tbuckley/cabot-search huggingface dataset:
Chronic amiodarone-induced inhibition of the Na+–K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone
Authors: Andrew D Pitt, Clyne Fernandes, Nerida L Bewick, Paul D Hemsworth, Kerrie A Buhagiar, Peter S Hansen, Helge H Rasmussen, Leigh Delbridge, David W Whalley
Journal: Cardiovascular Research (2002)

To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status.New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+) pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks.Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current.The inhibitory effect of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the effects on heart rate and QT(c) are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na(+)-K(+) pump.
Diagnosis of Pneumocystis carinii pneumonia in HIV antibody positive patients by simple outpatient assessments.
Authors: D E Smith, A Forbes, S Davies, S E Barton, B G Gazzard
Journal: Thorax (1992)

As increasing numbers of patients with immunosuppression induced by the human immunodeficiency virus (HIV) present with respiratory symptoms it is important to differentiate Pneumocystis carinii pneumonia from other chest diseases rapidly and start treatment early. The management of pneumocystis pneumonia could be improved if clinicians could diagnose this condition confidently on the basis of simple clinical assessments.Three hundred and eighteen patients with evidence of immunosuppression due to HIV infection and suspected pneumocystis pneumonia were investigated. A clinical history was taken and arterial blood gas analysis, chest radiography, oximetry during exercise, and sputum induction or bronchoscopy (or both) were performed.Pneumocystis pneumonia was confirmed microscopically from induced sputum or bronchoalveolar lavage fluid in 154 patients; 118 had other chest disease. The remaining 46 patients had no definitive diagnosis. The best single independent predictors of a diagnosis of pneumocystis pneumonia were exercise induced oxygen desaturation and obvious interstitial infiltrates on the chest radiograph (odds ratios of 4.88 and 5.44 respectively). The symptom triad of exertional dyspnoea, cough, and fevers; the absence of pneumocystis pneumonia prophylaxis; and resting arterial hypoxaemia were less predictive (odds ratio 2.07, 3.72, and 0.69). An algorithm was developed that gave a positive predictive value for confirmed pneumocystis pneumonia of 95% and also identified those patients with a very small chance of having pneumocystis pneumonia (negative predictive value 85%).The diagnosis of an initial episode of pneumocystis pneumonia can be confidently made in a large proportion of immunosuppressed patients with respiratory symptoms on the basis of clinical symptoms, the absence of prophylaxis, chest radiographic appearances, and oxygen desaturation during exercise as shown by oximetry. Using these simple features clinicians can rapidly assign patients to the appropriate type of management at presentation.
Tracking the Molecular Evolution of Calcium Permeability in a Nicotinic Acetylcholine Receptor
Authors: Marcela Lipovsek, Angélica Fierro, Edwin G. Pérez, Juan C. Boffi, Neil S. Millar, Paul A. Fuchs, Eleonora Katz, Ana Belén Elgoyhen
Journal: Molecular Biology and Evolution (2014)

Nicotinic acetylcholine receptors are a family of ligand-gated nonselective cationic channels that participate in fundamental physiological processes at both the central and the peripheral nervous system. The extent of calcium entry through ligand-gated ion channels defines their distinct functions. The α9α10 nicotinic cholinergic receptor, expressed in cochlear hair cells, is a peculiar member of the family as it shows differences in the extent of calcium permeability across species. In particular, mammalian α9α10 receptors are among the ligand-gated ion channels which exhibit the highest calcium selectivity. This acquired differential property provides the unique opportunity of studying how protein function was shaped along evolutionary history, by tracking its evolutionary record and experimentally defining the amino acid changes involved. We have applied a molecular evolution approach of ancestral sequence reconstruction, together with molecular dynamics simulations and an evolutionary-based mutagenesis strategy, in order to trace the molecular events that yielded a high calcium permeable nicotinic α9α10 mammalian receptor. Only three specific amino acid substitutions in the α9 subunit were directly involved. These are located at the extracellular vestibule and at the exit of the channel pore and not at the transmembrane region 2 of the protein as previously thought. Moreover, we show that these three critical substitutions only increase calcium permeability in the context of the mammalian but not the avian receptor, stressing the relevance of overall protein structure on defining functional properties. These results highlight the importance of tracking evolutionarily acquired changes in protein sequence underlying fundamental functional properties of ligand-gated ion channels.
Critical considerations on the utility of FDG‐PET/CT for posttreatment restaging of the bone marrow in diffuse large B‐cell lymphoma
Authors: Amie E. Jackson, Thomas E. Witzig
Journal: American Journal of Hematology (2014)

We thank Adams and Kwee for their inquiry and constructive comments. We agree with the authors, and have stated such, that our study is limited by the small number of total patients and especially those with a positive bone marrow biopsy (BMB) at restaging after frontline therapy. As mentioned in our discussion, a larger retrospective cohort study would be difficult to perform, as less than 10% of patients have BM involvement by diffuse large B cell lymphoma (DLBCL) at diagnosis. Substantially, fewer would be expected to have a persistent positive BMB following therapy. We also agree with the authors that the utility of positron emission tomography (PET) for the initial staging of the BM in DLBCL patients is limited by variable sensitivity and inconsistent results regarding the prognostic implications of a PET-positive BM. However, our data suggests that the absence of 18F-fluorodeoxyglucose (FDG) uptake on a restaging PET-CT is highly correlated with a negative BMB. In this scenario, repeating the BMB is unlikely to provide significant information beyond that obtained by the PET-CT. It is to be remembered that a BMB, even if done bilaterally, samples only several cubic millimeters of bone marrow space as opposed to a PET-CT that images the entire marrow space. Therefore, PET-CT alone may be sufficient to confirm CR in routine clinical practice. In addition, if the PET-CT does show evidence of bone marrow uptake outside the posterior iliac crest, that FDG-avid area could be biopsied with an image-guided technique rather than simply a traditional BMB on the posterior iliac crest. As acknowledged in our conclusions, these findings are being prospectively evaluated in the ongoing ECOG1412 trial of rituximab, cyclophosphamide, adriamycin, vincristine, prednisone (R-CHOP) versus lenalidomide plus RCHOP in untreated DLBCL. This trial is performing BMB and PET-CT on all patients pretreatment and on those with a positive BMB posttreatment. ECOG1412 and other large DLBCL trials that now specifically integrate PET-CT into the response criteria will provide more definitive answers to this clinical practice issue. Amie E. Jackson AND Thomas E. Witzig Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
Tumor Cell Adhesion to Endothelial Cells: Endothelial Leukocyte Adhesion Molecule-1 as an Inducible Adhesive Receptor Specific for Colon Carcinoma Cells
Authors: D. Lauri, L. Needham, I. Martin-Padura, E. Dejana
Journal: JNCI Journal of the National Cancer Institute (1991)

Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms. [J Natl Cancer Inst 83: 1321–1324, 1991]
EFFECT OF HYPERTENSION AND DIABETES ON HIGH SYNTAX SCORE IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Young Jin Youn, Ji Hyun Lee, Jun&ndash;Won Lee, Min&ndash;Soo Ahn, Sung&ndash;Gyun Ahn, Jang&ndash;Young Kim, ByungSu Yoo, Seung Hwan Lee, Junghan Yoon, Kyung Hoon Choe
Journal: Journal of the American College of Cardiology (2012)
Role of Parathyroid Hormone–Related Protein in the Regulation of Stretch-Induced Renal Vascular Smooth Muscle Cell Proliferation
Authors: Eric Schordan, Sandra Welsch, Sylvie Rothhut, Alain Lambert, Mariette Barthelmebs, Jean-Jacques Helwig, Thierry Massfelder
Journal: Journal of the American Society of Nephrology (2004)

<i>In vivo</i>, vascular smooth muscle cells (VSMC) are continuously exposed to mechanical cyclic stretch as a result of the pulsatile blood flow from the cardiac contractile cycle. Stretch is altered in pathologic conditions and contributes to vascular remodeling by modulating VSMC proliferation and death. Parathyroid hormone–related protein (PTHrP) is a locally produced poly-protein that regulates cell growth. It was shown previously that PTHrP inhibits VSMC proliferation through the auto/paracrine pathway by interacting with its receptor, the PTH1R, but stimulates VSMC proliferation through the intracrine pathway by translocating into the nucleus. In the current study, VSMC that were isolated from both resistance and compliance vessels were used to study the role of PTHrP in VSMC proliferation under experimental stretch. It is shown that PTHrP gene expression is upregulated by stretch and that PTHrP opposes the inhibitory effect induced by stretch on VSMC proliferation through the intracrine pathway. In addition, it is demonstrated that PTHrP expression is controlled at the post-transcriptional level by stretch. Taken together, these results strongly suggest that PTHrP plays a critical role in the modulation of VSMC proliferation in response to stretch. Thus, in conditions in which stretch is increased, such as in hypertension or in restenosis after angioplasty, PTHrP may contribute to vessel hyperplasia.
HTLV-I-SPECIFIC ANTIBODY IN AIDS PATIENTS AND OTHERS AT RISK
Authors: Marjorie Robert-Guroff, Bijan Safai, EdwardP. Gelmann, PeterW.A. Mansell, JeromeE. Groopman, GurdipS. Sidhu, AlvinE. Friedman-Kien, AnneC. Bayley, DouglasW. Blayney, Michael Lange, JordanW. Gutterman, JamesL. Goedert, NealH. Steigbigel, JoyceM. Johnson, Robert Downing, RobertC. Gallo
Journal: The Lancet (1984)
STUDIES ON GONOCOCCUS INFECTION
Authors: Thomas M. Buchanan, Emil C. Gotschlich
Journal: The Journal of Experimental Medicine (1973)

Comparable numbers of types 1, 2, 3, and 4 gonococci were placed on the intact chorioallantoic membrane of 236, 10-day old chick embryos. Types 1 and 2 organisms produced infection and could be cultured from chorioallantoic fluid 2 days later significantly more often (69%) than types 3 and 4 organisms (12%, P < 0.001). This confirms in an animal model the same correlation between colony types and infectivity observed in human volunteers and suggests that types 1 and 2 gonococci possess a fundamental virulence characteristic which is absent from types 3 and 4 organisms. Gonococcal infection of the chick embryo chorioallantoic cavity remains a useful model somewhat analogous to localized gonococcal infection in man.
Prognosis and prognostic factors in adult patients with atopic dermatitis: a long-term follow-up questionnaire study
Authors: M.H. Sandstrom, J. Faergemann
Journal: British Journal of Dermatology (2004)

Background Atopic dermatitis (AD) is a chronic relapsing skin disease. Several investigations concerning the long-term prognosis of AD among children and teenagers have been performed but there are only few data among adults. Objectives To investigate the prognosis and prognostic factors in adult patients with AD by a long-term follow-up (25–38 years). The prognostic factors were defined as those factors of importance for the persistence of AD. Patients and methods A follow-up questionnaire was sent in November/December 1998 to 922 AD patients examined in our outpatient clinic between 1960 and 1973 among 1366 registered patients with AD. The patients were aged 20 years or older when they visited the clinic and 45 years or older when they answered the follow-up questionnaire. Results The response rate was 90·4%. The age range at the time of follow-up was 45–86 years (mean 55 years). Of the 833 patients who responded, 59% reported AD at some time during the last 12 months, which we defined as persistent AD. The mean value of clearance rate per person-years was 18%. One of the most important factors associated with persistence of AD was a head and neck dermatitis with or without other AD locations at the time of examination according to the old patient records. Conclusions This study showed that the majority of adults with AD still had AD when they became older. This applies particularly if negative prognostic factors existed.
Birth Outcome in Women with Previously Treated Breast Cancer—A Population-Based Cohort Study from Sweden
Authors: Kristina Dalberg, Johan Eriksson, Lars Holmberg
Journal: PLoS Medicine (2006)

Background Data on birth outcome and offspring health after the appearance of breast cancer are limited. The aim of this study was to assess the risk of adverse birth outcomes in women previously treated for invasive breast cancer compared with the general population of mothers. Methods and Findings Of all 2,870,932 singleton births registered in the Swedish Medical Birth Registry during 1973–2002, 331 first births following breast cancer surgery—with a mean time to pregnancy of 37 mo (range 7–163)—were identified using linkage with the Swedish Cancer Registry. Logistic regression analysis was used. The estimates were adjusted for maternal age, parity, and year of delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate infant health and mortality, delivery complications, the risk of preterm birth, and the rates of instrumental delivery and cesarean section. The large majority of births from women previously treated for breast cancer had no adverse events. However, births by women exposed to breast cancer were associated with an increased risk of delivery complications (OR 1.5, 95% CI 1.2–1.9), cesarean section (OR 1.3, 95% CI 1.0–1.7), very preterm birth (<32 wk) (OR 3.2, 95% CI 1.7–6.0), and low birth weight (<1500 g) (OR 2.9, 95% CI 1.4–5.8). A tendency towards an increased risk of malformations among the infants was seen especially in the later time period (1988–2002) (OR 2.1, 95% CI 1.2–3.7). Conclusions It is reassuring that births overall were without adverse events, but our findings indicate that pregnancies in previously treated breast cancer patients should possibly be regarded as higher risk pregnancies, with consequences for their surveillance and management.
Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci
Authors: John D Reveille, Anne-Marie Sims, Patrick Danoy, David M Evans, Paul Leo, Jennifer J Pointon, Rui Jin, Xiaodong Zhou, Linda A Bradbury, Louise H Appleton, John C Davis, Laura Diekman, Tracey Doan, Alison Dowling, Ran Duan, Emma L Duncan, Claire Farrar, Johanna Hadler, David Harvey, Tugce Karaderi, Rebecca Mogg, Emma Pomeroy, Karena Pryce, Jacqueline Taylor, Laurie Savage, Panos Deloukas, Vasudev Kumanduri, Leena Peltonen, Sue M Ring, Pamela Whittaker, Evgeny Glazov, Gethin P Thomas, Walter P Maksymowych, Robert D Inman, Michael M Ward, Millicent A Stone, Michael H Weisman, B Paul Wordsworth, Matthew A Brown
Journal: Nature Genetics (2010)
Effect of furosemide on the response of laryngeal receptors to low-chloride solutions
Authors: F B Sant'Ambrogio, G Sant'Ambrogio, J W Anderson
Journal: European Respiratory Journal (1993)

Laryngeal irritant receptors are stimulated by water and solutions lacking chloride ions, such as isotonic dextrose. It has been reported that furosemide (frusemide) reduces cough evoked by inhalation of low-chloride solutions. We studied the effect of furosemide on the response of laryngeal receptors to isotonic dextrose. Experiments were performed on nine dogs anaesthetized, spontaneously breathing through a tracheostomy, and with the upper airway functionally isolated. We recorded the activity of 13 laryngeal irritant receptors. Isotonic dextrose (4 ml) was instilled into the laryngeal lumen, before and after administration of a furosemide solution (3.75 mg.ml-1) into the upper airway. Before furosemide, dextrose increased the activity of the 13 receptors from 1.0 +/- 0.5 to 25.0 +/- 3.5 impulses (imp).s-1 (average discharge in the first 10 s of activation) and, 1-2 min after furosemide, from 0.3 +/- 0.2 to 13.4 +/- 3.2 imp.s-1; the difference between the stimulation by dextrose before and after furosemide was statistically significant. In contrast, the response to distilled water of four respiratory-modulated mechano-receptors (known to be activated by low-osmolality solutions) was not modified by furosemide. These results suggest that the furosemide-mediated inhibition of cough induced by inhalation of low-chloride solutions is, at least in part, due to the inhibitory effect of this substance on irritant receptor stimulation.
Isolation and Metastatic Properties of Detachment Variants of 816 Melanoma Cells 2
Authors: Eve Barak Briles, Stuart Kornfeld
Journal: JNCI Journal of the National Cancer Institute (1978)

Variant clones of B16 melanoma cells have been isolated that detached from plastic tissue culture dishes either more or less readily than the parent line upon treatment with EDTA or ethyleneglycol-bis(b-amino ethyl ether)N,N′-tetraacetic acid. Cells that detached more readily were spindlier in culture than parent cells, covered less surface area per cell, and formed fewer pulmonary tumors when injected iv into C57BL/6J mice. Cells that detached less readily were flatter in culture and formed more pulmonary tumors when injected iv than the parent cells. After detachment with EDTA, the cells reattached to culture dishes at the same rate.
What is the contribution of occupational environmental factors to the occurrence of scleroderma in men?
Authors: A.J Silman, S Jones
Journal: Annals of the Rheumatic Diseases (1992)

An occupational analysis of 56 men with scleroderma in the United Kingdom showed no evidence that silica exposure was implicated in the onset of the disease, in contrast with older published reports suggesting that such exposure explained an important proportion of the occurrence of the disease in men. Of the major occupational exposures suggested from case reports, only organic solvents were reported to any extent in this series. No significant increase in exposure to organic solvents was noted, however, in a case control analysis.
The Use of Lithium in Affective Disorders, III: A Double-Blind Study of Prophylaxis in Bipolar Illness
Authors: FRANK STALLONE, EDWARD SHELLEY, JULIEN MENDLEWICZ, RONALD R. FIEVE
Journal: American Journal of Psychiatry (1973)

The authors studied 52 manic-depressive patients who were assigned to either lithium or placebo during their normal interval phases for periods up to 28 months. Patients receiving lithium had fewer manic and depressive episodes per patient-year than placebo patients. However, this difference may have been due to a sample bias produced by a large dropout rate among patients who had manic episodes. The findings also suggest a relationship between response to lithium and family history of bipolar illness.
Screening for Osteoporosis in Postmenopausal Women With Breast Cancer Receiving Aromatase Inhibitors: Less Is More?
Authors: Sukhbinder K. Dhesy-Thind
Journal: Journal of Clinical Oncology (2012)

Advancing age is associated with an increased risk of both breast cancer and osteoporosis. Aromatase inhibitors (AIs) are commonly used to reduce the risk of recurrence in postmenopausal women with early-stage, hormone receptor–positive breast cancer. Estrogen has favorable effects on bone, including stimulation of new bone formation, whereas it inhibits bone resorption through cytokine-mediated osteoclastogenesis. 1 AIs, by inducing an estrogen-depleted state, have been shown to have adverse effects on bone mineral density (BMD) and are associated with fracture rates that vary from 1% to 4%. 2-6 This is seen with both nonsteroidal (letrozole or anastrazole) and steroidal (exemestane) AIs. The use of tamoxifen in the comparator group complicates these studies, given that it functions as an estrogen agonist in bone tissue, thereby preserving bone density and increasing the difference in observed BMD compared with AIs. 7 After completion of treatment, fracture rates return to normal. 8 Markers of bone turnover are also significantly increased with AI treatment. 2-6 The recently reported bone mineral density substudy of the NCIC Clinical Trials Group, MAP.3, a trial of prophylactic exemestane in postmenopausal women at increased risk for breast cancer, provides clarification of the effects of AIs on BMD in the absence of a tamoxifen comparison group. 9 An absolute difference of 1.34% in