tbuckley/cabot-search huggingface dataset:
Cardiovascular Effects of Fluoxetine in Depressed Patients With Heart Disease
Authors: Steven P. Roose, Alexander H. Glassman, Evelyn Attia, Sally Woodring, Elsa-Grace V. Giardina, J. Thomas Bigger
Journal: American Journal of Psychiatry (1998)

The purpose of this study was to determine the cardiovascular effects of fluoxetine in depressed patients with cardiac disease.Twenty-seven depressed patients (26% of whom were female and whose average age was 73 years) who had congestive heart failure, conduction disease, and/or ventricular arrhythmia were studied in an open medication trial of fluoxetine, up to 60 mg/day, for 7 weeks. The main outcome measures were heart rate and rhythm measured by 24-hour ECG recordings, ejection fraction determined by radionuclide angiography, cardiac conduction intervals, and blood pressure. Baseline values were compared with those at weeks 2 and 7 of fluoxetine treatment. In 60 comparable patients, values of these same cardiovascular measures at baseline and after 3 weeks of treatment with a tricyclic antidepressant, nortriptyline, were also examined.Fluoxetine induced a statistically significant 6% decrease in heart rate, a 2% increase in supine systolic pressure, and a 7% increase in ejection fraction. There was no effect on cardiac conduction, ventricular arrhythmia, or orthostatic blood pressure. Overall, 4% of the fluoxetine patients had an adverse cardiovascular effect. In contrast, nortriptyline treatment caused a significant increase in heart rate and orthostatic hypotension, and 20% of the nortriptyline-treated patients had an adverse cardiovascular effect.In depressed patients with heart disease, fluoxetine treatment was not associated with the cardiovascular effects documented for the tricyclic antidepressants or with significant adverse cardiac events. However, limited conclusions about fluoxetine's cardiovascular effects and safety can be drawn from this study of only 27 patients monitored for 7 weeks.
Mechanism of chloride secretion induced by carbachol in a colonic epithelial cell line.
Authors: K Dharmsathaphorn, S J Pandol
Journal: Journal of Clinical Investigation (1986)

Serosal application of carbachol to T84 cell monolayers mounted in an Ussing chamber caused an immediate increase in short circuit current (Isc) that peaked within 5 min and declined rapidly thereafter, although a small increase in Isc persisted for approximately 30 min. The increase in Isc was detectable with 1 microM carbachol; half-maximal with 10 microM carbachol; and maximal with 100 microM carbachol. Unidirectional Na+ and Cl- flux measurements indicated that the increase in Isc was due to net Cl- secretion. Carbachol did not alter cellular cAMP, but caused a transient increase in free cytosolic Ca2+ ([Ca2+]i) from 117 +/- 7 nM to 160 +/- 15 nM. The carbachol-induced increase in Isc was potentiated by either prostaglandin E1 (PGE1) or vasoactive intestinal polypeptide (VIP), agents that act by increasing cAMP. Measurements of cAMP and [Ca2+]i indicated that the potentiated response was not due to changes in these second messengers. Studies of the effects of these agents on ion transport pathways indicated that carbachol, PGE1, or VIP each increased basolateral K+ efflux by activating two different K+ transport pathways on the basolateral membrane. The pathway activated by carbachol was not sensitive to barium, while that activated by PGE1 or VIP was; furthermore, their action on K+ efflux are additive. Our study indicates that carbachol causes Cl- secretion, and that this action may result from its ability to increase [Ca2+]i and basolateral K+ efflux. Carbachol's effect on Cl- secretion is greatly augmented in the presence of VIP or PGE1, which open a cAMP-sensitive Cl- channel on the apical membrane, accounting for a potentiated response.
Prevalence of Incompletely Penetrant Huntington's Disease Alleles Among Individuals With Major Depressive Disorder
Authors: Roy H. Perlis, Jordan W. Smoller, Jayalakshmi Mysore, Mei Sun, Tammy Gillis, Shaun Purcell, Marcella Rietschel, Markus M. Nöthen, Stephanie Witt, Wolfgang Maier, Dan V. Iosifescu, Patrick Sullivan, A. John Rush, Maurizio Fava, Hans Breiter, Marcy Macdonald, James Gusella
Journal: American Journal of Psychiatry (2010)

Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established.This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression.CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats.In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles.
Comparison of Accuracy Measures of Two Screening Tests for Gestational Diabetes Mellitus
Authors: Marsha van Leeuwen, Egbert J.K. Zweers, Brent C. Opmeer, Evert van Ballegooie, Henk G. ter Brugge, Harold W. de Valk, Ben W.J. Mol, Gerard H.A. Visser
Journal: Diabetes Care (2007)

To compare the accuracy measures of the random glucose test and the 50-g glucose challenge test as screening tests for gestational diabetes mellitus (GDM).In this prospective cohort study, pregnant women without preexisting diabetes in two perinatal centers in the Netherlands underwent a random glucose test and a 50-g glucose challenge test between 24 and 28 weeks of gestation. If one of the screening tests exceeded predefined threshold values, the 75-g oral glucose tolerance test (OGTT) was performed within 1 week. Furthermore, the OGTT was performed in a random sample of women in whom both screening tests were normal. GDM was considered present when the OGTT (reference test) exceeded predefined threshold values. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the two screening tests. The results were corrected for verification bias.We included 1,301 women. The OGTT was performed in 322 women. After correction for verification bias, the random glucose test showed an area under the ROC curve of 0.69 (95% CI 0.61-0.78), whereas the glucose challenge test had an area under the curve of 0.88 (0.83-0.93). There was a significant difference in area under the curve of the two tests of 0.19 (0.11-0.27) in favor of the 50-g glucose challenge test.In screening for GDM, the 50-g glucose challenge test is more useful than the random glucose test.
Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol
Authors: Ming Zhou, Yuhua Zhao, Yan Ding, Hao Liu, Zixing Liu, Oystein Fodstad, Adam I Riker, Sushama Kamarajugadda, Jianrong Lu, Laurie B Owen, Susan P Ledoux, Ming Tan
Journal: Molecular Cancer (2010)

Abstract Background Taxol is one of the most effective chemotherapeutic agents for the treatment of patients with breast cancer. Despite impressive clinical responses initially, the majority of patients eventually develop resistance to Taxol. Lactate dehydrogenase-A (LDH-A) is one of the predominant isoforms of LDH expressed in breast tissue, which controls the conversion of pyruvate to lactate and plays an important role in glucose metabolism. In this study we investigated the role of LDH-A in mediating Taxol resistance in human breast cancer cells. Results Taxol-resistant subclones, derived from the cancer cell line MDA-MB-435, sustained continuous growth in high concentrations of Taxol while the Taxol-sensitive cells could not. The increased expression and activity of LDH-A were detected in Taxol-resistant cells when compared with their parental cells. The downregulation of LDH-A by siRNA significantly increased the sensitivity of Taxol-resistant cells to Taxol. A higher sensitivity to the specific LDH inhibitor, oxamate, was found in the Taxol-resistant cells. Furthermore, treating cells with the combination of Taxol and oxamate showed a synergistical inhibitory effect on Taxol-resistant breast cancer cells by promoting apoptosis in these cells. Conclusion LDH-A plays an important role in Taxol resistance and inhibition of LDH-A re-sensitizes Taxol-resistant cells to Taxol. This supports that Warburg effect is a property of Taxol resistant cancer cells and may play an important role in the development of Taxol resistance. To our knowledge, this is the first report showing that the increased expression of LDH-A plays an important role in Taxol resistance of human breast cancer cells. This study provides valuable information for the future development and use of targeted therapies, such as oxamate, for the treatment of patients with Taxol-resistant breast cancer.
Stress failure plays a major role in the development of high-altitude pulmonary oedema in rats
Authors: C. Bai, J. She, A. Goolaerts, Y. Song, C. Shen, J. Shen, Q. Hong
Journal: European Respiratory Journal (2009)

Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague–Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise. An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15–20 min breaks every 4 h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wet-to-dry weight (W/D) ratio and histological measurements were conducted on each animal. In rats exercising in hypoxia, BAL protein and lung W/D ratio were significantly increased but no changes in BAL leukotriene B 4 and immunoglobulin M were observed. In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling/disruption. Our study established a direct link between histological and physiological evidence of HAPE-like symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPE-like symptoms in Sprague–Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.
The night Bernard Shaw taught us a lesson
Authors: Michael O'Donnell
Journal: BMJ (2006)

of suicide after bereavement and here, again, Shakespeare has something to contribute, in the reported fates of Lady Macbeth and Lady Constance (table 1).Shakespeare recorded fainting under strong emotion on 18 occasions.Nowadays called vasovagal syncope, this often causes myoclonic jerks, easily misdiagnosed as epilepsy. 16 Emotional fainting is quite common, and its mechanisms are familiar-vagal bradycardia and hypotension from peripheral vasodilatation.In Marston's Antonio's Revenge, the Duchess of Genoa swoons when she hears that, contrary to what she had just been told, her missing husband is dead (another case of contrary emotions in dangerously quick succession).In the same play, the heroine Mellida swoons at the (false) news of her beloved Antonio being drowned and fails to recover consciousness; this was the one actual death from emotion that I came across in the works by Shakespeare's contemporaries.Shakespeare had no hesitation in going for dramatic effect by adding a death, a fit, or a faint to a play when this was absent from his source material, even with overtly historical plays such as Julius Caesar and Antony and Cleopatra.He may even have been more prone to include such "flags of feeling" in his work than other writers of his day, but this survey can do no more than hint at this.Does Shakespeare, with his unique insights into the human condition, 17 have a message for today's doctors?I think he does: never underestimate the power of the emotions to disturb bodily functions.
Oral Iron Supplementation After Blood Donation
Authors: Joseph E. Kiss, Donald Brambilla, Simone A. Glynn, Alan E. Mast, Bryan R. Spencer, Mars Stone, Steven H. Kleinman, Ritchard G. Cable
Journal: JAMA (2015)

Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic.
LYMPHOCYTE PROLIFERATION IN VITRO INDUCED BY HAPTEN AUTOLOGOUS PROTEIN CONJUGATES
Authors: Bent Rubin, Hans Wigzell
Journal: The Journal of Experimental Medicine (1974)

Immune lymph node cells from guinea pigs respond to soluble antigen in vitro by an increase in DNA synthesis. Optimal conditions for this proliferative response were studied in the present article. Under such conditions, immune cells showed increasing responses with increasing antigen concentration in vitro, the threshold dose of activation frequently being as low as 0.02 µg per culture. In contrast, normal lymph node cells (from FCA-stimulated animals) did only respond to antigen at very high doses (20 mg/culture), and immune cell dilution studies could be performed in normal cells without changing the kinetics of the antigen specific response of immune cells. Fractionation on anti-Ig columns indicated that purified, immune T lymphocytes were quite capable of proliferating in vitro upon antigen stimulation. However, our attempts to adsorb the proliferating cells onto chemically defined immunoadsorbants failed despite the fact that immune B cells (as measured by the rosette assay) were retained almost completely by such a procedure. Purified, immune T lymphocytes from guinea pigs immunized with different antigen concentrations in vivo and/or obtained at different times after immunization were tested for a differential sensitivity toward antigen-induced DNA synthesis in vitro. However, we were not able to demonstrate any regular increase in sensitivity to antigen in vitro, and if found, it seemed to be more dependent upon the number of antigen reactive cells in the population studied rather than upon differences in the average avidity of the receptors on the cells proliferating in vitro. The results in the present article are discussed in relation to current knowledge and hypotheses on T-lymphocyte receptors.
Molecular Pathogenesis of Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Pedro Farinha, Randy D. Gascoyne
Journal: Journal of Clinical Oncology (2005)

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occur in a number of anatomic sites, but share overlapping morphologic and immunophenotypic features. Helicobacter pylori infection has been identified as an etiologic factor in gastric MALT lymphoma, and a growing list of other infectious organisms have recently been shown to be associated with MALT lymphomas at other anatomic sites. Although cause and effect has not been established for most of these infectious agents, our understanding of the biology has significantly improved, in part through the application of standard cytogenetic analyses. The common karyotypic alterations that characterize MALT lymphomas include the trisomies 3 and 18, the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(q27;q32), and the recently described t(3;14)(p14.1;q32). This apparent complexity of cytogenetic alterations that have now been implicated in the pathogenesis of extranodal MALT lymphoma serves as a paradigm for molecular cross talk in neoplastic disease. Recent data have shown that at least three of the disparate translocations affect a common signaling mechanism, and thus unify all three under a common pathogenesis, resulting in the constitutive activation of the nuclear factor kappa B (NF-kappaB) pathway. It may be that the new MALT-related translocation involving the FOXP1 gene and other as yet undiscovered translocations may all have in common increased NF-kappaB signaling.
Role of the venous system in baroreceptor-mediated reflexes in man
Authors: Stephen E. Epstein, G. David Beiser, Morris Stampfer, Eugene Braunwald
Journal: Journal of Clinical Investigation (1968)

Although baroreceptor stimulation produced by marked alterations in arterial pressure has been shown to produce reflex changes in venous tone in animals, the effects on venous tone in man of altering arterial pressure within the physiologic range have not been clear. In six subjects, venous tone did not change when mean arterial pressure was raised by 25-40 mm Hg, although heart rate fell reflexly by 40%. Venous tone remained constant in 10 subjects when arterial pressure was lowered. This contrasted to the sustained rise in forearm vascular resistance and the persistent tachycardia that occurred. However, 12 subjects continued to respond to these interventions by transient venoconstriction. To eliminate possible emotional influences on venous tone due to the experimental intervention, venous responses were studied before and during general anesthesia in five of these subjects. In contrast to the response before anesthesia, an equivalent fall in arterial pressure during anesthesia no longer evoked a venoconstrictor response. Venous reactivity and the baroreceptor reflex arc remained intact during anesthesia, since venous tone always rose after a deep inspiration, and tachycardia always accompanied the fall in arterial pressure. It is concluded that changes in arterial pressure in the physiologic range in man do not induce measurable reflex alterations in venous tone, and that the increases sometimes seen with decreases in arterial pressure appear to be due to extraneous psychic factors.
Identification of a Unique Glomerular Factor X Activator in Murine Lupus Nephritis
Authors: SUBODINI PERAMPALAM, LUOQUAN WANG, NANCY MYERS-MASON, JEN NEI YEOW, NIR STANIETSKY, JAMES PHILLIPS, JEFFREY I. WEITZ, CAMERON ACKERLEY, GARY A. LEVY, EDWARD H. COLE
Journal: Journal of the American Society of Nephrology (1999)

The role of glomerular procoagulant activity (PCA) was studied in mice (MRL/lpr, NZBxWF,, and BXSB) that are known to develop lupus nephritis. In young mice (6 to 8 wk) without renal disease, there was no increase in spontaneous glomerular PCA. In contrast, older (5 to 8 mo) autoimmune mice had significant augmentation in glomerular PCA, coinciding with the histologic appearance of severe glomerulonephritis and renal fibrin deposition. The PCA was characterized as a serine protease that directly activated factor X. This factor X activator is not tissue factor because (1) expression of PCA was not dependent on factor VII; (2) a monoclonal antibody against the factor X activator inhibited glomerular PCA, but not tissue factor; (3) the molecular weight (66 kD) of the activator was different from that of tissue factor; and (4) concanavalin A inhibited tissue factor but not glomerular PCA. Immunohistochemical studies localized the factor X activator to the glomerular mesangium and capillary wall of 4- to 6-mo-old diseased MRL/lpr mice. Immunogold-labeled antibody bound to the dense deposits, macrophages, and endothelial cells of diseased glomeruli. These studies define the role of a unique glomerular factor X activator in murine lupus nephritis.
The combination of single-dose montelukast and loratadine on exercise-induced bronchospasm in children
Authors: D.G. Peroni, G.L. Piacentini, A. Pietrobelli, A. Loiacono, W. De Gasperi, A. Sabbion, R. Micciolo, A.L. Boner
Journal: European Respiratory Journal (2002)

The aim of the study was to evaluate the protective effect of single-dose, combination treatment comprising montelukast (5 mg) and loratadine (10 mg), on exercise-induced bronchoconstriction in asthmatic children. The combination was compared to placebo, loratadine and montelukast alone. Nineteen children were enrolled in a double-blind randomised, single-dose, crossover study. For each treatment patients undertook two treadmill exercise tests, 2 and 12 h respectively after single-dose administration. No significant differences were seen in the maximum fall in forced expiratory volume in one second (FEV<sub>1</sub>) 2 h after treatment and placebo. Whereas significant differences in maximum fall in FEV<sub>1</sub> were observed between treatment groups 12 h after administration. Loratadine alone did not show any significant protection or any additional effect in comparison with montelukast alone. Single doses of montelukast and montelukast plus loratadine were significantly more effective than loratadine at 12 h. The present study, performed using single-dose treatments, demonstrated that maximal protective effect by montelukast was obtained 12 h after dosing and that montelukast plus loratadine did not result in significant additive bronchoprotective effects on exercise-induced bronchoconstriction.
Distinct receptor and regulatory properties of recombinant mouse complement receptor 1 (CR1) and Crry, the two genetic homologues of human CR1.
Authors: H Molina, W Wong, T Kinoshita, C Brenner, S Foley, V M Holers
Journal: The Journal of Experimental Medicine (1992)

The relationship between the characterized mouse regulators of complement activation (RCA) genes and the 190-kD mouse complement receptor 1 (MCR1), 155-kD mouse complement receptor 2 (MCR2), and mouse p65 is unclear. One mouse RCA gene, designated MCR2 (or Cr2), encodes alternatively spliced 21 and 15 short consensus repeat (SCR)-containing transcripts that crosshybridize with cDNAs of both human CR2 and CR1, or CR2 alone, respectively. A five SCR-containing transcript derived from a second unique gene, designated Crry, also crosshybridizes with human CR1. We have previously shown that the 155-kD MCR2 is encoded by the 15 SCR-containing transcript. To analyze the protein products of the other transcripts, which are considered the genetic homologues of human CR1, we have expressed the 21 and the 5 SCR-containing cDNAs in the human K562 erythroleukemia cell line. We demonstrate that cells expressing the 21 SCR transcript express the 190-kD MCR1 protein. These cells react with five unique rat anti-MCR1 monoclonal antibodies, including the 8C12 antibody considered to be monospecific for MCR1. In addition, these cells efficiently form rosettes with mouse C3b-bearing sheep erythrocytes. In contrast, cells expressing the five SCR-containing Crry transcript are strongly recognized by an anti-human CR1 antibody that also defines the mouse p65 protein. Using a functional assay that measures the surface deposition of C3 activated via the classical complement pathway, we show that Crry/p65-expressing cells have a markedly decreased amount of C3 deposited on them as compared with control cells expressing the antisense construct or cells expressing MCR1 or MCR2. This suggests that Crry has intrinsic complement regulatory activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Explicit ads seek to halt rise in sexual disease
Authors: Trevor Jackson
Journal: BMJ (2004)

![][1] 

One of the spoof Valentine's Day cards

A government sexual health advertising campaign has given a new meaning to the traditional romantic Valentine's Day's message. In place of slushy slogans describing the pain of Cupid's dart are explicit warnings about the agony of gonorrhoea and genital herpes.”I love you so much it hurts… when I pee,” reads the message on the front of a spoof Valentine's card warning of the risks of contracting chlamydia from having …

 [1]: /embed/graphic-1.gif