tbuckley/cabot-search huggingface dataset:
Histopathology of α1–Antitrypsin Liver Disease in A Transgenic Mouse Model
Authors: Stephen A. Geller, Stephen W. Nichols, Mark J. Dycaico, Katherine A. Felts, Joseph A. Sorge
Journal: Hepatology (1990)

Transgenic mice were constructed using human alpha 1-antitrypsin M and Z genomic clones. Livers of the M lineage mice showed slight cellular pleomorphism and immunohistochemically demonstrable finely granular alpha 1-antitrypsin material in hepatocytes. Z lineage mice with five gene copies per haploid mouse genome (Z#1) demonstrated fine granular alpha 1-antitrypsin material and a few large globules. In contrast, Z lineage mice with 12 gene copies per haploid mouse genome (Z#2) demonstrated hepatocytes filled with homogeneous, eosinophilic globules that were strongly reactive with diastase and periodic acid-Schiff and antibody to alpha 1-antitrypsin. Scattered microscopic polymorphonuclear leukocyte accumulations were seen that contained extracellular alpha 1-antitrypsin material, but there was neither histological nor serological evidence of mouse infectious hepatitis. In young animals, small clusters of hepatocytes lacking alpha 1-antitrypsin material were seen. These cells were the dominant population in older animals and formed nodular arrangements. Fibrosis was not demonstrable in neonatal and young animals or in any of the controls, but perisinusoidal fibrosis was seen in older Z#2 mice. Groups of hepatocytes without alpha 1-antitrypsin material showed dysplastic changes. We conclude that the transgenic mouse is a reliable and useful model in which to study the effects of alpha 1-antitrypsin in the liver because it demonstrates changes similar to those in the human disease.
New Technique for Determining Cardiac Output with Use of a Miniature Esophageal Scintillation Detector
Authors: ANTONIO HERNANDEZ, DAVID GOLDRING, MICHEL TER-POGOSSIAN, JOHN EICHLING
Journal: Circulation (1967)

A miniature scintillation detector recently designed and constructed in this laboratory can be inserted into the esophagus and under fluoroscopic vision positioned so that radioactivity emitted from the blood in the descending aorta can be detected and a time-concentration curve recorded from which cardiac output can be determined. Twenty simultaneous determinations of cardiac output by the isotope-dilution method with the esophageal scintillation counter probe and the dye-dilution technique were done in 10 dogs. There was a good correlation between the two methods. Among the technical advantages of the isotope-dilution method over the dye-dilution method are avoidance of arterial puncture, only one sample of venous blood required, an easily performed procedure, and ability to permit repeated determinations of cardiac output with a minimum of manipulation and trauma.
Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis
Authors: D. Henry, L. L-Y Lim, L. A G. Rodriguez, S. P. Gutthann, J. L Carson, M. Griffin, R. Savage, R. Logan, Y. Moride, C. Hawkey, S. Hill, J. T Fries, J. T Fries
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. <b>Design</b>: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. <b>Setting</b>: Hospital and community based casecontrol and cohort studies. <b>Main outcome measures</b>: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. <b>Results</b>: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. <b>Conclusions</b>: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs. <h3>Key messages</h3> Because there are no important differences in efficacy, choice of first line treatment with these drugs should be based on their relative toxicity Meta-analysis of the available epidemiological studies shows wide differences between individual drugs in the risk of inducing gastrointestinal bleed- ing and ulcer perforation Of the drugs in common use, ibuprofen and diclofenac rank low in toxicity whereas azapropa- zone, ketoprofen, and piroxicam rank high Some of the differences between drugs may be explained by dose, and the advantage of "low risk" drugs may be lost once their dose is increased
Anencephalic Newborns as Organ Donors
Authors: Robert D. Gillette
Journal: JAMA (1988)

<h3>To the Editor.—</h3> A recent commentary inTHE Journal<sup>1</sup>uses sophisticated reasoning and a variety of ethical arguments to arrive at the conclusion that our society should not condone the use of anencephalic infants with intact cardiorespiratory function as organ donors. After reading and rereading the article I find myself asking if this is not one of those times when intellectual analysis leads one away from the truth, not toward it. It is of little use, for example, to speculate on whether an anencephalic infant would want to be an organ donor if able to make a choice. He or she clearly will never have that luxury. Neither does it help to create a dichotomy between "persons" and "nonpersons" and to try to fit anencephalics into one category or the other. Arguments of this type are inherently unprovable and can continue interminably. The article by Arras and Shinnar<sup>1</sup>contains
Vaccination with Glycerinated Calf Lymph
Authors: A. E. Cope
Journal: BMJ (1902)

43that small-pox selected the mobst insanitary districts for itB field of operation in Glasgow.-Hospital Statistics.Referring now to experience of small-pox and vaccination, in Belvidere Hospital, Dr. Chalmers's Table VI teaches the TABLE VI.-Glasgow.-Smallbpox, 1900-1.-Returnas to Facci- nation of All Ca8es Yreated in Belvidere ASmall-pox Hospztal from April 1st, 1900, to June 30th, 1901.Vacciated.
One-step Nucleic Acid Amplification for Intraoperative Detection of Lymph Node Metastasis in Breast Cancer Patients
Authors: Masahiko Tsujimoto, Kadzuki Nakabayashi, Katsuhide Yoshidome, Tomoyo Kaneko, Takuji Iwase, Futoshi Akiyama, Yo Kato, Hitoshi Tsuda, Shigeto Ueda, Kazuhiko Sato, Yasuhiro Tamaki, Shinzaburo Noguchi, Tatsuki R. Kataoka, Hiromu Nakajima, Yoshifumi Komoike, Hideo Inaji, Koichiro Tsugawa, Koyu Suzuki, Seigo Nakamura, Motonari Daitoh, Yasuhiro Otomo, Nariaki Matsuura
Journal: Clinical Cancer Research (2007)

Detection of sentinel lymph node (SLN) metastasis in breast cancer patients has conventionally been determined by intraoperative histopathologic examination of frozen sections followed by definitive postoperative examination of permanent sections. The purpose of this study is to develop a more efficient method for intraoperative detection of lymph node metastasis.Cutoff values to distinguish macrometastasis, micrometastasis, and nonmetastasis were determined by measuring cytokeratin 19 (CK19) mRNA in histopathologically positive and negative lymph nodes using one-step nucleic acid amplification (OSNA). In an intraoperative clinical study involving six facilities, 325 lymph nodes (101 patients), including 81 SLNs, were divided into four blocks. Alternate blocks were used for the OSNA assay with CK19 mRNA, and the remaining blocks were used for H&E and CK19 immunohistochemistry-based three-level histopathologic examination. The results from the two methods were then compared.We established CK19 mRNA cutoff values of 2.5 x 10(2) and 5 x 10(3) copies/muL. In the clinical study, an overall concordance rate between the OSNA assay and the three-level histopathology was 98.2%. Similar results were obtained with 81 SLNs. The OSNA assay discriminated macrometastasis from micrometastasis. No false positive was observed in the OSNA assay of 144 histopathologically negative lymph nodes from pN0 patients, indicating an extremely low false positive for the OSNA assay.The OSNA assay of half of a lymph node provided results similar to those of three-level histopathology. Clinical results indicate that the OSNA assay provides a useful intraoperative detection method of lymph node metastasis in breast cancer patients.
Induction of Plasminogen Activator Inhibitor Type 1 and Type 1 Collagen Expression in Rat Cardiac Microvascular Endothelial Cells by Interleukin-1 and Its Dependence on Oxygen-Centered Free Radicals
Authors: Hitoshi Okada, Janet Woodcock-Mitchell, John Mitchell, Tomohiro Sakamoto, Kousuke Marutsuka, Burton E. Sobel, Satoshi Fujii
Journal: Circulation (1998)

Background —Ischemia with or without reperfusion induces the release of diverse products from monocytes, including cytokines such as interleukin-1 (IL-1). To determine whether these phenomena modulate fibrinolysis and potentially exacerbate impairment of the macrocirculation, microcirculation, or both, we characterized the effects of IL-1 on the expression of fibrinolytic system and matrix proteins in rat cardiac microvascular endothelial cells (CMECs). Methods and Results —Confluent CMECs were exposed to IL-1 in serum-free medium for 24 hours, and cell-conditioned medium was assayed for plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of plasminogen activators, and for type 1 collagen with Western blotting. IL-1 (2 ng/mL) specifically increased the accumulation of PAI-1 (4.4±0.6-fold; mean±SD; n=9) without affecting tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) levels, which remained unchanged. IL-1 increased the accumulation of collagen in conditioned media by 3.5±0.7-fold (n=6). Conversely, the accumulation of both PAI-1 and collagen induced by IL-1 was inhibited with an IL-1 receptor antagonist (200 ng/mL; n=6) and with cycloheximide (10 μg/mL; n=6), implying that protein synthesis was a requirement for the effect. To determine whether the IL-1 effect was mediated by induction of oxygen-centered free radical production, known to be induced by IL-1, we exposed the cells to the hydroxyl radical scavenger tetramethylthiourea (10 mmol/L) and observed abolition of the IL-1–induced increase in the expression of PAI-1 and collagen (n=6). Conversely, superoxides (generated with 10 mU/mL xanthine oxidase plus 0.6 mmol/L hypoxanthine, and 100 μmol/L hydrogen peroxide) induced the accumulation of PAI-1 and collagen (n=6). IL-1 (1 μg/kg body wt) and lipopolysaccharide (50 μg/kg body wt) administered in vivo increased PAI-1 protein in rat hearts as detected with Western blotting and PAI-1 immunostaining of rat heart microvessels, indicating the effects delineated in vitro were paralleled by effects in vivo. Conclusions —These results indicate that IL-1–induced oxygen-centered free radicals stimulate elaboration of PAI-1 and collagen by CMECs. Accordingly, microvascularly mediated inhibition of fibrinolysis may predispose to the persistence of microvascular thrombi, thereby contributing to impaired microcirculatory function, the no-reflow phenomenon, and cardiac dysfunction after ischemia and reperfusion.
Metabolism of Steroid and Amino Acid Moieties of Conjugated Bile Acids in Man III. CHOLYLTAURINE (TAUROCHOLIC ACID)
Authors: Gershon W. Hepner, John A. Sturman, Alan F. Hofmann, Paul J. Thomas
Journal: Journal of Clinical Investigation (1973)

After oral administration of [2,4-(3)H]-cholyl[(35)S]taurine to eight healthy subjects with indwelling nasoduodenal tubes, the specific activity of the cholyl and taurine moieties and the distribution of radioactivity in biliary bile acid and urinary metabolites, as well as total urinary and fecal (35)S and (3)H, were measured at intervals for 4-8 days. Similar measurements were made after [(35)S]taurine was given orally or intravenously or instilled into the distal intestine. The daily fractional turnover rate of the taurine moiety of cholyltaurine was low and similar to that of the cholyl moiety, indicating that deconjugation occurring during enterohepatic cycling was less than half that previously observed for glycine-conjugated bile acids. Some of the cholyl moiety was absorbed but, since reconjugation occurred predominantly with glycine, little reincorporation into the cholyltaurine pool was observed. Some of the taurine moiety was also absorbed intact but entered large taurine pools, and little reincorporation into the cholyltaurine pool was seen. Oral administration of taurine expanded the cholyltaurine pool and induced a decrease in the fractional turnover rate of the cholyl moiety of cholyltaurine, interpreted to indicate a greater reincorporation of the cholyl moiety because of increased reconjugation with taurine. Taurine moiety not absorbed as taurine appeared to be absorbed largely as sulfate which, like taurine, entered large endogenous pools. Little fecal excretion of (35)S occurred. (35)S was excreted in urine as taurine and sulfate, and excretion in the first 24 h (as percentage of administered dose) correlated highly (r = 0.93) with the daily fractional turnover rate of the taurine moiety. When taurine was instilled into the distal intestine, it appeared as such in plasma, but the more distal the site of instillation, the greater the fraction of urinary (35)S present as sulfate. The [(35)S]sulfate appeared to have come from bacterial degradation of [(35)S]taurine because, when [(35)S]taurine was given intravenously, (35)S was excreted in urine chiefly as [(35)S]taurine with little SO(4)=(-)[(35)S] being present.
Prevention of Systemic Arterial Embolism in Chronic Rheumatic Heart Disease by Means of Protracted Anticoagulant Therapy
Authors: JOHN C. WOOD, HADLEY L. CONN
Journal: Circulation (1954)

Seven clinic outpatients with mitral stenosis and auricular fibrillation complicated by systemic embolism have been maintained on Dicumarol for periods of 20 to 48 months. None has had a recognized embolism while on therapy. Dicumarol administration has been interrupted in each case for periods of six days to four months. Three additional systemic embolic episodes in two individuals occurred during this interval. Hemorrhagic manifestations have occurred on three occasions. The study suggests that: (a) protracted Dicumarol therapy is an effective means of preventing recurrent embolism in individuals with chronic rheumatic heart disease; (b) it is applicable to the average clinic outpatient.
Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium.
Authors: R S Kieval, J F Spear, E N Moore
Journal: Circulation Research (1992)

Abnormalities of myocardial gap junction-mediated cell coupling have been implicated in cardiac arrhythmogenesis. The potential role of gap junctional dysfunction in the generation of reperfusion-induced arrhythmias is uncertain. The purpose of this study was to measure the effects of myocardial ischemia and reperfusion on gap junctional conductance (gj) between isolated ventricular myocytes. By using a new experimental model, myocyte pairs were isolated from Langendorff-perfused rabbit hearts 1) after 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion, 2) after 75 minutes of control perfusion, or 3) immediately after removal of the heart. Myocytes and myocyte pairs were studied using whole-cell recording techniques. Action potential characteristics of cells in all three groups were normal. Despite similar mean gj in all three groups (0.88 +/- 0.27, 1.15 +/- 0.18, and 1.24 +/- 0.25 microS, respectively; p greater than 0.05), the postischemic group was more widely distributed and had a significantly greater proportion of poorly communicating cell pairs than either control group (gj less than 25% of mean in eight of 15 myocyte pairs versus zero of 15 and one of 13, respectively; p less than 0.02). Thus, postischemic myocyte pairs represent a heterogeneous population of electrically coupled cells in which individual deficits in coupling are masked by a normal mean value. In the reperfused intact heart, local disturbances of cell coupling, similarly undetected by gross measures of conduction, could disrupt myocardial conduction and activation on a microscopic scale and thus enhance arrhythmogenicity.
Different hepatocytes express the cholesterol 7α-hydroxylase gene during its circadian modulationin vivo
Authors: Caryn M. Berkowitz, Cynthia S. Shen, Bahri M. Bilir, Edgardo Guibert, Jorge J. Gumucio
Journal: Hepatology (1995)

Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile salt synthesis from cholesterol is a P450 enzyme (CYP7A). Its expression and activity are regulated by bile salts, cholesterol, hormones and a circadian modulator. Here we define the hepatocytes contributing to the expression of the rat CYP7A gene during its in vivo circadian variation. The diurnal expression of the CYP7A messenger RNA (mRNA) was studied by in situ hybridization and correlated with the diurnal rate of CYP7A gene transcription and mRNA expression. At 10 AM, the time of lowest mRNA expression and gene transcription rate, only four to five hepatocytes, located close to the hepatic venules ("perivenular"), contained the CYP7A mRNA. At 10 PM, the time of highest mRNA expression and fastest in vitro transcription rate, approximately one half of the hepatocytes (still in a "perivenular" location) contained the cholesterol 7 alpha-hydroxylase mRNA. In addition, the measured half-life of the CYP7A mRNA was shorter at 10 AM than at 10 PM suggesting that posttranscriptional mechanisms also contributed to the observed circadian differences. Therefore, the basal transcription rate of the CYP7A gene is maintained by four to five "perivenular" hepatocytes. During the circadian variation, the rate of gene transcription increases in these "perivenular" hepatocytes, but in addition, there is recruitment of other more proximal hepatocytes to transcribe the gene. It is proposed here that the response of specific hepatocytes to the various modulators of CYP7A gene expression is dependent on the relative position of these hepatocytes within the liver cell plate.
Electrophysiological effects of alprenolol on depressed canine myocardium
Authors: PAUL A GUSE, MARION S GAIDE, ROBERT J MYERBURG, KRISTINA EPSTEIN, HENRY GELBAND, ARTHUR L BASSETT
Journal: Cardiovascular Research (1980)

The electrophysiological effects of the β-adrenergic antagonist, alprenolol, were compared in normal and depressed canine myocardium. Both (+) and (±)-alprenolol (5 × 10−6 and 10−5 mol·litre−1) decreased action potential amplitude and max in Purkinje fibres superfused with Tyrode's solution in tissue bath. These concentrations shortened action potential duration and effective refractory period of Purkinje fibres but prolonged those of ventricular muscle. Alprenolol more markedly decreased max and sometimes prevented action potential propagation in Purkinje fibres overlying infarcted regions. Similar depressant actions were noted in Purkinje fibres depolarised by exposure to 9 mmol·litre−1 K+. Depolarised and diseased myocardium is more sensitive to alprenolol and the drug's membrane depressant actions may be significant in terminating arrhythmias in such tissue.
Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells.
Authors: Z Etzion, T Tiffert, R M Bookchin, V L Lew
Journal: Journal of Clinical Investigation (1993)

Elevated [Ca2+]i in deoxygenated sickle cell anemia (SS) red cells (RBCs) could trigger a major dehydration pathway via the Ca(2+)-sensitive K+ channel. But apart from an increase in calcium permeability, the effects of deoxygenation on the Ca2+ metabolism of sickle cells have not been previously documented. With the application of 45Ca(2+)-tracer flux methods and the combined use of the ionophore A23187, Co2+ ions, and intracellular incorporation of the Ca2+ chelator benz-2, in density-fractionated SS RBCs, we show here for the first time that upon deoxygenation, the mean [Ca2+]i level of SS discocytes was significantly increased, two- to threefold, from a normal range of 9.4 to 11.4 nM in the oxygenated cells, to a range of 21.8 to 31.7 nM in the deoxygenated cells, closer to K+ channel activatory levels. Unlike normal RBCs, deoxygenated SS RBCs showed a two- to fourfold increase in pump-leak Ca2+ turnover. Deoxygenation of the SS RBCs reduced their Ca2+ pump Vmax, more so in reticulocyte- and discocyte-rich than in dense cell fractions, and decreased their cytoplasmic Ca2+ buffering. Analysis of these results suggests that both increased Ca2+ influx and reduced Ca2+ pump extrusion contribute to the [Ca2+]i elevation.
IMPACTS OF ATRIAL FIBRILLATION SURGERY AND ADVERSE ATRIAL REMODELING ON TISSUE DOPPLER INDICES OF ATRIAL MECHANICAL TRANSPORT
Authors: Hrvoje Gasparovic, Maja Cikes, Tomislav Kopjar, Vedran Velagic, Ljiljana Hlupic, Davor Milicic, Bojan Biocina
Journal: Journal of the American College of Cardiology (2012)
A common core dysfunction in attention-deficit/hyperactivity disorder: A scientific red herring?
Authors: Edmund J. S. Sonuga-Barke, F. X. Castellanos
Journal: Behavioral and Brain Sciences (2005)

the reinforcement/extinction disorder hypothesis (sagvolden et al.) is an important counterweight to the executive dysfunction model of attention-deficit/hyperactivity disorder (adhd). however, like that model, it conceptualises adhd as pathophysiologically homogeneous, resulting from a common core dysfunction. recent studies reporting neuropsychological heterogeneity suggest that this common core dysfunction may be the scientific equivalent of a red herring.
Caring in Crisis. An Oral History of Critical Care Nursing
Authors: S. Jordan
Journal: BMJ (1995)

Jacqueline Zalumas, University of Pennsylvania Press, pounds sterling13.95, pp 230 ISBN 0 8122 1510 9

On both sides of the Atlantic nursing is gaining power and status as it moves into areas that were recently the province of medicine. Whether this is due to changes in the economic climate, in the education of nurses, or in technology remains uncertain. In these two books a professional writer and a nurse academic present nurse's accounts of their profession's transition to greater autonomy, independence, and accountability.

Nurse's increasing demands for professional autonomy are related to their changing roles and education. When as many as 18 out of a sample of 25 nurses hold higher degrees, it is unlikely that nursing will continue in the …