tbuckley/cabot-search huggingface dataset:
ALCOHOLISM, MENTAL ILLNESS AND THE "DRUNK DRIVER"
Authors: MELVIN L. SELZER, CHARLES E. PAYNE, JEAN D. GIFFORD, WILLIAM L. KELLY
Journal: American Journal of Psychiatry (1963)

A series of 67 drivers arrested for driving in an intoxicated state were examined to determine the incidence of alcoholism and psychic illness: 38 (57%) drivers were alcoholic, 10 (15%) were classified as "probably alcoholic," 4 were pre-alcoholic and 15 were not alcoholic. If the alcoholics, probable alcoholics and pre-alcoholics are considered together, no less than 78% of the arrested drivers had pathological drinking problems. At least 45 drivers (67%) suffered from recognizable psychiatric illness exclusive of alcoholism. Of the 52 pathological drinkers, 40 had classifiable psychiatric illness in addition to their drinking problem; 33 were personality disorders (29 passive-aggressive personalities, 2 sociopaths, 1 unstable personality, 1 paranoid personality), 4 were depressed and 3 schizophrenic. Of the 15 non-alcoholic drivers, 5 had personality disorders; 4 passive-aggressive personalities, and 1 sociopath. The entire group was heavily weighted toward the bottom of the socio-economic scale with 80% in Hollingshead's classes IV and V. Snce it is often postulated that alcoholinvolved accidents can be reduced by educating party-givers to modify their driving guests intake, the drinking site was elicited. Twenty-seven drivers did their prior drinking in taverns, 8 in private clubs, 10 at house parties, 6 at the home of friends, 4 in their automobiles and only 8 in their own homes. Contrary to popular belief, most alcoholics avoid solitary drinking and will weave their intoxicated way long distances to enjoy drinking companionship. This study lends support to the concept that the larger body of drinking drivers is distinct from the so-called "drunk drivers" who are responsible for a substantial number of serious traffic accidents and violations. It appears that many alcohol-involved traffic mishaps and violations are incurred by alcoholic persons whose abnormality immunizes them against the usual educacational appeals and legal devices intended to curb intoxicated driving. Detection of the alcoholic driver's addiction followed by rehabilitative efforts will help protect the community from repeated exposure to automotive depredations at the hands of the same accident-susceptible individuals. Alcoholic drivers convicted of alcohol-caused traffic offenses should be required to undergo treatment prior to resuming driving.
Survivin Expression Predicts Poorer Prognosis in Anaplastic Large-Cell Lymphoma
Authors: Ellen J. Schlette, L. Jeffrey Medeiros, Andre Goy, Raymond Lai, George Z. Rassidakis
Journal: Journal of Clinical Oncology (2004)

Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown.We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation.Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P =.007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P =.009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P =.03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV.Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.
Posttraumatic Stress Symptoms and Salivary Cortisol Levels
Authors: Hymie Anisman, Jenna Griffiths, Kimberly Matheson, Arun V. Ravindran, Zul Merali
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study assessed the relationship between posttraumatic stress symptoms and salivary cortisol levels after a severe ice storm. METHOD: Posttraumatic stress symptoms (Impact of Event Scale scores) and salivary cortisol levels were determined in 115 victims of an ice storm and in 27 healthy comparison subjects 1 month and approximately 1 year after the ice storm. RESULTS: One month after the storm, Impact of Event Scale scores for the victims (mean=20.31, SD=15.23) exceeded those of the comparison subjects (mean=5.30, SD=9.78) but were reduced approximately 1 year later (mean=14.01, SD=13.68). A quadratic relation was found to exist between Impact of Event Scale scores and cortisol levels. CONCLUSIONS: One month after the storm, cortisol levels were found to be elevated among the victims but were diminished among those with the highest Impact of Event Scale scores. This relationship was found not to exist approximately 1 year later.
Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells
Authors: Ramesh C. Nayak, Lisa R. Trump, Bruce J. Aronow, Kasiani Myers, Parinda Mehta, Theodosia Kalfa, Ashley M. Wellendorf, C. Alexander Valencia, Patrick J. Paddison, Marshall S. Horwitz, H. Leighton Grimes, Carolyn Lutzko, Jose A. Cancelas
Journal: Journal of Clinical Investigation (2015)

Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient-derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient-derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization.
Validation of the systemic lupus erythematosus responder index for use in juvenile-onset systemic lupus erythematosus
Authors: Rina Mina, Marisa S Klein-Gitelman, Shannen Nelson, B Anne Eberhard, Gloria Higgins, Nora G Singer, Karen Onel, Lori Tucker, Kathleen M O'Neil, Marilynn Punaro, Deborah M Levy, Kathleen Haines, Alberto Martini, Nicolino Ruperto, Daniel Lovell, Hermine I Brunner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). <h3>Methods</h3> The SRI considers changes in the SELENA–SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA–SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. <h3>Results</h3> The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. <h3>Conclusions</h3> The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.
Thin Filament-Based Modulation of Contractile Performance in Human Heart Failure
Authors: Teruo Noguchi, Mark Hünlich, Phillip C. Camp, Kelly J. Begin, Mohamed El-Zaru, Richard Patten, Bruce J. Leavitt, Frank P. Ittleman, Norman R. Alpert, Martin M. LeWinter, Peter VanBuren
Journal: Circulation (2004)

Background— The contribution of the sarcomere’s thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. Methods and Results— We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms α, β 1 , and β 2 was increased in failing human myocardium and reduced after left ventricular assist device support. Conclusions— These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.
GALACTOSE RESIDUES IN CHRONIC INFLAMMATORY DISEASE
Authors: R. Madhok, H.A. Capell, J.S. Axford, F.C. Hay, L. Mackenzie, D.A. Isenberg, P.M. Lydyard, I.M. Roitt, G. Rook, T.W. Rademacher, R.B. Parekh, R.A. Dwek
Journal: The Lancet (1988)
Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness
Authors: R. H. Green, C. E. Brightling, S. McKenna, B. Hargadon, N. Neale, D. Parker, C. Ruse, I. P. Hall, I. D. Pavord
Journal: European Respiratory Journal (2006)

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.
Ventilatory failure after Pasteurella multocida pneumonia.
Authors: P M Calverley, N J Douglas, D R Buchanan, A M Wilson
Journal: Thorax (1981)

Casereport A 62-year-old womanwasadmitted asanemergency with a seven-day history ofcoughproductive ofpurulent sputum. Twenty-four hoursbefore admission shehad becomeincreasingly breathless andtwohoursbefore admission shebecamedrowsy andlost consciousness. Shehadneverpreviously beenahospital inpatient but hadbeenseeninachest clinic 10years before because of exertional breathlessness. Pulmonary function testing at thattimeshowedmoderately severe airways obstruction (FEV,/FVC 09/24litres, predicted FEV,24+ 0-4litres andFVC 3-5+ 04litres). Shewasa life-long nonsmoker taking noregular medication. Onadmission shewascomatose, centrally cyanosed, and unresponsive topainful stimuli. Shewasclinically shocked with verypoorperipheral perfusion andbarely palpable peripheral pulses. Herapexbeat wasirregular with arate of160/minute andBP 100/50. Therespiratory ratewas 40/minute andshewasnoted tohaveaslight kyphosis, milddigital clubbing andbilateral mid-zone coarse crackles. Admission ECG confirmed atrial fibrillation witha ventricular reponsevarying between 150and 190/ minute while theinitial chest radiograph showedpatchy shadowing inbothupperzoneswithageneral reduction inpulmonary vascular markings. Theresident physician madeaclinical diagnosis ofleft ventricular failure and arterial blood gases taken10minutes after starting high flowoxygen treatment (6litres/minute vianasal cannulae) revealed anarterial Po2of10-4kPa(78mmHg),Pco2 11-7kPa(88mmHg),andhydrogen ion81mmol/l (pH709);shewasimmediately changed tolowflow oxygentherapy andphysiotherapy wasstarted. This yielded nosputum butrigid bronchoscopy produced large quantities ofpurulent secretion andthepatient's consciousness improved toa level whereshecouldspeak rationally butonlysingle wordswerepossible because of hersevere breathlessness. Post-bronchoscopy bloodgas
A dot-immunobinding assay for antimitochondrial antibodies
Authors: Edward Penner, Hans Goldenberg, Siegfried Meryn, Julian Gordon
Journal: Hepatology (1986)

A dot-immunobinding assay was established for the detection of antimitochondrial antibodies. Nitrocellulose strips were coated with sonicated rat liver mitochondria and incubated in the presence of human sera. The resulting immune complexes were visualized with an enzyme-linked second antibody. Antimitochondrial antibodies were found in the sera of 96% of patients with primary biliary cirrhosis, 17% of patients with autoimmune hepatitis and 4% of patients with progressive systemic sclerosis. Sera of patients with other liver diseases or with systemic lupus erythematosus, specimens positive for M1 and M3 mitochondrial antibodies and samples from normal controls were all negative. Antinuclear and other cytoplasmic antibodies were not detected in this assay. The dot-immunobinding assay for antimitochondrial antibodies is rapid and sensitive, and obviates the need for expensive equipment.
Early and nonreversible decrease of CD161++/MAIT cells in HIV infection
Authors: Cormac Cosgrove, James E. Ussher, Andri Rauch, Kathleen Gärtner, Ayako Kurioka, Michael H. Hühn, Krista Adelmann, Yu-Hoi Kang, Joannah R. Fergusson, Peter Simmonds, Philip Goulder, Ted H. Hansen, Julie Fox, Huldrych F. Günthard, Nina Khanna, Fiona Powrie, Alan Steel, Brian Gazzard, Rodney E. Phillips, John Frater, Holm Uhlig, Paul Klenerman
Journal: Blood (2012)
Genome-Wide Disruption of Gene Expression in Allopolyploids but Not Hybrids of Rice Subspecies
Authors: Chunming Xu, Yan Bai, Xiuyun Lin, Na Zhao, Lanjuan Hu, Zhiyun Gong, Jonathan F. Wendel, Bao Liu
Journal: Molecular Biology and Evolution (2014)

Hybridization and polyploidization are prominent processes in plant evolution.Hybrids and allopolyploids typically exhibit radically altered gene expression patterns relative to their parents, a phenomenon termed "transcriptomic shock."To distinguish the effects of hybridization from polyploidization on coregulation of divergent alleles, we analyzed expression of parental copies (homoeologs) of 11,608 genes using RNA-seq-based transcriptome profiling in reciprocal hybrids and tetraploids constructed from subspecies japonica and indica of Asian rice (Oryza sativa L.).The diploid hybrids and their derived allopolyploids differ dramatically in morphology, despite having the same suite of genes and genic proportions.Allelic and homoeolog-specific transcripts were unequivocally diagnosed in the hybrids and tetraploids based on parent-specific SNPs.Compared with the in silico hybrid (parental mix), the range of progenitor expression divergence was significantly reduced in both reciprocally generated F1 hybrids, presumably due to the ameliorating effects of a common trans environment on divergent cis-factors.In contrast, parental expression differences were greatly elaborated at the polyploid level, which we propose is a consequence of stoichiometric disruptions associated with the numerous chromosomal packaging and volumetric changes accompanying nascent polyploidy.We speculate that the emergent property of "whole genome doubling" has repercussions that reverberate throughout the transcriptome and downstream, ultimately generating altered phenotypes.This perspective may yield insight into the nature of adaptation and the origin of evolutionary novelty accompanying polyploidy.
Heme oxygenase 1 attenuates the development of atopic dermatitis–like lesions in mice: Implications for human disease
Authors: Mio Kirino, Yohei Kirino, Mitsuhiro Takeno, Yoji Nagashima, Kazuo Takahashi, Masayoshi Kobayashi, Shuji Murakami, Tsutomu Hirasawa, Atsuhisa Ueda, Michiko Aihara, Zenro Ikezawa, Yoshiaki Ishigatsubo
Journal: Journal of Allergy and Clinical Immunology (2008)
Vascular reactivity to noradrenaline, potassium chloride, and angiotensin II in the rat perfused mesenteric vasculature preparation, during the development of renal hypertension
Authors: M. G. COLLIS, B. J. ALPS
Journal: Cardiovascular Research (1975)

The degree of reactivity to noradrenaline of the perfused mesenteric vasculature and the blood pressure of the renal hypertensive rat were correlated. Early (true) supersensitivity was demonstrated for noradrenaline and angiotensin but not for KCl. Later (apparent) hyperreactivity to all three substances was related to an elevated maximal response. The potentiating actions of endogenous angiotensin could cause the early (true) supersensitivity to noradrenaline.
Gradients in the Regional Rates of Myocardial Rubidium-86 Clearance in Tranquilized Dogs
Authors: WILLIAM J. GILLESPIE, WILLIAM D. LOVE
Journal: Circulation Research (1967)

In order to determine what gradients in local rates of myocardial blood flow are present in the resting hemodynamic state, the regional rates of myocardial clearance of 86 Rb were measured in dogs tranquilized with chlorpromazine. The clearance rate in the left ventricle corresponded to an average coronary flow of 11.7 ml/g per 10 min. Estimated right ventricular flow was 7.1 ml/g per 10 min and left atrial flow 7.9 ml/g per 10 min. High rates of 86 Rb uptake were noted in the atrial appendages and papillary muscles. Uptake in serially sectioned cores from both ventricles was consistently highest near the endocardial surface and decreased toward the epicardium. Selective injections of 86 Rb into the aorta or vena cava demonstrated that isotope penetrated the myocardium from the cavities of both ventricles. In the right ventricle, high subendocardial 86 Rb clearance was not found unless the isotope had been present within its cavity. In the left ventricle, in contrast, more 86 Rb was taken up by the subendocardial zones, even when all of the tracer was distributed by coronary arterial blood. The results support both diffusion of 86 Rb and perfusion of the myocardium by intracavitary blood as mechanisms responsible for the uptake of 86 Rb from the heart cavities.
An evidence map of psychosocial interventions for the earliest stages of bipolar disorder
Authors: Martine Vallarino, Chantal Henry, Bruno Etain, Lillian J Gehue, Craig Macneil, Elizabeth M Scott, Angelo Barbato, Philippe Conus, Stefanie A Hlastala, Mary Fristad, David J Miklowitz, Jan Scott
Journal: The Lancet Psychiatry (2015)