tbuckley/cabot-search huggingface dataset:
Points from letters: Chemotherapy for osteosarcoma
Authors: K W Beetham
Journal: BMJ (1977)

Phosphorylation of the nervous system-specific growth cone protein GAP- 43 by kinase C in vivo occurs exclusively in growth cones and distal axons, and the onset of this phosphorylation is delayed relative to the onset of axonogenesis, with the delay predicted on the time needed for axons to reach the vicinity of their targets (Meiri et al., 1991). We have used a subcellular fraction of intact growth cones (IGCs) to investigate whether this induction of GAP-43 phosphorylation can be influenced by target-derived substances, and show here that increased phosphorylation of GAP-43 can be both stimulated and maintained by NGF at concentrations of 2 x 10(-10) M. This low concentration of NGF and the subsequent phosphorylation of GAP-43 are both consistent with the interpretation that phosphorylation is due to the binding of NGF to a biologically active high-affinity receptor. Second, we used the monoclonal antibody 2G12 to show that the NGF-stimulated phosphorylation of GAP-43 occurs on serine, the kinase C phosphorylation site, consistent with the results seen in vivo. Levels of phosphorylated GAP-43 in the intact IGCs are also modulated by calcium-stimulated dephosphorylation that could be inhibited by EGTA but not okadaic acid and that therefore resembled the calcineurin- stimulated dephosphorylation reported in vitro. The results suggest that the spatial and temporal regulation of GAP-43 phosphorylation that occurs during axonogenesis in vivo can be regulated by target-derived neurotropic molecules, specifically NGF.
A2.19 The Role of microRNA 155 in Innate Immunity and Arthritis
Authors: Victoria Saferding, Eliana Goncalves-Alves, Antonia Puchner, Josef Smolen, Kurt Redlich, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2013)

Background MicroRNA 155 (miR155) has been demonstrated to be essential for the development of collagen induced arthritis by controlling the generation of autoreactive T and B cells. However, the contribution of miR155 in innate immune cells is not known. Materials and Methods We analysed activation and cytokine production of macrophages and dendritic cells (DCs) in vitro and in vivo. We analysed T-cells stimulatory capacity of DCs. We crossed miR155 deficient mice into hTNFtg mice and analysed arthritis development clinically as well as histologically. Results MiR155 deficiency did not alter the expression of costimulatory molecules or MHCII expression after stimulation of macrophages and DCs in vitro and in vivo. We also Facs-sorted DCs after stimulation with LPS in vivo and determined the production of proinflammatory cytokines such as IL-23, IL-6 as well as TNF. We did not detect differences between wt and miR155-/- mice. In addition, the T cell stimulatory capacity of wt and miR155 -/- was identical. When we analysed hTNFtg/miR155 -/- mice compared to wt mice, we did not detect differences in the clinical signs and symptoms of arthritis. Histologically, we even found slightly increased synovial inflammation in hTNFtg/miR155-/- mice compared to wt mice. Conclusions In contrast to the pivotal role of miR155 in autoimmunity requiring the adaptive immune system, the role of miR155 in innate immunity seems to be limited. This is emphasised by the fact that miR155 hardly influences the course of TNF-driven arthritis, which is mainly dependent on components of the innate immune system.
Increased CD74 expression in human atherosclerotic plaques: contribution to inflammatory responses in vascular cells
Authors: J. L. Martin-Ventura, J. Madrigal-Matute, B. Munoz-Garcia, L. M. Blanco-Colio, M. Van Oostrom, G. Zalba, A. Fortuno, C. Gomez-Guerrero, L. Ortega, A. Ortiz, J. Diez, J. Egido
Journal: Cardiovascular Research (2009)

The purpose of this study was to analyse the expression of CD74 in human atherosclerotic plaques and peripheral blood mononuclear cells (PBMC) as well as its potential participation in proinflammatory responses in cultured human vascular smooth muscle cells (VSMC).CD74 expression was analysed in human atherosclerotic plaques (immunohistochemistry), PBMC (real-time PCR), and human aortic VSMC (real-time PCR and western blotting). Nuclear factor-kappaB (NF-kappaB) activation was assessed by southwestern histochemistry and electrophoretic mobility shift assay. Monocyte chemoattractant protein-1 (MCP-1) levels were studied by both real-time PCR and enzyme-linked immunosorbent assay. CD74 immunostaining was increased in the inflammatory vs. the fibrous region of atherosclerotic plaques (n = 70, 18.2 +/- 1.3 vs. 7.8 +/- 0.6% positive staining/mm2, P < 0.001). CD74 colocalized with the transcription factor NF-kappaB in both VSMC and macrophages. In cultured VSMC, CD74 expression was induced by interferon gamma (IFNgamma). Incubation with an agonistic anti-CD74 antibody or with IFNgamma elicited MCP-1 expression, which was prevented by AKT and gamma-secretase inhibitors. Moreover, CD74 small-interfering RNA decreased NF-kappaB activation and MCP-1 production induced by IFNgamma in VSMC. Finally, CD74 mRNA levels in PBMC from patients with carotid stenosis were higher than in healthy subjects (n = 20, 3 +/- 0.5 vs. 2 +/- 0.5 AU, P < 0.001). Additionally, a linear trend between CD74 mRNA expression tertiles and intima-media thickness (IMT) was observed in PBMC from asymptomatic subjects (n = 185, P < 0.001).CD74 levels are increased in plaques and PBMC from patients with carotid stenosis and are associated with IMT in subjects free from clinical cardiovascular diseases. CD74 could be a novel therapeutic target to decrease the inflammatory response in atherosclerosis.
Palmar fasciitis and arthritis in a patient with an extraovarian adenocarcinoma of the coelomic epithelium.
Authors: P H Willemse, N H Mulder, H J van de Tempel, J G Aalders, D T Sleijfer
Journal: Annals of the Rheumatic Diseases (1991)

A 54 year old woman presented with an intra-abdominal adenocarcinoma of primary coelomic origin and a syndrome of palmar fasciitis and arthritis, which was exacerbated during treatment by combination chemotherapy with intravenous carboplatin 300 mg/m2 and cyclophosphamide 750 mg/m2, while the tumour responded well.
Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease
Authors: Aleksandar Videnovic, Charleston Noble, Kathryn J. Reid, Jie Peng, Fred W. Turek, Angelica Marconi, Alfred W. Rademaker, Tanya Simuni, Cindy Zadikoff, Phyllis C. Zee
Journal: JAMA Neurology (2014)

Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD.To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics.A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University.Twenty-four hour monitoring of serum melatonin secretion.Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm.Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm.Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.
Intensive insulin therapy did not reduce mortality more than conventional therapy in septic shock treated with corticosteroids
Authors: Katherine J. Deans
Journal: Annals of Internal Medicine (2010)

Source Citation COIITSS Study Investigators, Annane D, Cariou A, et al. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010;303:341-8. 20103758
CONTRIBUTION OF EXPIRATORY MUSCLE PRESSURE TO DYNAMIC INTRINSIC POSITIVE END-EXPIRATORY PRESSURE
Authors: Spyros G. Zakynthinos, Theodoros Vassilakopoulos
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In spontaneously breathing (SB) patients expiratory muscle contraction leads to an overestimation of dynamic intrinsic PEEP (PEEPi,dyn). To quantify this overestimation, PEEPi,dyn measured with the esophageal balloon technique was corrected for the increase in Pga over the course of expiration (Pga,exp rise), for the whole decay of Pga during inspiration (Pga,total decay) or for the part of Pga decay restricted between the onset of inspiratory effort and the point of zero flow (Pga,zf decay). Corrections were compared with the reference PEEPi,dyn (PEEPi,dyn ref ), calculated by using the Campbell diagram. In 15 ventilator-dependent, SB, and actively expiring patients, we found that the difference PEEPi,dyn − Pga,total decay (mean ± SD, 5.7 ± 1.9 cm H2O) was quite similar to PEEPi,dyn ref (5.3 ± 1.9 cm H2O). Their mean difference was 0.37 cm H2O with limits of agreement − 0.09 to 0.83 cm H2O, indicating strong agreement between these methods. PEEPi,dyn − Pga,exp rise (6.0 ± 2.1 cm H2O) was also similar to ...
The Discovery of the Unconscious: The History and Evolution of Dynamic Psychiatry
Authors: Marjorie C. Meehan
Journal: JAMA (1970)

This is a fascinating history of one of the most important scientific developments of the past two centuries—dynamic psychiatry. Although much of the material is familiar, almost everyone will find new information and new facts here. Professor Ellenberger has done a tremendous amount of research, combining material from philosophy, literature, social history, and many other fields to explain the growth of psychological understanding.  The first third of the book describes the 18th- and 19th-century background. Here we read about exorcists, magnetizers, hypnotists, philosophers, psychological experimenters, investigators of dreams. We see the continuing influences of the thought of successive eras—the Renaissance, the Baroque, and especially the Enlightenment and Romantic period.  Four long chapters on Janet, Freud, Adler, and Jung constitute the main body of the book. Here are excellent summaries of the life and work of each. Janet, who did not establish a school, had little or no contact with the
Response of human chondrocytes to a non-uniform distribution of hydrophilic domains on poly (ethyl acrylate-co-hydroxyethyl methacrylate) copolymers
Authors: Marcos Pérez Olmedilla, Natalia Garcia-Giralt, Manuel Monleón Pradas, Pere Benito Ruiz, José Luis Gómez Ribelles, Enric Cáceres Palou, Joan Carles Monllau García
Journal: Biomaterials (2005)
Mechanical and structural correlates of contracture induced by metabolic blockade in cardiac muscle from the rat.
Authors: O H Bing, M C Fishbein
Journal: Circulation Research (1979)

We performed morphological studies of myocardial contracture to define its nature and relationship to mechanical changes occurring during metabolic blockade. Isolated rat papillary and trabecular muscles were stretched to the apices of their length-tension curves and stimulated to contract isometrically 12 times a minute at a temperature of 28 degrees C. Incomplete and total metabolic blockade were induced by 1 hour of hypoxia (95% N2, 5% CO2) or by hypoxia plus glycolytic blockade with iodoacetic acid, 10-4M, respectively. In oxygenated control preparations, mechanical performance was stable for the 60-minute experimental period. In preparations exposed to hypoxia, developed tension fell to 7 +/- 2% of prehypoxia values at 60 minutes. Contracture tension increased progressively to 2.5 +/- 0.4 g/mm2. With total metabolic blockade, developed tension declined to zero by 10 minutes, contracture tension rose to an average peak value of 5.3 +/- 0.4 g/mm2 by 15 minutes, and subsequently slowly declined. All preparations were fixed at Lmax in the muscle bath. Light and electron microscopic studies revealed focal irregularities of A, I, and Z bands with sarcomere malalignment, hypercontraction, and fiber disruption, which increased in severity with increasing metabolic blockade. Linear densities appeared in mitochondria following total metabolic blockade, but mitochondria appeared normal otherwise. Thus, myocardial contracture after metabolic blockade is a focal process beginning within the sarcomere; morphological alterations in the contractile apparatus correlate with mechanical changes and are more severe than those in the mitochondria.
Abstract 4309: Fibulin-2 suppresses tumor growth and angiogenesis through the inhibition of Erk1/2 and p65 pathways in nasopharyngeal carcinoma.
Authors: Wai Ho Shuen, Maria Li Lung
Journal: Cancer Research (2013)

Abstract Nasopharyngeal carcinoma (NPC) has distinctive ethnic and geographic distributions, with the highest incidence in Southern China. Infection with the human herpesvirus, Epstein-Barr virus, genetic predisposition, dietary, and environmental factors are high-risk factors for the development of NPC. Evidence indicates that loss of heterozygosity on chromosome 3 is one of the early events contributing to the cancerization of normal nasopharyngeal epithelial cells. By using a chromosome 3 NotI genomic microarray, Fibulin-2 (FBLN2) mapping to chromosome 3p25.1, was previously identified as a candidate tumor suppressor. FBLN2, which is an extracellular matrix (ECM) protein, contains four domains, regions consisting of cysteine-rich and cysteine-free, anaphylatoxin-like domain, serial EGF-like repeats, and a fibulin module. FBLN2 is silenced by promoter hypermethylation in NPC. Re-expression of FBLN2 in NPC cell lines significantly reduces colony formation, cell proliferation, migration, invasion, and in vivo tumor formation and angiogenesis. In this study, the aim is to investigate the molecular mechanisms and signaling pathways of FBLN2-mediated tumor suppressive and anti-angiogenesis effects. Full-length FBLN2 was subcloned into inducible tetracycline-regulated and lentivirus systems. Phosphorylated forms of the key signaling molecules, Erk1/2 and NFκB, were found to be significantly reduced in FBLN2 stably-expressing NPC cell lines after phosphorylation target screening using Western blot analysis. FBLN2 also induces changes in the cytoskeleton arrangement, possibly through the regulation of Rho GTPases. Thus, the activities of Rho GTPases were determined by the Rho pull-down assays and immunofluorescence staining with confocal microscopy. FBLN2 is able to reduce the tumor formation ability via inhibiting Erk1/2 and NFκB pathways and to inhibit the cell migration and invasion via regulating Rho GTPase activities. FBLN2 is a secretory protein and is generally silenced in NPC, suggesting the possibility that it may be useful as a diagnostic marker and/or new target for therapeutics of NPC. Therefore, these studies provide strategic new insights into the understanding of the mechanistic role of FBLN2 in NPC and enhance our understanding of the molecular genetic basis of NPC tumorigenesis. Citation Format: Wai Ho Shuen, Maria Li Lung. Fibulin-2 suppresses tumor growth and angiogenesis through the inhibition of Erk1/2 and p65 pathways in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4309. doi:10.1158/1538-7445.AM2013-4309
Maximization theory in behavioral psychology
Authors: Howard Rachlin, Ray Battalio, John Kagel, Leonard Green
Journal: Behavioral and Brain Sciences (1981)

Abstract Maximization theory, which is borrowed from economics, provides techniques for predicing the behavior of animals - including humans. A theoretical behavioral space is constructed in which each point represents a given combination of various behavioral alternatives. With two alternatives - behavior A and behavior B - each point within the space represents a certain amount of time spent performing behavior A and a certain amount of time spent performing behavior B. A particular environmental situation can be described as a constraint on available points (a circumscribed area) within the space. Maximization theory assumes that animals always choose the available point with the highest numerical value. The task of maximization theory is to assign to points in the behavioral space values that remain constant across various environmental situations; as those situations change, the point actually chosen is always the one with the highest assigned value. Maximization theory is an alternative to reinforcement theory as a description of steady-state behavior. Situations to which reinforcement theory has been directly applied (such as reinforcement of rats pressing levers and pigeons pecking keys in Skinner boxes) and situations to which reinforcement theory has occasionally been extended (such as human economic behavior and human self-control) can be described by maximization theory. This approach views behavior as a quantitative outcome of the interaction of the putative instrumental response, the reinforcer, and the other activities available in the situation. It provides new insight into these situations and, because it takes context into account, has greater predictive power than reinforcement theory.
Adrenal Cortical Adenoma Causing Gushing??s Syndrome
Authors: O. GEATTI, L. FIG, B. SHAPIRO
Journal: Clinical Nuclear Medicine (1990)

A 60-year-old woman with Cushing's syndrome in whom high-dose dexamethasone failed to suppress glucocorti-coids was studied by ultrasound and CT. Neither of these morphological studies was interpreted as revealing any adrenal abnormality. Functional imaging with NP-59 (131-l-β-iodomethylnorcholesterol) revealed unequivocal, intense, unilateral uptake in the left adrenal gland and subsequent surgery removed a 2.5 cm adrenocortical adenoma from this site. Following surgery the patient was temporarily adrenocortically insufficient but later returned to normal. It is unusual for adrenocortical adenomas causing Cushing's syndrome not to be correctly located by CT. NP-59 scintigraphy in addition to being highly accurate in the location of adrenocortical adenomas also has the advantage of correctly depicting bilateral cortical nodular hyperplasia in which CT will frequently reveal only the largest nodule, which may be incorrectly designated a unilateral adenoma. Furthermore, scintigraphy provides evidence of suppression of the contralateral, normal adrenal cortical tissue in Cushing's syndrome caused by an adrenal adenoma and predicts the vulnerability of such patients to postoperative adrenocortical insufficiency.
Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia
Authors: Ruth Pidsley, Joana Viana, Eilis Hannon, Helen Spiers, Claire Troakes, Safa Al-Saraj, Naguib Mechawar, Gustavo Turecki, Leonard C Schalkwyk, Nicholas J Bray, Jonathan Mill
Journal: Genome biology (2014)

Abstract Background Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development. There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that schizophrenia-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.
The Role of Radiation Therapy in Carcinoma of the Lung
Authors: Donald R. Eisert
Journal: JAMA (1982)

IN 1977, cancer of the lung was the most frequent cause of death from cancer in the United States. It is estimated that 122,000 new cases of cancer of the lung and 105,000 deaths from the disease will occur in 1981. While cancer of the lung is the most frequent malignant tumor in men in the United States, the incidence in women is rapidly increasing. Since 1950, both sexes have experienced a threefold increase.<sup>1</sup> Fifty percent of all patients with bronchogenic carcinoma are inoperable when the diagnosis is established. Of the remaining 50%, only one half, or 25% of the initial population, is resectable. While surgery remains the treatment of choice for resectable carcinomas (with the exception of small cell undifferentiated tumors), patients who are not surgical candidates, for medical or technical reasons, should be considered for radiation therapy delivered with curative intent. In addition to radical radiation therapy,
Regression of Low-Grade Non-Hodgkin's Lymphoma After Treatment With Pegylated Interferon Plus Ribavirin in Hepatitis C Virus Infection
Authors: Cesare Mazzaro, Michele Spina, Umberto Tirelli
Journal: Journal of Clinical Oncology (2005)

breast cancer (n ϭ 65), and normal breast reduction tissue (n ϭ 60).They found that COX-2 expression in DCIS (67%; P Ͻ .001) and in invasive breast cancer (63%; P Ͻ .001) was significantly greater than COX-2 expression in normal breast tissue (23%).In DCIS, COX-2 expression was also associated with higher cellular proliferation rates (P Ͻ .0001)and nuclear grade (P ϭ .003),with ER negativity (P ϭ .003),and with HER-2 positivity (P Ͻ .0001).Eighty percent of ER-negative DCIS tumors showed COX-2 positivity, compared with 58% of ER-positive DCIS tumors (P ϭ .003).These findings, together with the association of COX-2 with HER-2 expression, are important because these factors are surrogate markers of an aggressive DCIS phenotype and link nonestrogen growth factor-signaling pathways with COX-2 overexpression.Therefore, COX-2 inhibitors and trastuzumab may have a role in preventing invasive breast cancer in patients with ER-negative DCIS.