tbuckley/cabot-search huggingface dataset:
Cyclic Adenosine Monophosphate Modulation of Slow Calcium Influx Channels in Guinea Pig Hearts
Authors: AUGUST M. WATANABE, HENRY R. BESCH
Journal: Circulation Research (1974)

The relationship between cellular levels of cyclic adenosine monophosphate (AMP) and slow inward calcium ion (Ca 2+ ) current was studied in isolated perfused guinea pig hearts in which fast sodium ion (Na + ) channels had been inactivated by depolarization with potassium ions (K + ) or blockade with tetrodotoxin. Perfusion with 22 mM K + depolarized cardiac tissue to approximately -40 mv and rendered hearts inexcitable. Tetrodotoxin (3 x 10 -5 M) blocked excitability without altering resting membrane potential. Excitability and contractions could be restored to these hearts with a variety of inotropic agents that also raised the measured tissue levels of cyclic AMP or with high concentrations of Ca 2+ . The magnitude of steady-state tension developed by restored hearts was directly related to the external Ca 2+ concentration as well as to the concentration of the restoring agent used. The tension of restored hearts was markedly reduced by Ca 2+ -channel antagonists. Elevation of cyclic AMP levels preceded restoration of excitability to inactivated hearts. A highly significant positive correlation was found between the magnitude of Ca 2+ -dependent tension developed by restored hearts and the level of cyclic AMP in those hearts. Glucagon and ouabain, inotropic drugs that do not elevate myocardial levels of cyclic AMP, failed to restore depolarized or tetrodotoxin-blocked hearts. Therefore, cyclic AMP appears to modulate slow Ca 2+ influx channels in myocardial cells.
Expression of paramyxovirus V proteins promotes replication and spread of hepatitis C virus in cultures of primary human fetal liver cells
Authors: Linda Andrus, Svetlana Marukian, Christopher T. Jones, Maria Teresa Catanese, Timothy P. Sheahan, John W. Schoggins, Walter T. Barry, Lynn B. Dustin, Kartik Trehan, Alexander Ploss, Sangeeta N. Bhatia, Charles M. Rice
Journal: Hepatology (2010)

Abstract Here we demonstrate that primary cultures of human fetal liver cells (HFLC) reliably support infection with laboratory strains of hepatitis C virus (HCV), although levels of virus replication vary significantly between different donor cell preparations and frequently decline in a manner suggestive of active viral clearance. To investigate possible contributions of the interferon (IFN) system to control HCV infection in HFLC, we exploited the well-characterized ability of paramyxovirus (PMV) V proteins to counteract both IFN induction and antiviral signaling. The V proteins of measles virus (MV) and parainfluenza virus 5 (PIV5) were introduced into HFLC using lentiviral vectors encoding a fluorescent reporter for visualization of HCV-infected cells. V protein-transduced HFLC supported enhanced (10 to 100-fold) levels of HCV infection relative to untransduced or control vector-transduced HFLC. Infection was assessed by measurement of virus-driven luciferase, by assays for infectious HCV and viral RNA, and by direct visualization of HCV-infected hepatocytes. Live cell imaging between 48 and 119 hours postinfection demonstrated little or no spread of infection in the absence of PMV V protein expression. In contrast, V protein-transduced HFLC showed numerous HCV infection events. V protein expression efficiently antagonized the HCV-inhibitory effects of added IFNs in HFLC. In addition, induction of the type III IFN, IL29, following acute HCV infection was inhibited in V protein-transduced cultures. Conclusion: These studies suggest that the cellular IFN response plays a significant role in limiting the spread of HCV infection in primary hepatocyte cultures. Strategies aimed at dampening this response may be key to further development of robust HCV culture systems, enabling studies of virus pathogenicity and the mechanisms by which HCV spreads in its natural host cell population. (Hepatology 2011;)
Induced Pluripotent Stem Cells for Regenerative Medicine
Authors: Karen K. Hirschi, Song Li, Krishnendu Roy
Journal: Annual Review of Biomedical Engineering (2014)

With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.
Homeometric Autoregulation in the Heart
Authors: S. J. SARNOFF, J. H. MITCHELL, J. P. GILMORE, J. P. REMENSNYDER
Journal: Circulation Research (1960)

The effect of increasing the activity of the ventricle on its contractility was investigated. Several beats after the ventricle increases the amount of tension it develops per unit of time, it exhibits an increased contractility as shown by the increase in work and the more rapid development of pressure from a given end-diastolic pressure or fiber length. This has been termed homeometric autoregulation in contradistinction to the Frank-Starling or heterometric type of autoregulation. It was found that changes in coronary flow are not essential to the exhibition of this phenomenon. Possible mechanisms and the physiologic significance of the findings are discussed.
Constrictive Pericarditis in the Modern Era
Authors: Lieng H. Ling, Jae K. Oh, Hartzell V. Schaff, Gordon K. Danielson, Douglas W. Mahoney, James B. Seward, A. Jamil Tajik
Journal: Circulation (1999)

Background —The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. Methods and Results —The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P =0.011), but late survival was inferior to that of an age- and sex-matched US population (57±8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6±0.7 at baseline versus 1.5±0.8 at latest follow-up [ P &lt;0.0001]), with 83% being free of clinical symptoms. Conclusions —The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.
Reduction of Iron Stores and Cardiovascular Outcomes in Patients With Peripheral Arterial Disease
Authors: Leo R. Zacharski, Bruce K. Chow, Paula S. Howes, Galina Shamayeva, John A. Baron, Ronald L. Dalman, David J. Malenka, C. Keith Ozaki, Philip W. Lavori
Journal: JAMA (2007)

Accumulation of iron in excess of physiologic requirements has been implicated in risk of cardiovascular disease because of increased iron-catalyzed free radical-mediated oxidative stress.To test the hypothesis that reducing body iron stores through phlebotomy will influence clinical outcomes in a cohort of patients with symptomatic peripheral arterial disease (PAD).Multicenter, randomized, controlled, single-blinded clinical trial based on the Iron (Fe) and Atherosclerosis Study (FeAST) (VA Cooperative Study #410) and conducted between May 1, 1999, and April 30, 2005, within the Department of Veterans Affairs Cooperative Studies Program and enrolling 1277 patients with symptomatic but stable PAD. Those with conditions likely to cause acute-phase increase of the ferritin level or with a diagnosis of visceral malignancy within the preceding 5 years were excluded. Analysis was by intent-to-treat.Patients were assigned to a control group (n = 641) or to a group undergoing reduction of iron stores by phlebotomy with removal of defined volumes of blood at 6-month intervals (avoiding iron deficiency) (n = 636), stratified by hospital, age, and baseline smoking status, diagnosis of diabetes mellitus, ratio of high-density to low-density lipoprotein cholesterol level, and ferritin level.The primary end point was all-cause mortality; the secondary end point was death plus nonfatal myocardial infarction and stroke.There were no significant differences between treatment groups for the primary or secondary study end points. All-cause deaths occurred in 148 patients (23%) in the control group and in 125 (20%) in the iron-reduction group (hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.67-1.08; P = .17). Death plus nonfatal myocardial infarction and stroke occurred in 205 patients (32%) in the control group and in 180 (28%) in the iron-reduction group (HR, 0.88; 95% CI, 0.72-1.07; P = .20).Reduction of body iron stores in patients with symptomatic PAD did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke.Clinicaltrials.gov Identifier: NCT00032357.
THE DIAGNOSIS AND TREATMENT OF CHRONIC GONORRHOEA AND ITS LOCAL COMPLICATIONS
Authors: H. W. Bayly
Journal: BMJ (1914)

LOCK HOSPITAS.-IThas, until recently, been the habit in this cotntry to look upon gonorrhoea as a trivial affection, and only within the last few years have the severe and dangerous sequelae of this condition been recognized.;Neisser, the discoverer of tlhe gonococcus, considers that gonorrlhoea is the most widespread of all the infectious (liseases, with the exception of measles, and that probably this-disease is one of the most common causes of sterility, and hiis observations appear to be confirmed by other observers.Luys states: ."There can be no question that uncured gonorrhoea is one of the most frequent causes of a declining birth-rates that it cripples an -endless number of men, and that it renders legions of women sterile."It appears to be highly probable that over 50 per cent. of tlle inflammatory pelvic troubles so ,often met with in young married women are due to gonococcal infection by the husband, who, to do-him justice, is usually quite ignorant that he was not completely cured before marriage.It is a matter of great regret-indeed I feel inclined to put the matter more strongly and to say that it is a shame to our profession.thatso many men are told that they are free fronm all infection, and -are given perilssion to marvy before any systemaStic, thorough, and scientific examination lhas been made on.whichsuch an opinion can be logically based.The average young man-is not a blackguard, and if he were told by his medical man that after an attack of gonorrlhoea he must not marry until repeated examiiation enables a clean bill of hlealth to be given, and that if lhe does marry before such per- nmission is received lhe will run a grave risk of infecting hiis bride, he will, in the great majority of cases, follow his doctor's advice..-I -consider, therefore, that the responsibility of the prevalence of inflammatory pelvic conditions in young married women is shared equally between.thedoctor and the husband-indeed, -in many eases the doctor is the more to blame.-It behoves us, therefore, to remember that if we do not constitute ourselves thechampions of the innocent wife and unborn children, we shall deserve to be considered their enemies.It is, however, only by a systematic and tlhorough.routine examination that entails time, trouble, and skill that we ar-e able to give an opinion that is of any real value, or to state with any assurance that cureJias been effected.Chrooicity, oi>-s4wcalled latency of gonorrloea, has a definite cause,.and this cause can always, be found if a systematic searclh is-made for it.Criminals who are
Repression, suppression, and oppression (in depression)
Authors: Golan Shahar
Journal: Behavioral and Brain Sciences (2006)

Erdelyi's two key tenets – that repression may be conscious (“suppression”) and that it is context-sensitive – resonate well with findings on unipolar depression. Drawing from this field, I argue that (1) “oppression,” namely, pressure from significant others to refrain from attending to certain mental contents, influences individuals' repression/suppression; and that, (2) individuals actively create the very contexts that facilitate their repression/suppression.
Does This Patient Have Influenza?
Authors: Stephanie A. Call
Journal: JAMA (2005)

ContextInfluenza vaccination lowers, but does not eliminate, the risk of influenza. Making a reliable, rapid clinical diagnosis is essential to appropriate patient management that may be especially important during shortages of antiviral agents caused by high demand.ObjectivesTo systematically review the precision and accuracy of symptoms and signs of influenza. A secondary objective was to review the operating characteristics of rapid diagnostic tests for influenza (results available in <30 min).Data SourcesStructured search strategy using MEDLINE (January 1966-September 2004) and subsequent searches of bibliographies of retrieved articles to identify articles describing primary studies dealing with the diagnosis of influenza based on clinical signs and symptoms. The MEDLINE search used the Medical Subject Headings EXP influenza or EXP influenza A virus or EXP influenza A virus human or EXP influenza B virus and the Medical Subject Headings or terms EXP sensitivity and specificity or EXP medical history taking or EXP physical examination or EXP reproducibility of results or EXP observer variation or symptoms.mp or clinical signs.mp or sensitivity.mp or specificity.mp.Study SelectionOf 915 identified articles on clinical assessment of influenza-related illness, 17 contained data on the operating characteristics of symptoms and signs using an independent criterion standard. Of these, 11 were eliminated based on 4 inclusion criteria and availability of nonduplicative primary data.Data ExtractionTwo authors independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of clinical diagnostic findings. Differences were resolved by discussion and consensus.Data SynthesisNo symptom or sign had a summary LR greater than 2 in studies that enrolled patients without regard to age. For decreasing the likelihood of influenza, the absence of fever (LR, 0.40; 95% confidence interval [CI], 0.25-0.66), cough (LR, 0.42; 95% CI, 0.31-0.57), or nasal congestion (LR, 0.49; 95% CI, 0.42-0.59) were the only findings that had summary LRs less than 0.5. In studies limited to patients aged 60 years or older, the combination of fever, cough, and acute onset (LR, 5.4; 95% CI, 3.8-7.7), fever and cough (LR, 5.0; 95% CI, 3.5-6.9), fever alone (LR, 3.8; 95% CI, 2.8-5.0), malaise (LR, 2.6; 95% CI, 2.2-3.1), and chills (LR, 2.6; 95% CI, 2.0-3.2) increased the likelihood of influenza to the greatest degree. The presence of sneezing among older patients made influenza less likely (LR, 0.47; 95% CI, 0.24-0.92).ConclusionsClinical findings identify patients with influenza-like illness but are not particularly useful for confirming or excluding the diagnosis of influenza. Clinicians should use timely epidemiologic data to ascertain if influenza is circulating in their communities, then either treat patients with influenza-like illness empirically or obtain a rapid influenza test to assist with management decisions.
AUTOMOBILE ACCIDENTS, SUICIDE AND UNCONSCIOUS MOTIVATION
Authors: MELVIN L. SELZER, CHARLES E. PAYNE
Journal: American Journal of Psychiatry (1962)

Thirty alcoholic and 30 non-alcoholic Patients were evaluated to determine past serious suicidal preoccupation or previous suicidal attempts. These data were correlated with the total number of automobile accidents for which the patient was responsible. The 33 patients deemed to be suicidal averaged 2.70 accidents per patient whereas the 27 non-suicidal patients averaged 1.30 accidents. In the 30-patient alcoholic group, the 17 suicidal patients were responsible for 63 accidents, whereas the 13 non-suicidal patients were responsible for 24 accidents, yielding mean values of 3.70 and 1.77 accidents per person respectively. These differences were statistically significant. Due to the accepted and real hazards of driving, the automobile constitutes an ideal self-injurious or self-destructive instrument, particularly for persons intent upon camouflaging their suicidal motivation from others–and from themselves. With one exception, all patients believed their traffic accidents were fortuitous. Alcohol intoxication may be responsible for automobile accidents not only because of the resultant driving impairment, but also because of its potential for reducing the controlling and conforming function of the superego, thus releasing aggressive and self-destructive impulses which find expression in traffic "accidents." This investigation points toward the possibility that unconscious self-destructive impulses, sometimes abetted by alcohol intoxication, are a major although covert factor in the etiology of certain automobile accidents.
Premorbid IQ in Schizophrenia: A Meta-Analytic Review
Authors: Kristen A. Woodberry, Anthony J. Giuliano, Larry J. Seidman
Journal: American Journal of Psychiatry (2008)

Objective: Over the past three decades, there have been significant changes in the diagnostic criteria for schizophrenia as well as changes in measurement of IQ. The last quantitative review of the literature on premorbid IQ in schizophrenia was published more than two decades ago. Since that time, there have been many published studies of data sets pertaining to this issue. The purpose of the present review was to provide an updated meta-analysis of premorbid IQ in individuals who later develop schizophrenia. Method: The authors performed a systematic literature search, which yielded 18 studies that met criteria for the meta-analysis. Inclusion criteria were 1) premorbid psychometric measures of IQ in subjects who were later diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder, 2) similar comparison data, and 3) sufficient data for calculation of an effect size. The analogue to the analysis of variance method was used to model between-study variance due to key study-design features. Results: Overall, schizophrenia samples demonstrated a reliable, medium-sized impairment in premorbid IQ. The heterogeneity of effect sizes was minimal and almost exclusively the result of one study. Methodological differences, such as diagnostic criteria, type of IQ measure, sample ascertainment, and age at premorbid testing, contributed minimally to the effect size variance. A cross-sectional analysis of all studies by age and a descriptive review of studies that used repeated measures of IQ in a single sample did not support the presence of a relative decline in IQ during the premorbid period in individuals with schizophrenia. However, all studies with pre- and post-onset testing within the same sample suggested that a significant decline in the IQ of individuals with schizophrenia, relative to comparison subjects, was associated with the onset of frank psychosis. Conclusions: Years before the onset of psychotic symptoms, individuals with schizophrenia, as a group, demonstrate mean IQ scores approximately one-half of a standard deviation below that of healthy comparison subjects.
JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?
Authors: J Verbeeck, G Van Assche, J Ryding, E Wollants, K Rans, S Vermeire, M R Pourkarim, M Noman, J Dillner, M Van Ranst, P Rutgeerts
Journal: Gut (2008)

<h3>Background and aims:</h3> Anti-α4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease and in multiple sclerosis, but carries an estimated 1/1000 risk of progressive multifocal leukoencephalopathy (PML) caused by reactivation of latent JC virus infection. Athough anti-α4 integrin therapies are likely to be introduced in the clinic, screening for the risk of PML has not been developed. <h3>Methods:</h3> We prospectively collected urine, serum, plasma and buffy coats from 125 patients with Crohn's disease, 100 control subjects with gastrointestinal (GI) disease, and 106 healthy volunteers. Four to eight weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat samples from the 125 patients with Crohn's disease, and a next set of samples was collected 12–16 weeks after the first collection. JC viral loads were determined with quantitative real-time polymerase chain reaction (PCR), and JC virus seroprevalence with a specific enzyme-linked immunosorbant assay (ELISA). <h3>Results:</h3> The overall JC virus seroprevalence was 65%. JC virus DNA copies were detected in the urine from 29–44% of subjects, both those with Crohn's disease and controls. Median viral loads were significantly higher in patients with Crohn's disease who were immunosuppressed (7.36×10<sup>6</sup> copies/ml) compared to healthy volunteers (2.77×10<sup>5</sup> copies/ml) and compared to GI controls (1.8×10<sup>6</sup> copies/ml). Clearance at any time point occurred in 4/107 (3.7%) subjects only. JC viraemia was found in two patients with Crohn's disease. <h3>Conclusions:</h3> The natural history of JC virus in patients with Crohn's disease is still unknown. Our study results show that JC virus latency and urine viral shedding is frequent in immunosuppressed patients with Crohn's disease. More prospective studies are needed in order to agree on possible recommendations concerning the exclusion of patients with JCV viraemia from anti-α4 integrin treatment.
Radiographic appearance of bronchial carcinoid
Authors: R. L. Altman, W. E. Miller, D. T. Carr, W. S. Payne, L. B. Woolner
Journal: Thorax (1973)

<b>Altman, R. L., Miller, W. E., Carr, D. T., Payne, W. S., and Woolner, L. B. (1973).</b><i>Thorax</i>, <b>28</b>, 433-434. <b>Radiographic appearance of bronchial carcinoid.</b> The chest radiographs of 67 patients with bronchial carcinoid were reviewed. Seven had negative radiographs. Fifty-five had single abnormalities, the common manifestations being collapse or pneumonitis (21 patients), a small peripheral mass (20 patients), and a hilar or perihilar mass (11 patients). Five patients had multiple abnormalities, the most common combination being a mass with evidence of bronchial obstruction such as collapse of the related segment or lobe. Comparison with other reports revealed a significant difference in the frequency of the various abnormalities, a difference probably due to chance variations in the locations and to the age of the tumours at the time of diagnosis.