tbuckley/cabot-search huggingface dataset:
STUDIES ON THE TRANSPLANTED HEART
Authors: C. Chiba, P. L. Wolf, S. Gudbjarnason, A. Chrysohou, H. Ramos, B. Pearson, R. J. Bing
Journal: The Journal of Experimental Medicine (1962)

The metabolic changes in the homografted canine heart were studied in order to define the biochemical alterations accompanying homograft rejection. In several experiments, homograft rejection was accelerated by prior sensitization of the host animal. The homografted heart released pyruvate and lactate as well as malic dehydrogenase and aldolase. Extraction of glucose by the graft usually remained positive. During the accelerated rejection, the release of pyruvate and lactate was more pronounced, and even glucose appeared in increased concentrations in coronary vein blood. In many experiments the respiratory quotient of the transplanted heart as well as its glucose-oxygen extraction ratio were elevated. It seemed likely that the elevated respiratory quotients were the result of conversion of carbohydrates to fat, since the injection of thiamine hydrochloride resulted in further elevation of the respiratory quotient and in an increased myocardial pyruvate extraction. Apparently, thiamine corrected a metabolic block at the level of the cocarboxylase. The metabolic block or blocks present in the transplanted heart are likely to be the result of diminution in intracellular enzymes and coenzymes resulting from increased cellular permeability. The redox potential across the transplanted heart was positive, indicating the absence of anoxia. The results illustrate that glycolysis proceeds in the transplanted heart in the presence of oxygen. Histopathologic and histochemical studies show the earliest lesion to be an accumulation of lymphocytes around vessels at 3 hours. Swelling of vascular endothelium occurs. By 5 hours a polar perivascular cellular infiltrate of lymphocytes, plasma cells, macrophages, and histiocytes exists. Changes following at 19 hours show the appearance of Aschoff- and Anitschkow-like cells. Granulomatous myocarditis which was first perivascular became interstitial with lymphocytic and histiocytic invasion of the myocardium. After 8 days acceleration of swelling of vascular endothelium and granulomatous lesions were observed and necrosis of the myocardium was prominent. Endothelial hyperplasia occurred at 14 days. In the accelerated reaction these changes were intensified and necrosis began as early as 4 hours after grafting. Histochemical changes of DPNH diaphorase, lactic, malic, and succinic dehydrogenase showed only significant diminution of malic dehydrogenase in the cardiac muscle which was concurrent with the increase of this enzyme in the serum.
Evolution of the mitochondrial rps3 intron in perennial and annual angiosperms and homology to nad5 intron 1
Authors: J. Laroche, J. Bousquet
Journal: Molecular Biology and Evolution (1999)

The plant mitochondrial rps3 intron was analyzed for substitution and indel rate variation among 15 monocot and dicot angiosperms from 10 genera, including perennial and annual taxa. Overall, the intron sequence was very conserved among angiosperms. Based on length polymorphism, 10 different alleles were identified among the 10 genera. These allelic differences were mainly attributable to large indels. An insertion of 133 nucleotides, observed in the Alnus intron was partially or completely absent in the other lineages of the family Betulaceae. This insertion was located within domain IV of the secondary-structure model of this group IIA intron. A mobile element of 47 nucleotides that showed homology to sequences located in rice rps3 intron and in intergenic plant mitochondrial genomes was found within this insertion. Both substitution and indel rates were low among the Betulaceae sequences, but substitution rates were increasingly larger than indel rates in comparisons involving more distantly related taxa. From a secondary-structure model, regions involved in helical structures were shown to be well preserved from indels as compared to substitutions, but compensatory changes were not observed among the angiosperm sequences analyzed. Using approximate divergence times based on the fossil record, substitution and indel rate heterogeneity was observed between different pairs of annual and perennial taxa. In particular, the annual petunia and primrose evolved more than 15 and 10 times faster, for substitution and indel rates respectively, than the perennial birch and alder. This is the first demonstration of an evolutionary rate difference between perennial and annual forms in noncoding DNA, lending support to neutral causes such as the generation time, population size, and speciation rate effects to explain such rate heterogeneity. Surprisingly, the sequence from the rps3 intron had a high identity with the sequence of intron 1 from the angiosperm mitochondrial nad5 gene, suggesting a common origin of these two group IIA introns.
Reviews and Notes: Emergency Medicine: Observation Medicine; and Presenting Signs and Symptoms in the Emergency Department: Evaluation and Treatment
Authors: Frederic W. Platt
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 April 1994Reviews and Notes: Emergency Medicine: Observation Medicine; and Presenting Signs and Symptoms in the Emergency Department: Evaluation and TreatmentFrederic W. PlattFrederic W. PlattSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-7-199404010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Observation MedicineLouis G. Graff; ed. 440 pages. Stoneham, Massachusetts: Andover Medical Publishers; 1993. $55.00.Presenting Signs and Symptoms in the Emergency Department: Evaluation and TreatmentGlenn C. Hamilton; ed. 815 pages. Baltimore: Williams & Wilkins; 1993. $95.00.Remember when emergency medicine was a new specialty? When its practitioners were renaming hospital emergency rooms as emergency departments? Now Graff and coauthors have defined a new field of medical practice: “Observation Medicine”At least 30% of U.S. hospitals have observation units, and, in many that lack around-the-clock physician staffing, the care of such patients falls to the emergency department staff. In ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1994Volume 120, Issue 7Page: 624KeywordsEmergency departmentEmergency medicineFallsHospital medicineLibrariesMedicareOutpatientsPatientsResidencySigns and symptoms ePublished: 15 August 2000 Issue Published: 1 April 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A New Quantitative Basis for Electrocardiographic Theory: The Normal QRS Complex
Authors: ERNEST FRANK, CALVIN F. KAY, GEORGE E. SEIDEN, ROBERT A. KEISMAN
Journal: Circulation (1955)

A theory of electrocardiography based on a fixed-location, eccentric-dipole representation of ventricular depolarization and a homogeneous, resistive, linear medium in the shape of the human torso yields quantitative predictions of instantaneous amplitude and shape of QRS body surface potentials on one normal human subject to an accuracy of approximately ±15 per cent for electrodes dispersed over the entire torso.
Systemic vascular resistance: an unreliable index of left ventricular afterload.
Authors: R M Lang, K M Borow, A Neumann, D Janzen
Journal: Circulation (1986)

Systemic vascular resistance (SVR) is a frequently used clinical index of left ventricular afterload. However, SVR may not adequately assess left ventricular afterload (i.e., ventricular internal fiber load during systole) since it reflects only peripheral vasomotor tone. In contrast, left ventricular end-systolic wall stress (sigma es) reflects the combined effects of peripheral loading conditions and left ventricular chamber pressure, dimension, and wall thickness. To determine the relationship between SVR and sigma es, left ventricular afterload and contractility were pharmacologically altered in eight dogs instrumented with central aortic microtip and Swan-Ganz thermodilution catheters. Left ventricular wall thicknesses and dimensions were measured from two-dimensionally targeted M mode echocardiograms. Aortic, right atrial, and left ventricular end-systolic pressures as well as cardiac output were recorded. SVR and sigma es were determined under control conditions as well as during infusions of nitroprusside, methoxamine, dobutamine, and norepinephrine. Control data acquired before each drug infusion were similar. When compared with baseline values, SVR underestimated the magnitude of change in left ventricular sigma es by 22% when afterload alone was decreased (nitroprusside), 54% when afterload alone was increased (methoxamine), and 50% when afterload was decreased and contractility was augmented (dobutamine). Most importantly, when afterload was minimally decreased in association with augmented contractility (norepinephrine), SVR increased by 21% while sigma es fell by 9%. Thus, discordant changes in left ventricular afterload (i.e., sigma es) and SVR can occur during pharmacologic interventions. SVR is an unreliable index of left ventricular afterload, reflecting only peripheral arteriolar tone rather than left ventricular systolic wall force. This emphasizes the fact that a true measure of left ventricular afterload must consider the interaction of factors internal and external to the myocardium.
Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance
Authors: Thomas Meinert Larsen, Stine-Mathilde Dalskov, Marleen van Baak, Susan A. Jebb, Angeliki Papadaki, Andreas F.H. Pfeiffer, J. Alfredo Martinez, Teodora Handjieva-Darlenska, Marie Kunešová, Mats Pihlsgård, Steen Stender, Claus Holst, Wim H.M. Saris, Arne Astrup
Journal: New England Journal of Medicine (2010)

Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power.We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet.A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events.In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.).
Diagnosis of calcium pyrophosphate dihydrate crystal deposition disease: ultrasonographic criteria proposed
Authors: B Frediani
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To investigate by high frequency ultrasonography the appearance of calcium pyrophosphate dihydrate (CPPD) calcifications, in the most commonly affected sites in CPPD disease, and the relationship between ultrasonographic CPPD deposits and the presence of CPPD crystals in synovial fluid. <b>Methods:</b> Three ultrasonographic patterns of CPPD calcification were identified and 11 patients enrolled. A control group comprised 13 patients with no evidence of CPPD deposits. Synovial fluid was aspirated from all patients and controls and examined for identification of crystals. All patients underwent a standard radiography examination at the same sites investigated by ultrasound. <b>Results:</b> In all patients with ultrasonographically defined CPPD deposits, CPPD crystals were found in the synovial fluid. In two cases, standard radiographic examination did not show evidence of the calcific deposits that were identified by ultrasonography. CPPD crystals were not found in the synovial fluid of controls. In four control group patients, ultrasonography identified calcifications defined as deposits of another nature. <b>Conclusions:</b> The ultrasonographic pattern used in this study for the diagnosis of CPPD disease demonstrated a very high correlation with the presence of CPPD crystals in synovial fluid. Ultrasonography demonstrated a sensitivity and specificity at least equal to that of radiography in identifying CPPD crystal calcifications.
Nomogram for Overall Survival of Patients With Progressive Metastatic Prostate Cancer After Castration
Authors: Oren Smaletz, Howard I. Scher, Eric J. Small, David A. Verbel, Alex McMillan, Kevin Regan, W. Kevin Kelly, Michael W. Kattan
Journal: Journal of Clinical Oncology (2002)

To develop a pretreatment prognostic model for survival of patients with progressive metastatic prostate cancer after castration using parameters that are measured during routine clinical management.Pretreatment clinical and biochemical determinants from 409 patients enrolled onto 19 consecutive therapeutic protocols from June 1989 through January 2000 were evaluated. The factors selected were age, Karnofsky performance status (KPS), hemoglobin (HGB), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALK), and albumin. These factors were combined in an accelerated failure time regression model to produce a nomogram to predict median, 1-year, and 2-year survival. The nomogram was validated internally and externally using data from a multicenter randomized trial of suramin plus hydrocortisone versus hydrocortisone alone.The median survival of the entire group was 15.8 months (range, 0.9 to 77.8 months); 87% have died. In multivariable analysis, KPS, HGB, ALK, albumin, and LDH were significantly associated with survival (P <.05), whereas age and PSA were not. All seven factors were included in the nomogram. When applied to the external validation data set, the nomogram achieved a concordance index of 0.67. Calibration plots suggested that the nomogram was well calibrated for all predictions.A nomogram derived from pretreatment parameters that are measured on a routine basis was constructed. It can be used to predict the median, 1-year, and 2-year survival of patients with progressive castrate metastatic disease with reasonable accuracy. The information is useful to assess prognosis, guide treatment selection, and design clinical trials.
Michael David Arthur Heller
Authors: S. H. A. Heller
Journal: BMJ (2014)

<h3>Abstract</h3> Insertion of mobile DNA sequences typically has deleterious effects on host fitness, and thus diverse mechanisms have evolved to control mobile element proliferation across the tree of life. Mobility of the Ty1 retrotransposon in <i>Saccharomyces</i> yeasts is regulated by a novel form of copy number control (CNC) mediated by a self-encoded restriction factor derived from the Ty1 <i>gag</i> capsid gene that inhibits virus-like particle function. Here, we survey a panel of wild and human-associated strains of <i>S. cerevisiae</i> and <i>S. paradoxus</i> to investigate how genomic Ty1 content influences variation in Ty1 mobility. We observe high levels of mobility for a canonical Ty1 tester element in permissive strains that either lack full-length Ty1 elements or only contain full-length copies of the Ty1’ subfamily that have a divergent <i>gag</i> sequence. In contrast, low levels of canonical Ty1 mobility are observed in restrictive strains carrying full-length Ty1 elements containing canonical <i>gag</i>. Phylogenomic analysis of full-length Ty1 elements revealed that Ty1’ is the ancestral subfamily present in wild strains of <i>S. cerevisiae</i>, and that canonical Ty1 in <i>S. cerevisiae</i> is a derived subfamily that acquired <i>gag</i> from <i>S. paradoxus</i> by horizontal transfer and recombination. Our results provide evidence that variation in the ability of <i>S. cerevisiae</i> and <i>S. paradoxus</i> strains to repress canonical Ty1 transposition <i>via</i> CNC is encoded by the genomic content of different Ty1 subfamilies, and that self-encoded forms of transposon control can spread across species boundaries by horizontal transfer.
Association between Plasma CC16 Levels, the A38G Polymorphism, and Asthma
Authors: INGRID A. LAING, CEDRIC HERMANS, ALFRED BERNARD, PAUL R. BURTON, JACK GOLDBLATT, PETER N. LE SOUËF
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The effect of the A38G polymorphism on Clara cell secretory protein (CC16) gene expression and asthma was investigated by measuring plasma CC16 levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma CC16 levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma CC16 levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma CC16 levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for asthma diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma CC16 level, suggesting that the odds of asthma was largely mediated through altered plasma CC16 levels. The 38A sequence was associated with reduced plasma CC16 levels and individuals with lower plasma CC16 levels were more likely to have asthma. This provides further evidence for a significant role of the CC16 gene, 38A allele in the development of asthma.
The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration
Authors: Christoph W. Strey, Maciej Markiewski, Dimitrios Mastellos, Ruxandra Tudoran, Lynn A. Spruce, Linda E. Greenbaum, John D. Lambris
Journal: The Journal of Experimental Medicine (2003)

Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFα induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–κB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.
Resolved
Authors: Wayne D. Comper
Journal: Journal of the American Society of Nephrology (2008)

The glomerular filtration barrier has long been thought largely impermeable to albumin. Startling new data suggest it may not be especially important in this process. Much of the argument hinges on whether charge selectivity really exists, how feasible it is for enormous quantities of albumin to instead be reclaimed by the proximal tubule, and the technical merits of previous experiments. Three experts in the field debate the merits of this argument.
The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flow
Authors: Amnon Peled, Valentin Grabovsky, Liliana Habler, Judith Sandbank, Frenando Arenzana-Seisdedos, Isabelle Petit, Herzl Ben-Hur, Tsvee Lapidot, Ronen Alon
Journal: Journal of Clinical Investigation (1999)

The chemokine SDF-1 plays a central role in the repopulation of the bone marrow (BM) by circulating CD34+ progenitors, but the mechanisms of its action remain obscure. To extravasate to target tissue, a blood-borne cell must arrest firmly on vascular endothelium. Murine hematopoietic progenitors were recently shown in vivo to roll along BM microvessels that display selectins and integrins. We now show that SDF-1 is constitutively expressed by human BM endothelium. In vitro, human CD34+ cells establish efficient rolling on P-selectin, E-selectin, and the CD44 ligand hyaluronic acid under physiological shear flow. ICAM-1 alone did not tether CD34+ cells under flow, but, in the presence of surface-bound SDF-1, CD34+ progenitors rolling on endothelial selectin rapidly developed firm adhesion to the endothelial surface, mediated by an interaction between ICAM-1 and its integrin ligand, which coimmobilized with SDF-1. Human CD34+ cells accumulated efficiently on TNF-activated human umbilical cord endothelial cells in the absence of SDF-1, but they required immobilized SDF-1 to develop firm integrin-mediated adhesion and spreading. In the absence of selectins, SDF-1 also promoted VLA-4–mediated, Gi protein–dependent tethering and firm adhesion to VCAM-1 under shear flow. To our knowledge, this is the first demonstration that SDF-1 expressed on vascular endothelium is crucial for translating rolling adhesion of CD34+ progenitors into firm adhesion by increasing the adhesiveness of the integrins VLA-4 and LFA-1 to their respective endothelial ligands, VCAM-1 and ICAM-1.