitro cytotoxic T lymphocytes in a syngeneic system has been achieved with plasma membrane, both in the particulate and solubilized forms. Both the induction and the lytic phases were shown to be immunologically specific. The effector cells generated were completely susceptible to treatment with anti-theta antibody and complement, suggesting that they are T lymphocytes.
Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis
Authors: Denuja Karunakaran, A. Brianne Thrush, My-Anh Nguyen, Laura Richards, Michele Geoffrion, Ragunath Singaravelu, Eleni Ramphos, Prakriti Shangari, Mireille Ouimet, John P. Pezacki, Kathryn J. Moore, Ljubica Perisic, Lars Maegdefessel, Ulf Hedin, Mary-Ellen Harper, Katey J. Rayner
Journal: Circulation Research (2015)

Rationale: Therapeutically targeting macrophage reverse cholesterol transport is a promising approach to treat atherosclerosis. Macrophage energy metabolism can significantly influence macrophage phenotype, but how this is controlled in foam cells is not known. Bioinformatic pathway analysis predicts that miR-33 represses a cluster of genes controlling cellular energy metabolism that may be important in macrophage cholesterol efflux. Objective: We hypothesized that cellular energy status can influence cholesterol efflux from macrophages, and that miR-33 reduces cholesterol efflux via repression of mitochondrial energy metabolism pathways. Methods and Results: In this study, we demonstrated that macrophage cholesterol efflux is regulated by mitochondrial ATP production, and that miR-33 controls a network of genes that synchronize mitochondrial function. Inhibition of mitochondrial ATP synthase markedly reduces macrophage cholesterol efflux capacity, and anti-miR33 required fully functional mitochondria to enhance ABCA1-mediated cholesterol efflux. Specifically, anti-miR33 derepressed the novel target genes PGC-1α, PDK4, and SLC25A25 and boosted mitochondrial respiration and production of ATP. Treatment of atherosclerotic Apoe −/− mice with anti-miR33 oligonucleotides reduced aortic sinus lesion area compared with controls, despite no changes in high-density lipoprotein cholesterol or other circulating lipids. Expression of miR-33a/b was markedly increased in human carotid atherosclerotic plaques compared with normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1α, SLC25A25, NRF1, and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans. Conclusions: This study demonstrates that anti-miR33 therapy derepresses genes that enhance mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis.
Hypersensitivity to mugwort (Artemisia vulgaris) in patients with peach allergy is due to a common lipid transfer protein allergen and is often without clinical expression
Authors: Elide A Pastorello, Valerio Pravettoni, Laura Farioli, Federica Rivolta, Amedeo Conti, Marco Ispano, Donatella Fortunato, Anders Bengtsson, Matilde Bianchi
Journal: Journal of Allergy and Clinical Immunology (2002)
Contemporary Use of Ventricular Assist Devices
Authors: Cesare M. Terracciano, Leslie W. Miller, Magdi H. Yacoub
Journal: Annual Review of Medicine (2010)

The introduction of the heart lung machine more than 50 years ago proved in principle that heart function can be replaced, albeit for short periods. This was followed by attempts to produce total or partial artificial hearts that could function for prolonged periods of time. Progress in this field has been intermittent but has accelerated considerably in the past 10 years, with ventricular assist devices (VADs) reaching an impressive degree of sophistication and complexity owing to the contributions from clinicians, engineers, scientists, industrialists, and others. This review describes the currently available types of VADs, their current clinical use, the patient selection process, the trend toward use of VADs in patients with less severe heart failure, and the use of VADs for myocardial recovery in combination with novel pharmacological strategies, gene therapy, and cell therapy.
End-of-Life Care Intensity Among Adolescent and Young Adult Patients With Cancer in Kaiser Permanente Southern California
Authors: Jennifer W. Mack, Lie H. Chen, Kimberley Cannavale, Olivia Sattayapiwat, Robert M. Cooper, Chun R. Chao
Journal: JAMA Oncology (2015)

Cancer is the leading disease-related cause of death among adolescents and young adults (AYAs), but little is known about the care that AYA patients with cancer receive at the end of life (EOL).
Coronary Calcification and the Risk of Heart Failure in the Elderly
Authors: Maarten J.G. Leening, Suzette E. Elias-Smale, Maryam Kavousi, Janine F. Felix, Jaap W. Deckers, Rozemarijn Vliegenthart, Matthijs Oudkerk, Albert Hofman, Ewout W. Steyerberg, Bruno H. Ch. Stricker, Jacqueline C.M. Witteman
Journal: JACC. Cardiovascular imaging (2012)
Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements
Authors: Shaji Kumar, Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Colin Colby, Kristina Laumann, Steve R. Zeldenrust, Nelson Leung, David Dingli, Philip R. Greipp, John A. Lust, Stephen J. Russell, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz
Journal: Journal of Clinical Oncology (2012)

Purpose Cardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro–B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification. Patients and Methods We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials. Results We examined the prognostic value of plasma cell–related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and β 2 microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff ≥ 18 mg/dL, cTnT ≥ 0.025 ng/mL, and NT-ProBNP ≥ 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P &lt; .001). This classification system was validated in the other datasets. Conclusion Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis.