tbuckley/cabot-search huggingface dataset:
Emotion Circuits in the Brain
Authors: Joseph E. LeDoux
Journal: Annual Review of Neuroscience (2000)

The field of neuroscience has, after a long period of looking the other way, again embraced emotion as an important research area. Much of the progress has come from studies of fear, and especially fear conditioning. This work has pinpointed the amygdala as an important component of the system involved in the acquisition, storage, and expression of fear memory and has elucidated in detail how stimuli enter, travel through, and exit the amygdala. Some progress has also been made in understanding the cellular and molecular mechanisms that underlie fear conditioning, and recent studies have also shown that the findings from experimental animals apply to the human brain. It is important to remember why this work on emotion succeeded where past efforts failed. It focused on a psychologically well-defined aspect of emotion, avoided vague and poorly defined concepts such as “affect,” “hedonic tone,” or “emotional feelings,” and used a simple and straightforward experimental approach. With so much research being done in this area today, it is important that the mistakes of the past not be made again. It is also time to expand from this foundation into broader aspects of mind and behavior
Measurement of bronchial elastance in resected sheep lungs
Authors: A. J. Akhtar, S. Merchant, G. J. R. McHardy, J. W. Crofton
Journal: Thorax (1973)

The elastance of bronchial segments in resected sheep lungs has been measured by the following method. A balloon mounted on a probe was introduced into a bronchus of 3-4 mm diameter, the elastance of the balloon itself having been determined previously. The changes in pressure in the balloon resulting from the addition of successive small volumes of saline to the balloon were recorded, and the slope of the resulting pressure/volume curve gave the elastance of balloon and bronchus. The bronchial elastance was found by subtracting the elastance of the balloon from the combined value. Estimates of bronchial elastance derived from repeated inflations of the balloon during a single insertion showed little variation. Considerable variation was found between bronchi in the same animal and between animals, the elastance ranging from 1·1 to 3·4 cm H<sub>2</sub>O/μ1 in the 25 bronchi studied. Repeated insertion of the balloon into the same bronchus was accompanied by a progressive increase in elastance; possible causes for this are discussed. It is hoped that the method may be applicable in man.
A Norwegian Psychiatric Epidemiological Study
Authors: E Kringlen, S Torgersen, V Cramer
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study reports results of a large-scale epidemiological investigation of the prevalence of mental disorder in Oslo. METHOD: A random sample of Oslo residents age 18–65 years was drawn from the Norwegian National Population Register. A total of 2,066 subjects, 57.5% of the original sample, were interviewed with the Composite International Diagnostic Interview in 1994–1997. The mean age of the interviewed subjects was 39.3 years. RESULTS: The 12-month prevalence of all mental disorders was 32.8%, and the lifetime prevalence was 52.4%. Alcohol abuse/dependence and major depression had the highest lifetime prevalence and 12-month prevalences. All mental disorders were more prevalent in women than in men, with the exception of alcohol and drug abuse/dependence. Severe psychopathology (e.g., three or more diagnoses) was found in 14%–15% of the respondents. The lifetime and 12-month prevalences for all diagnostic categories except drug abuse/dependence were similar to those found in the United States Comorbidity Survey. CONCLUSIONS: Epidemiological data for Oslo show that the lifetime and 12-month prevalences of mental disorder are quite high, with alcohol abuse/dependence and major depression particularly frequent. The rates for women are higher than those for men for all diagnostic categories, except for alcohol and drug abuse/dependence.
Prognostic influence of Barrett's oesophagus and Helicobacter pylori infection on healing of erosive gastro-oesophageal reflux disease (GORD) and symptom resolution in non-erosive GORD: report from the ProGORD study
Authors: P Malfertheiner
Journal: Gut (2005)

<b>Background:</b> Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase. <b>Methods:</b> Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4–8 weeks for endoscopic healing while NERD patients received 20 mg for 2–4 weeks for resolution of heartburn symptoms. <b>Results:</b> Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in <i>Helicobacter pylori</i> negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only <i>H pylori</i> infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for <i>H pylori</i> positive and <i>H pylori</i> negative, respectively; p = 0.03). <b>Conclusion:</b> The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. <i>H pylori</i> infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.
Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.
Authors: R Kiekens, P In 't Veld, T Mahler, F Schuit, M Van De Winkel, D Pipeleers
Journal: Journal of Clinical Investigation (1992)

In vitro incubated rat islet B cells differ in their individual rates of protein synthesis. The number of cells in biosynthetic activity increases with the glucose concentration. Flow cytometric monitoring of the cellular redox states indicated that islet B cells differ in their individual metabolic responsiveness to glucose. A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM. The functional significance of this metabolic heterogeneity was assessed by comparing protein synthesis in metabolically responsive and unresponsive subpopulations, shortly after their separation by autofluorescence-activated cell sorting. The glucose-sensitive subpopulation exhibited four- to fivefold higher rates of insulin synthesis during 60-min incubations at 2.5-10 mM glucose. Its higher biosynthetic activity was mainly caused by recruitment of cells into active synthesis and, to a lesser extent, by higher biosynthetic activity per recruited cell. Cells from the glucose-sensitive subpopulation were larger, and presented a threefold higher density of a pale secretory vesicle subtype, which is thought to contain unprocessed proinsulin. It is concluded that intercellular differences in metabolic responsiveness result in functional heterogeneity of the pancreatic B cell population.
Predicting energy expenditure through hand rim propulsion power output in individuals who use wheelchairs
Authors: Scott A Conger, Stacy N Scott, David R Bassett
Journal: British Journal of Sports Medicine (2014)

To examine the relationship between hand rim propulsion power and energy expenditure (EE) during wheelchair wheeling and to investigate whether adding other variables to the model could improve on the prediction of EE.Individuals who use manual wheelchairs (n=14) performed five different wheeling activities in a wheelchair with a PowerTap power meter hub built into the right rear wheel. Activities included wheeling on a smooth, level surface at three different speeds (4.5, 5.5 and 6.5 km/h), wheeling on a rubberised track at one speed (5.5 km/h) and wheeling on a sidewalk course that included uphill and downhill segments at a self-selected speed. EE was measured using a portable indirect calorimetry system. Stepwise linear regression was performed to predict EE from power output variables. A repeated-measures analysis of variance was used to compare the measured EE to the estimates from the power models. Bland-Altman plots were used to assess the agreement between the criterion values and the predicted values.EE and power were significantly correlated (r=0.694, p<0.001). Regression analysis yielded three significant prediction models utilising measured power; measured power and speed; and measured power, speed and heart rate. No significant differences were found between measured EE and any of the prediction models.EE can be accurately and precisely estimated based on hand rim propulsion power. These results indicate that power could be used as a method to assess EE in individuals who use wheelchairs.
The New Soviet Approach to the Unconscious
Authors: NANCY ROLLINS
Journal: American Journal of Psychiatry (1974)

Soviet investigators have moved from criticism of psychoanalytic concepts to development of a theory of the unconscious that represents the convergence of set theory, neurophysiology, and cybernetics. One accepted Soviet definition of the unconscious is the continuous processing of information and the regulation of adaptive behavior through the formation of sets. Consciousness operates intermittently, when a problem must be solved by objectivization, with a change in sets. Conscious and unconscious processes act synergistically, not antagonistically, as Freud suggested. Dissociation, psychosomatic relationships, and psychotherapy are briefly discussed to illustrate the Soviet approach to the unconscious in psychiatry.
A non-invasive technique to genotype lung cancer cells
Authors: A Cheong
Journal: Thorax (2009)

Mutations in the epithelial growth factor receptor (EGFR) are thought to occur early in the oncogenesis of non-small cell lung carcinoma (NSCLC). This paper describes the use of a novel chip to capture circulating tumour cells (CTCs) combined with a “SARMS” (Scorpion Amplification Refractory Mutation System) allele-specific genotyping assay to detect EGFR mutations.

The study …
Class IV Semaphorins Promote Angiogenesis by Stimulating Rho-Initiated Pathways through Plexin-B
Authors: John R. Basile, Ana Barac, Tianqing Zhu, Kun-Liang Guan, J. Silvio Gutkind
Journal: Cancer Research (2004)

Abstract The semaphorins are a large family of secreted and cell surface proteins that provide attractive and repulsive cues for axon guidance during neuronal development. Semaphorins share a conserved NH2-terminal Sema domain with their receptors, the plexins, which mediate neuronal cell adhesion, axon guidance, and maintenance of established neuronal pathways in the adult. Both semaphorins and plexins share structural homology with the extracellular domain of c-Met, a member of the scatter factor family of receptors. However, the highly conserved cytoplasmic region of plexins has no homology with the c-Met tyrosine kinase or with any other known protein. Using a recently developed antibody and RNA analysis, we found that high levels of plexin-B1 are expressed in endothelial cells. Whereas c-Met, with which plexin-B1 can interact, is known to be a potent promoter of angiogenesis, the effects of semaphorin-mediated plexin activation in endothelial cells are still poorly understood. Here, we examined the role of plexin-B1 activation in angiogenesis using a purified, secreted form of its ligand, Semaphorin 4D (Sema4D). Sema4D potently induced chemotaxis and tubulogenesis in endothelial cells and enhanced blood vessel formation in an in vivo mouse model. Interestingly, responses to Sema4D did not require c-Met activation. Instead, the use of chimeric plexin-B1 receptors, Rho inhibitors, and lentiviral gene delivery of interfering molecules revealed that these proangiogenic effects are dependent on a COOH-terminal PDZ-binding motif of plexin-B1, which binds two guanine nucleotide exchange factors for the small GTPase Rho, PDZ-RhoGEF and LARG, and are mediated by the activation of Rho-initiated pathways.
Modulation of Immunoglobulin (Ig)E-mediated Systemic Anaphylaxis by Low-Affinity Fc Receptors for IgG
Authors: Azusa Ujike, Yoko Ishikawa, Masao Ono, Takae Yuasa, Tadashi Yoshino, Manabu Fukumoto, Jeffrey V. Ravetch, Toshiyuki Takai
Journal: The Journal of Experimental Medicine (1999)

It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FcεRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc receptors for IgG, FcγRII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in FcγR-deficient mice. Mice deficient in the inhibitory receptor for IgG, FcγRIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, FcγRIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, FcγRII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc receptors that could contribute to the etiology of the atopic response.
Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation
Authors: Marina Bousquet, Cathy Quelen, Roberto Rosati, Véronique Mansat-De Mas, Roberta La Starza, Christian Bastard, Eric Lippert, Pascaline Talmant, Marina Lafage-Pochitaloff, Dominique Leroux, Carine Gervais, Franck Viguié, Jean-Luc Lai, Christine Terre, Berna Beverlo, Costantina Sambani, Anne Hagemeijer, Peter Marynen, Georges Delsol, Nicole Dastugue, Cristina Mecucci, Pierre Brousset
Journal: The Journal of Experimental Medicine (2008)

Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity.
Germline Mutations in the<i>BRCA2</i>Gene and Susceptibility to Hereditary Prostate Cancer
Authors: Ilir Agalliu, Erika M. Kwon, Daniel Zadory, Laura McIntosh, Joseph Thompson, Janet L. Stanford, Elaine A. Ostrander
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Several epidemiologic studies have reported that carriers of germline mutations in the BRCA2 gene have an increased risk of prostate cancer, with the highest risk observed in men diagnosed at earlier ages. However, studies of the contribution of BRCA2 mutations to the etiology of hereditary prostate cancer (HPC) have been inconsistent. Experimental Design: To further address this issue, 266 subjects from 194 HPC families participating in the Seattle-based Prostate Cancer Genetic Research Study were screened for BRCA2 mutations by sequencing the coding regions, intron-exon boundaries, and suspected regulatory elements of this gene. Of selected HPC families, 32 had multiple breast or ovarian cancer cases, 16 were Jewish, 8 had a pancreatic cancer case, and 138 had at least one affected man diagnosed with prostate cancer at an early age (&amp;lt;60 years). Results: No disease-associated protein truncating BRCA2 mutations were found in 266 subjects from HPC families. There were 61 DNA sequence variants, of which 31 (50.8%) changed the predicted amino acids. No associations were found between these missense changes and family characteristics. Among affected men with prostate cancer, there were no statistically significant differences between the genotype frequencies of DNA variants with a minor allele frequency of 1% or higher and between the strata defined by median age at diagnosis or by clinical features. Conclusion: No evidence was found in this study for an association between BRCA2 mutations and susceptibility to HPC in men selected from high-risk families.
High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells.
Authors: M Fujii, K Sugamura, K Sano, M Nakai, K Sugita, Y Hinuma
Journal: The Journal of Experimental Medicine (1986)

Receptor-mediated internalization and degradation of IL-2 were investigated in cell lines carrying human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I) and PHA-treated normal PBL. The HTLV-I-carrying cell lines ILT-Yan and TL-Mor, and the PBL expressed both high- and low-affinity IL-2-R. However, another HTLV-I-carrying T cell line, MT-1, expressed mainly low-affinity receptors. Greater than 50% of the IL-2 bound to high-affinity receptors was internalized within 10 min when these cells were incubated at 37 degrees C. The internalized IL-2 was rapidly degraded and the products were excreted into the culture fluid. The t1/2 of IL-2 degradation in these cells was estimated as 60-80 min at 37 degrees C. The internalization and degradation of IL-2 were both temperature dependent. Light-microscopic autoradiography with 3H-labeled IL-2 confirmed the internalization of IL-2, and suggested that some IL-2 might be carried to the nucleus.
Naturally occurring aliphatic polyamines‐induced histamine release from rat peritoneal mast cells
Authors: M. Kurosawa, D. Uno, S. Kobayashi
Journal: Allergy (1991)

Rat peritoneal mast cells were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1-10 mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose-dependent manner. The effect of 10 mM spermine and spermidine was as much as that of 0.5 microgram/ml compound 48/80. The histamine release from the cells incubated with each polyamine was rapid and the amount of histamine release into the supernatant solutions reached a maximum at 1 min with the incubations. 0.1 mM spermine, which in itself could not cause a significant histamine release, showed a tendency to enhance anti-IgE-induced histamine release from the mast cells.
Defective colony formation by B lymphocytes from CBA/N and C3H/HeJ mice.
Authors: P W Kincade
Journal: The Journal of Experimental Medicine (1977)

B cells from CBA/N mice did not form colonies in semisolid agar cultures under circumstances where normal B-cell clonal proliferation is linear with respect to the number of functional cells cultured. This was no due to the unresponsiveness of CBA/N cells to mitogens, and under appropriate liquid culture conditions many CBA/N lymphocytes differentiated to plasma cells containing large amounts of IgM in response to LPS. On the other hand, the same cells proliferated and matured poorly in liquid cultures prepared at low-cell density. The frequency of granulocyte-macrophage progenitors and multipotential hemopoietic stem cells in bone marrow, ability of peritoneal macrophages to elaborate soluble enhancing factors, and levels of serum inhibitors were normal in CBA/N mice. Together with the results of cell-mixing experiments, these findings confirm the selective and intrinsic nature of the CBA/N deficiency. It is suggested that the B-cell cloning technique may be of value in selectively enumerating and assessing functional capability of thymus-independent B cells. C3H/HeJ mice which have previously only been known to be hyporesponsive to certain forms of lipopolysaccharide had a subnormal incidence of colony-forming B cells.
Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors.
Authors: L C Pronk, J H Schellens, A S Planting, M J van den Bent, P H Hilkens, M E van der Burg, M de Boer-Dennert, J Ma, C Blanc, M Harteveld, R Bruno, G Stoter, J Verweij
Journal: Journal of Clinical Oncology (1997)

PURPOSE This phase I study was performed to assess the feasibility of the combination of docetaxel and cisplatin and to determine the maximum-tolerated dose (MTD) and the side effects with an emphasis on sequence-dependent side effects. MATERIALS AND METHODS Patients who were not pretreated with taxanes or cisplatin derivatives and who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered. Treatment consisted of docetaxel given as a 1-hour infusion followed by cisplatin as a 3-hour infusion (schedule A), or cisplatin followed by docetaxel (schedule B). Docetaxel doses ranged from 55 to 100 mg/m2 and cisplatin doses from 50 to 100 mg/m2. RESULTS Leukocytopenia and granulocytopenia were common (overall, 90%; grade 3 or 4, 87%), short-lasting, and docetaxel dose-dependent. Infections and neutropenic fever occurred in 10% and 4.5% of courses, respectively. Nonhematologic toxicities were mild to moderate and included alopecia, nausea, vomiting, diarrhea, mucositis, neurotoxicity, fluid retention, and skin and nail toxicity. There were no significant differences in pharmacokinetic parameters between schedules A and B. Tumor responses included one complete response (CR) and nine partial responses (PRs). CONCLUSION The dose levels docetaxel 100 mg/m2 plus cisplatin 75 mg/m2 and docetaxel 85 mg/m2 plus cisplatin 100 mg/m2 appeared to be manageable. At these dose levels, the median relative dose-intensity was high and 81% and 88% of all cycles, respectively, could be given at full dose. Schedule A is advocated for further treatment.