tbuckley/cabot-search huggingface dataset:
Life-Threatening Danger and Suppression of Attention Bias to Threat
Authors: Yair Bar-Haim, Yael Holoshitz, Sharon Eldar, Tahl I. Frenkel, David Muller, Dennis S. Charney, Daniel S. Pine, Nathan A. Fox, Ilan Wald
Journal: American Journal of Psychiatry (2010)

Life-threatening danger is assumed to produce, in tandem, increases in both vigilance toward threat and stress-related symptoms, but no data test the validity of this assumption. The authors examined associations, in real time, among imminent life-threatening danger, stress-related symptoms, and vigilance.Symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety were measured in a civilian population (N=131) as a function of war-related stress, operationalized as the time available for seeking cover from rocket attack. A computerized measure of threat-related vigilance using a classic dot-probe attention task was also collected.PTSD symptoms, depression, and anxiety increased as a function of war-related threat. Acute proximal threat was associated with avoidance of, rather than vigilance toward, negative valence information. For participants within rocket range, the magnitude of threat bias varied with the magnitude of distress symptoms, such that as bias away from threat increased, distress symptoms increased.These data challenge current thinking about the role of attention in stress responding. Attentional threat avoidance may reduce the acute impact of imminent threat, but this may come at a price in terms of an elevated risk for psychopathology.
The promotion of osteoclastogenesis by sulfated hyaluronan through interference with osteoprotegerin and receptor activator of NF-κB ligand/osteoprotegerin complex formation
Authors: Juliane Salbach-Hirsch, Julia Kraemer, Martina Rauner, Sergey A. Samsonov, M. Teresa Pisabarro, Stephanie Moeller, Matthias Schnabelrauch, Dieter Scharnweber, Lorenz C. Hofbauer, Vera Hintze
Journal: Biomaterials (2013)
Stem Cell Factor Induction Is Associated With Mast Cell Accumulation After Canine Myocardial Ischemia and Reperfusion
Authors: Nikolaos G. Frangogiannis, Jerry L. Perrard, Leonardo H. Mendoza, Alan R. Burns, Merry L. Lindsey, Christie M. Ballantyne, Lloyd H. Michael, C. Wayne Smith, Mark L. Entman
Journal: Circulation (1998)

Background —Myocardial infarction is associated with an intense inflammatory reaction leading to healing and scar formation. Because mast cells are a significant source of fibrogenic factors, we investigated mast cell accumulation and regulation of stem cell factor (SCF), a potent growth and tactic factor for mast cells, in the healing myocardium. Methods and Results —Using a canine model of myocardial ischemia and reperfusion, we demonstrated a striking increase of mast cell numbers during the healing phase of a myocardial infarction. Mast cell numbers started increasing after 72 hours of reperfusion, showing maximum accumulation in areas of collagen deposition (12.0±2.6-fold increase; P &lt;0.01) and proliferating cell nuclear antigen (PCNA) expression. The majority of proliferating cells were identified as α-smooth muscle actin–positive myofibroblasts or factor VIII–positive endothelial cells. Mast cells did not appear to proliferate. Using a nuclease protection assay, we demonstrated induction of SCF mRNA within 72 hours of reperfusion. Immunohistochemical studies demonstrated that a subset of macrophages was the source of SCF immunoreactivity in the infarcted myocardium. SCF protein was not found in endothelial cells and myofibroblasts. Intravascular tryptase–positive, FITC-avidin–positive, CD11b-negative mast cell precursors were noted in the area of healing and in the cardiac lymph after 48 to 72 hours of reperfusion. Conclusions —Mast cells increase in number in areas of collagen deposition and PCNA expression after myocardial ischemia. The data provide evidence of mast cell precursor infiltration into the areas of cellular injury. SCF is induced in a subset of macrophages infiltrating the healing myocardium. We suggest an important role for SCF in promoting chemotaxis and growth of mast cell precursors in the healing heart.
Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study
Authors: Janie F. Shelton, Estella M. Geraghty, Daniel J. Tancredi, Lora D. Delwiche, Rebecca J. Schmidt, Beate Ritz, Robin L. Hansen, Irva Hertz-Picciotto
Journal: Environmental Health Perspectives (2014)

Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study.The CHARGE study is a population-based case-control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.
Abstract 2750: ARQ 621, a novel potent and selective inhibitor of Eg5: Preclinical data and early results from a clinical phase 1 study
Authors: Lee Rosen, Lin-Chi Chen, Tara Iyengar, Jonathan Goldman, Sandra Lahr, Chang-rung Chen, Dennis S. France, Thomas C.K. Chan, Brian Schwartz, Giovanni Abbadessa, Daniel D. Von Hoff
Journal: Cancer Research (2010)

Abstract Background: ARQ 621 is an allosteric, potent and selective inhibitor of Eg5, a microtubule-based ATPase motor protein involved in cell division. Eg5 inhibition is recognized as a potential therapeutic strategy in cancer supported by the observation that over-expression of Eg5 causes genomic instability and tumor formation in mice. In this clinical trial we sought to evaluate the safety and pharmacokinetics of ARQ 621 in patients with solid tumors. Methods: Patients (pts) are being enrolled into this multi-cohort phase 1 trial at the initial i.v. dose of 10 mg/m2/week. Drug is administered weekly intravenously over 1-2 hours. Cohorts of 3 or 6 patients are based on a 3+3 dose escalation schedule and dose is increased according to a modified Fibonacci scheme. Treatment continues until disease progression or unacceptable toxicity. Results: Recently expanded preclinical data with ARQ 621 shows anti-tumor activity with potencies in the low nanomolar range across a much wider range of human cancer cell types than previously reported, including colon, NSCLC, gastric, and hematologic cancer cell lines. Furthermore, no evidence of bone marrow toxicity and DNA damage is evident with ARQ 621 as we have seen with a leading Eg5 inhibitor. As of November 19, 2009, 18 pts (60% male; median age 60 yrs, ECOG PS 0 (N=3), PS 1 (N=13), PS 2 (N=2) were enrolled. The most common tumors treated with ARQ 621 were colorectal (N=6) and breast (N=2). Treatment-emergent adverse events (TEAEs) were reported in 13 pts. The most common (&amp;gt; 10%) include fatigue (27%), redness at infusion site 3 (16%), and anemia 3 (16%). Three pts experienced serious AEs (1 each of anemia, sepsis, pneumonia) reported as not drug related. Three pts (cholangiosarcoma, liposarcoma and colorectal carcinoma) remained stable for &amp;gt; 4 months. Conclusions: Preclinical studies continue to elucidate the potential indications for Eg5 inhibition as well as the combinability of ARQ 621 with other molecularly targeted therapeutics. To date, therapy with ARQ 621 appears well tolerated, with no dose-limiting toxicity observed at doses and frequencies much higher than those achieved with the leading Eg5 inhibitors of comparable potencies. Dose-limiting toxicity has not been reached, and recruitment continues to identify the maximum tolerated dose and a recommended Phase 2 dose. Additional safety, pharmacokinetic, and preliminary efficacy data will be available for presentation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2750.
Monophyly of the order Rodentia inferred from mitochondrial DNA sequences of the genes for 12S rRNA, 16S rRNA, and tRNA-valine.
Authors: M. S. Frye, S. B. Hedges
Journal: Molecular Biology and Evolution (1995)

A recent analysis of amino acid sequence data (Graur et al.) suggested that the mammalian order Rodentia is polyphyletic, in contrast to most morphological data, which support rodent monophyly. At issue is whether the hystricognath rodents, such as the guinea pig, represent an independent evolutionary lineage within mammals, separate from the sciurognath rodents. To resolve this problem, we sequenced a region (2,645 bp) of the mitochondrial genome of the guinea pig containing the complete 12S ribosomal RNA, 16S ribosomal RNA, and transfer RNA(VAL) genes for comparison with the available sciurognath and other mammalian sequences. Several methods of analysis and statistical tests of the data all show strong support for rodent monophyly (91%-98% bootstrap probability, or BP). Calibration with the mammalian fossil record suggests a Cretaceous date (107 mya) for the divergence of sciurognaths and hystricognaths. An older date (38 mya) for the controversial Mus-Rattus divergence also is supported by these data. Our neighbor-joining analyses of all available sequence data (25 genes) confirm that some individual genes support rodent polyphyly but that tandem analysis of all data does not. We propose that the conflicting results are due to several compounding factors. The unique biochemical properties of some hystricognath metabolic proteins, largely responsible for generating this controversy, may have a single explanation: a cascade effect resulting from inactivation of the zinc-binding abilities of insulin. After excluding six genes possibly affected by insulin inactivation, analyses of all available sequence data (7,117 nucleotide sites, 3,099 amino acid sites) resulted in strong support for rodent monophyly (94% BP for DNA sequences, 90% for protein sequences), which lends support to the insulin-cascade hypothesis.
Donor KIR haplotype B improves progression-free and overall survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma
Authors: N Kröger, T Zabelina, J Berger, H Duske, E Klyuchnikov, T Binder, T Stübig, Y Hilde-brandt, D Atanackovic, H Alchalby, F Ayuk, A R Zander, U Bacher, T Eiermann
Journal: Leukemia (2011)
Anaphylaxis treatment: current barriers to adrenaline auto-injector use
Authors: T. T. Song, M. Worm, P. Lieberman
Journal: Allergy (2014)

Anaphylaxis is a life-threatening condition that is increasing in prevalence in the developed world. There is universal expert agreement that rapid intramuscular injection of adrenaline is life-saving and constitutes the first-line treatment of anaphylaxis. The unpredictable nature of anaphylaxis and its rapid progression makes necessary the availability of a portable emergency treatment suitable for self-administration. Thus, anaphylaxis treatment guidelines recommend that at-risk patients are provided with adrenaline auto-injectors (AAIs). Despite these clear recommendations, current emergency treatment of anaphylaxis continues to be inadequate in many cases. The aim of this review is to highlight the barriers that exist to the use and availability of AAIs and that prevent proper management of anaphylaxis. In addition, we review the characteristics of all AAIs that are presently available in Europe and the USA and discuss the need for regulatory requirements to establish the performance characteristics of these devices.
Immunopathogenesis of the Acquired Immunodeficiency Syndrome
Authors: D. L. BOWEN
Journal: Annals of Internal Medicine (1985)

Many abnormalities of humoral and cellular immunity associated with the acquired immunodeficiency syndrome can be explained by the preferential infection of the T4 lymphocyte subset with the etiologic retrovirus. Severe alterations in specific T4 functions, such as inadequate immune responsiveness to specific antigen, result in devastating morbidity and mortality. On the basis of accumulated scientific knowledge, we outline the immunopathogenesis of this syndrome.Many abnormalities of humoral and cellular immunity associated with the acquired immunodeficiency syndrome (AIDS) can be explained by the preferential infection of the T4 lymphocyte subset with the etiologic retrovirus. Qualitative T-cell defects noted in AIDS patients include decreased blast transformation to mitogens and antigens, decreased lymphokine production, decreased alloreactivity, diminished cytotoxic cell response, and depressed helper function for B-cell immunoglobulin production. B lymphocytes are polyclonally activated in these patients. Theoretically, human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) infection may infect some subsets of immune cells, leading to a predominant cytopathic effect. In this situation, suppressed immune function may be due to a quantitative deficiency of the cell responsible for the function in question. Other cells may be infected by the virus in the absence of a resultant cytopathic effect, in which case suppressed immune function may be due to a quantitative effect in cells related directly or indirectly to genomic alterations. Recent data suggest that the T4 receptor may partially represent the membrane acceptor for infection by the etiologic virus. Further studies showed that preincubation of lymphocytes with monoclonal antibodies to distinct epitopes of the T4 glycoprotein blocked susceptible cell infection by LAV. The entire array of immunologic abnormalities may be explained by altered functions of the T4 inducer/helper lymphocyte subset. Such data lead to a hypothetic scheme for selective HTLV-III/LAV infection of the T4 helper/inducer lymphocyte and the resultant devastating effect this has on immune function in AIDS. Because of its central role in the induction and evolution of normal immune function by other effector cells, it is easy to see how a selective depletion or disruption of function of the T4 lymphocyte by HTLV-III results in severely altered, life-threatening immunity.
Membrane microviscosity is increased in the erythrocytes of patients with adrenoleukodystrophy and adrenomyeloneuropathy.
Authors: R A Knazek, W B Rizzo, J D Schulman, J R Dave
Journal: Journal of Clinical Investigation (1983)

Adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) are related X-linked disorders characterized by adrenal, gonadal, and nervous system dysfunction. While the pathologic finding common to these tissues appears to be the accumulation of excessive amounts of very long chain fatty acids, the mechanism leading to functional impairment in these tissues is unclear. Measurements of fluorescence polarization (P), using the lipid probe diphenylhexatriene, demonstrate a highly significant increase in the microviscosity of erythrocyte membranes in affected patients (P = 0.286 +/- 0.012) vs. normals (P = 0.239 +/- 0.020). Analyses of these membranes by gas-liquid chromatography revealed 1.9-, 1.6-, and 1.3-fold increases above normal values in the C25:0, C26:0, and C27:0 fatty acids, respectively. These observations are compatible with previously obtained data in animals that correlate membrane microviscosity with the number of hormone receptors in target tissues. The present data support the thesis that a decrease in responsiveness to trophic hormones in ALD and AMN is secondary to changes in the membrane microviscosity of the target tissues and suggest a mechanism by which adrenal and gonadal failure occur in such patients.
The outcome of IgD myeloma after autologous hematopoietic stem cell transplantation is similar to other Ig subtypes
Authors: Manish Sharma, Sofia R. Qureshi, Richard E. Champlin, Uday Popat, Sergio Giralt, Muzaffar H. Qazilbash
Journal: American Journal of Hematology (2010)

IgD myeloma is a rare subtype of myeloma that is associated with an aggressive course, resistance to chemotherapy, and a poor outcome. We identified 17 patients with IgD myeloma, who received a hematopoietic stem cell transplantation (HCT) at our institution between August 1988 and June 2008. Fifteen of these 17 patients underwent an autologous (auto) HCT. Complete responses (CRs) were seen in 6 of 15 (40%) patients; three converted from partial response to CR, two from minimal response to CR, and one from very good partial response to CR. The overall response rate after auto HCT was 86% (13 of 15). Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median PFS and OS were 18 and 45 months, respectively. These results were comparable with patients receiving autologous HCT for other Ig subtypes of myeloma.
Secretory Phospholipase A<sub>2</sub>Elicits Proinflammatory Changes and Upregulates the Surface Expression of Fas Ligand in Monocytic Cells
Authors: Marita Hernández, Lucía Fuentes, Francisco Javier Fernández Avilés, Mariano Sánchez Crespo, María Luisa Nieto
Journal: Circulation Research (2002)

Type IIA secretory phospholipase A 2 (sPLA 2 ) is an acute-phase reactant that plays a role in atherogenesis and is expressed in atherosclerotic arterial walls displaying inflammatory features. This generates a relevant question addressing the biological effects of this enzyme on monocytic cells, in view of the role of these cells in the inflammatory process associated with atherosclerosis. sPLA 2 produced a mild activation of the p42 mitogen-activated protein module of the mitogen-activated protein kinase (MAPK) cascade and a prominent activation of c-Jun N-terminal kinase in THP-1 monocytes. This activation showed both an early and a late peak, different from that elicited by tumor necrosis factor-α (TNF-α), which only showed the first peak. This was accompanied by activation of arachidonate metabolism, as judged from both the activation of the cytosolic phospholipase A 2 (cPLA 2 ) and the induction of cyclooxygenase-2 (COX-2) expression. sPLA 2 also elicited the production of monocyte chemoattractant protein-1 (MCP-1) and showed a synergistic effect with TNF-α on both COX-2 induction and MCP-1 production. sPLA 2 upregulated the expression of Fas ligand at the cell surface, but it did not influence Fas expression nor cell survival of monocytes. In summary, these data indicate that some of the atherogenic effects of sPLA 2 can be exerted by engagement of an sPLA 2 -binding structure on monocytic cells, most probably the M-type receptor for sPLA 2 , which produces the activation of the MAPK cascade, induces a proinflammatory phenotype, and upregulates the cell surface expression of Fas ligand.
HATH1 Expression in Mucinous Cancers of the Colorectum and Related Lesions
Authors: Eun Taek Park, Hee Kyung Oh, James R. Gum, Suzanne C. Crawley, Sanjay Kakar, Juan Engel, Ching Ching Leow, Wei-Qiang Gao, Young S. Kim
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Mucinous cancers and signet ring carcinomas are distinct classes of colon cancers characterized by their production of copious quantities of intestinal goblet cell mucin, MUC2. Deletion of transcription factor HATH1 ablates the biogenesis of goblet cells in developing mouse intestine, and forced expression of HATH1 results in elevated expression of MUC2 in colon cancer cells. The aim of this study was to assess the possible role of HATH1 in the development of mucinous cancers and signet ring carcinomas. Experimental Design: Immunohistochemistry and confocal microscopy was used to examine HATH1 expression and subcellular distribution in normal colon and small intestine, mucinous cancers, signet ring carcinomas, and nonmucinous cancers and in precursor lesions, including hyperplastic polyps, serrated adenomas, tubular adenomas, and villous adenomas. We also analyzed the transactivation of MUC2 promoter/reporter constructs by a HATH1 expression vector. Results: HATH1 expression transactivated MUC2 promoter/reporter constructs, an activity that was significantly inhibited by mutation of putative HATH1-binding sites. HATH1 was expressed in the nuclei of goblet cells and in the cytoplasm and nuclei of enteroendocrine cells of the colon. In the small intestine, only cytoplasmic expression of HATH1 in enteroendocrine cells was detected. HATH1 was found to be strongly expressed in the nuclei of hyperplastic polyps, serrated adenomas, villous adenomas, mucinous cancers, and signet ring carcinomas but repressed in nonmucinous cancers and tubular adenomas. Conclusions: This study confirms the importance of HATH1 for the development of intestinal secretory cells. The results further suggest that HATH1 is an important factor in the up-regulation of MUC2 expression that occurs in mucinous cancers and signet ring carcinomas. In addition, the expression of HATH1 in hyperplastic polyps, serrated adenomas, and villous adenomas lends support to the hypothesis that these neoplasms are frequent precursors in mucinous cancer and signet ring carcinoma development.
STUDIES OF A MYXOVIRUS RECOVERED FROM PATIENTS WITH INFECTIOUS HEPATITIS
Authors: Philip H. Prose, Samuel D. Balk, Harvey Liebhaber, Saul Krugman
Journal: The Journal of Experimental Medicine (1965)

WB virus has been shown to have a fine structure which is characteristic of members of the mumps-NDV-parainfluenza group of viruses. Viral internal component has been demonstrated within the cytoplasm of infected cells. The incorporation of internal component into virus filaments at the cell surface has also been demonstrated. The evidence presented suggests that virus filament formation occurs by a process of invagination of the cell membrane about the coiled strands of internal component lying beneath the membrane.