tbuckley/cabot-search huggingface dataset:
Metabolic Imaging With β-Methyl- <i>p</i> -[ <sup>123</sup> I]-Iodophenyl-Pentadecanoic Acid Identifies Ischemic Memory After Demand Ischemia
Authors: Vasken Dilsizian, Timothy M. Bateman, Steven R. Bergmann, Roger Des Prez, Martin Y. Magram, Anne E. Goodbody, John W. Babich, James E. Udelson
Journal: Circulation (2005)

Background— After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, β-methyl- p -[ 123 I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later. Methods and Results— In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2±1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9±2.6 hours after ischemia ( P =NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect ( r =0.6, P &lt;0.001 for early BMIPP; r =0.5, P =0.005 for delayed BMIPP). Conclusions— Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.
Unfounded worries about cancer in patients attending a routine otolaryngology clinic
Authors: S. Ali
Journal: Journal of the Royal Society of Medicine (2005)

To investigate a suspicion that many ear, nose and throat patients have unfounded concerns about cancer, we questioned 50 patients who had attended a routine clinic after screening-out of those with possibly cancer-related features. None of the 50 proved to have cancer. 15 (30%) had been worried about cancer and 7 of these were still worried despite the consultation. Unwarranted fears about cancer are best dealt with by the referring clinician, especially when the wait for an appointment will be long. Such fears also need to be recognized and addressed by the specialist.
Cardiac Myosin-Binding Protein C Is Required for Complete Relaxation in Intact Myocytes
Authors: Lutz Pohlmann, Irena Kröger, Nicolas Vignier, Saskia Schlossarek, Elisabeth Krämer, Catherine Coirault, Karim R. Sultan, Ali El-Armouche, Saul Winegrad, Thomas Eschenhagen, Lucie Carrier
Journal: Circulation Research (2007)

The role of cardiac myosin-binding protein C (cMyBP-C) in cardiac contraction is still not fully resolved. Experimental ablation of cMyBP-C by various means resulted in inconsistent changes in Ca2+ sensitivity and increased velocity of force of skinned preparations. To evaluate how these effects are integrated in an intact, living myocyte context, we investigated consequences of cMyBP-C ablation in ventricular myocytes and left atria from cMyBP-C knock-out (KO) mice compared with wild-type (WT). At 6 weeks, KO myocytes exhibited mild hypertrophy that became more pronounced by 30 weeks. Isolated cells from KO exhibited markedly lower diastolic sarcomere length (SL) without change in diastolic Ca2+. The lower SL in KO was partly abolished by the actin-myosin ATPase inhibitors 2,3-butanedione monoxime or blebbistatin, indicating residual actin-myosin interaction in diastole. The relationship between cytosolic Ca2+ and SL showed that KO cells started to contract at lower Ca2+ without reaching a higher maximum, yielding a smaller area of the phase-plane diagram. Both sarcomere shortening and Ca2+ transient were prolonged in KO. Isolated KO left atria exhibited a marked increase in sensitivity to external Ca2+ and, in contrast to WT, continued to develop twitch force at low micromolar Ca2+. Taken together, the main consequence of cMyBP-C ablation was a defect in diastolic relaxation and a smaller dynamic range of cell shortening, both of which likely result from the increased myofilament Ca2+ sensitivity. Our findings indicate that cMyBP-C functions as a restraint on myosin-actin interaction at low Ca2+ and short SL to allow complete relaxation during diastole.
Acute Polyarthritis Associated With Active Epstein-Barr Virus Infection
Authors: C. George Ray
Journal: JAMA (1982)

Nine patients with an initial onset of symptoms of acute arthritis within the preceding four weeks were enrolled in a prospective serological study with clinical follow-up for six months to two years. Four adults with chronic rheumatoid arthritis and ten healthy adults were similarly studied. Serial titers measured included antibodies to Epstein-Barr virus (EBV) antigens, group B coxsackieviruses, rubella virus, cytomegalovirus, and herpes simplex virus. Serological evidence of active EBV infection was found in four of the patients with acute arthritis, none of the patients with chronic arthritis, and one of the ten healthy adults. There was no similar correlation between acute disease and presence of antibodies to the other viruses tested. We suggest that EBV may cause acute rheumatic illnesses more commonly than is currently appreciated but is probably not involved in the etiology of typical chronic rheumatoid arthritis. (<i>JAMA</i>1982;248:2990-2993)
Effect of alpha-adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts.
Authors: L Talosi, E G Kranias
Journal: Circulation Research (1992)

The intracellular events and specifically the role of protein kinase C-mediated protein phosphorylation, after alpha-adrenergic receptor stimulation of the heart, are not well understood. We examined the phosphorylation of sarcolemmal, sarcoplasmic reticular, myofibrillar, and cytosolic proteins in perfused beating rabbit hearts on activation of protein kinase C by phenylephrine. Perfusion of rabbit hearts with phenylephrine was associated with a positive inotropic response, which was dose and time dependent. Maximal stimulation (1.54-fold increase in +dP/dt) was obtained with 10 microM phenylephrine at 4 minutes. Examination of the activity levels of protein kinase C in these hearts revealed a redistribution of this activity from the cytosolic to the membranous fraction, suggesting the activation of this enzyme in vivo. Prazosin, an alpha 1-adrenergic antagonist, prevented the increase in the inotropy and the redistribution of protein kinase C activity mediated by phenylephrine. Examination of the degree of phosphorylation of membranous, myofibrillar, and cytosolic proteins revealed that activation of protein kinase C in vivo was associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28-kd cytosolic protein. There were no increases in the degree of phosphorylation of phospholamban in the sarcoplasmic reticulum and of troponin I, troponin T, and C protein in the myofibrils, although these proteins were found to be substrates for protein kinase C in vitro. These findings provide evidence that protein kinase C is activated in response to alpha-adrenergic stimulation and that activation is associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28-kd cytosolic protein in the myocardium.
Directional substitution and evolution of nucleotide content in the cytochrome oxidase II gene in earwigs (dermapteran insects) Citation]
Authors: T. Wirth, R. L. Guellec, M. Veuille
Journal: Molecular Biology and Evolution (1999)

The cytochrome oxidase subunit II (COII) gene was sequenced for six dermapteran species. The nucleotide composition of this gene is biased in most animals. While the CG content of other insect orders is low (mean, 27.6%; range, 19.5%-33.1%), species from the Forficula genus showed unusually high values (mean, 42.4%; range, 37.3%-44.1%), mostly due to high CG frequencies at third codon positions: the mean CG content at these positions was around 45% (range, 43.9%-46.9%) for Forficula, compared with only 13.3% for other insects. This effect was so strong that in one species, Forficula lesnei, there was no significant difference between the frequencies of the four bases. During evolution, this loss of bias has involved a significant increase in the synonymous substitution rate and an increase of transitions over transversions compared with other insects. A strong directionality of substitutions has favored T-->C and A-->G changes. This phenomenon was also observed between two conspecific populations of Forficula auricularia. A species from a closely related genus, Anechura bipunctata, was intermediate between Forficula and other insects for these parameters, while two remotely related dermapteran species, Labidura riparia and Euborellia moesta, were similar to other insects. These results suggest that the evolution of Forficula DNA content has been both rapid and recent.
Mechanisms of Antimicrobial Peptide Action and Resistance
Authors: Michael R. Yeaman, Nannette Y. Yount
Journal: Pharmacological Reviews (2003)

Antimicrobial peptides have been isolated and characterized from tissues and organisms representing virtually every kingdom and phylum, ranging from prokaryotes to humans. Yet, recurrent structural and functional themes in mechanisms of action and resistance are observed among peptides of widely diverse source and composition. Biochemical distinctions among the peptides themselves, target versus host cells, and the microenvironments in which these counterparts convene, likely provide for varying degrees of selective toxicity among diverse antimicrobial peptide types. Moreover, many antimicrobial peptides employ sophisticated and dynamic mechanisms of action to effect rapid and potent activities consistent with their likely roles in antimicrobial host defense. In balance, successful microbial pathogens have evolved multifaceted and effective countermeasures to avoid exposure to and subvert mechanisms of antimicrobial peptides. A clearer recognition of these opposing themes will significantly advance our understanding of how antimicrobial peptides function in defense against infection. Furthermore, this understanding may provide new models and strategies for developing novel antimicrobial agents, that may also augment immunity, restore potency or amplify the mechanisms of conventional antibiotics, and minimize antimicrobial resistance mechanisms among pathogens. From these perspectives, the intention of this review is to illustrate the contemporary structural and functional themes among mechanisms of antimicrobial peptide action and resistance.
Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa
Authors: J J Going
Journal: Gut (2002)

Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in dysplastic states but data for oesophageal squamous mucosa and Barrett9s mucosa have not been published. Aim: To test the hypothesis that Mcm proteins are downregulated together with the proliferation marker Ki-67 in differentiating epithelial compartments of non-dysplastic squamous and Barrett9s epithelium, and that this process does not occur in dysplastic mucosae. Methods and cases: Forty five patients with Barrett9s oesophagus included 20 with glandular dysplasia (10 low grade, eight high grade, two both, and four with invasive adenocarcinoma). Twenty five other patients included 12 with oesophageal squamous dysplasia (three low grade, six high grade, three both, and four with invasive squamous carcinoma). Formalin fixed paraffin embedded tissue sections from biopsy series and resections were immunostained using antibodies to Mcm2, Mcm5, and Ki-67. Percentage of nuclei positive for Mcm2, Mcm5, and Ki-67 was estimated and scored from 0 to 6 as: 0, none +; 1, &lt;10%+; 2, 10–30%+; 3, 30–70%+; 4, 70–90%+; 5, &gt;90%+; 6, all+. Four separate epithelial strata were scored: in squamous epithelium the basal layer and thirds to the surface, in Barrett9s mucosa the luminal surface, upper and lower crypt, and deep glands. Results: In non-dysplastic squamous epithelium and Barrett9s mucosa, high level expression of Mcm2, Mcm5, and Ki-67 proteins was largely confined to the proliferative compartments and downregulated in differentiated compartments. Expression persisted up to the mucosal surface in dysplastic squamous epithelium and Barrett9s mucosa. Conclusions: Persistent expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of dysplastic oesophageal squamous epithelium and dysplastic Barrett9s mucosa may be diagnostic markers and imply disruption of cell cycle control and differentiation in these dysplastic epithelia.
Effect of Acute Myocardial Infarction on Electrical Recovery and Transmural Temperature Gradient in Left Ventricular Wall of Dogs
Authors: ERNEST W. REYNOLDS, CONDON R. VANDER ARK, FRANKLIN D. JOHNSTON
Journal: Circulation Research (1960)

Accelerated recovery, as manifested by shortening of the effective refractory period after coronary artery ligation, occurred at either the epicardial or endocardial surface or both in 11 of 13 animals tested with a mean shortening of 15.7 per cent at the epicardial and 13 per cent at the endocardial levels. These changes are attributed to severe anoxia and are believed to be limited to the ischemic area, since studies in the periphery of an infarcted zone show no significant changes in the first 3 hours. In one instance a minor acceleration of recovery was found after 3 hours at the endocardium. All studies showed a final period of delayed recovery. It is felt that this probably reflects a prolonged duration of the membrane action potential during the later stages of myocardial infarction. This is supported by both experimental and human electrocardiographic data which show prolongation of the Q-T interval in association with deeply inverted T waves following the period of acute injury. Transmural temperature studies after coronary artery ligation showed a prompt fall in 2 studies out of 7 and no acute change in the others. Irrigating the pericardial sac with warm Ringer's solution reversed the pre-existing transmural temperature gradient, caused the T waves in epicardial leads to change from negative to positive, and reduced the duration of the effective refractory period at both the endocardial and epicardial surfaces, especially the latter. During the time that the T waves were upright, recovery was completed earlier at the epicardial than at the endocardial surface.
Alterations in Myofilament Function Contribute to Left Ventricular Dysfunction in Pigs Early After Myocardial Infarction
Authors: J. van der Velden, D. Merkus, B.R. Klarenbeek, A.T. James, N.M. Boontje, D.H.W. Dekkers, G.J.M. Stienen, J.M.J. Lamers, D.J. Duncker
Journal: Circulation Research (2004)

Myocardial infarction (MI) initiates cardiac remodeling, depresses pump function, and predisposes to heart failure. This study was designed to identify early alterations in Ca2+ handling and myofilament proteins, which may contribute to contractile dysfunction and reduced beta-adrenergic responsiveness in postinfarct remodeled myocardium. Protein composition and contractile function of skinned cardiomyocytes were studied in remote, noninfarcted left ventricular (LV) subendocardium from pigs 3 weeks after MI caused by permanent left circumflex artery (LCx) ligation and in sham-operated pigs. LCx ligation induced a 19% increase in LV weight, a 69% increase in LV end-diastolic area, and a decrease in ejection fraction from 54+/-5% to 35+/-4% (all P<0.05), whereas cardiac responsiveness to exercise-induced increases in circulating noradrenaline levels was blunted. Endogenous protein kinase A (PKA) was significantly reduced in remote myocardium of MI animals, and a negative correlation (R=0.62; P<0.05) was found between cAMP levels and LV weight-to-body weight ratio. Furthermore, SERCA2a expression was 23% lower after MI compared with sham. Maximal isometric force generated by isolated skinned myocytes was significantly lower after MI than in sham (15.4+/-1.5 versus 19.2+/-0.9 kN/m2; P<0.05), which might be attributable to a small degree of troponin I (TnI) degradation observed in remodeled postinfarct myocardium. An increase in Ca2+ sensitivity of force (pCa50) was observed after MI compared with sham (DeltapCa50=0.17), which was abolished by incubating myocytes with exogenous PKA, indicating that the increased Ca2+ sensitivity resulted from reduced TnI phosphorylation. In conclusion, remodeling of noninfarcted pig myocardium is associated with decreased SERCA2a and myofilament function, which may contribute to depressed LV function. The full text of this article is available online at http://circres.ahajournals.org.
On issues of confidence in determining the time constant for oxygen uptake kinetics
Authors: G H Markovitz, J W Sayre, T W Storer, C B Cooper
Journal: British Journal of Sports Medicine (2004)

TauVO(2 )at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of tauVO(2) with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application.To design a protocol to determine tauVO(2) reliably but simply.On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (VO(2)theta) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. TauVO(2) was determined (a) from the on-transit (on-tauVO(2)) and off-transit (off-tauVO(2)) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-tauVO(2)).Group means (SD) were: VO(2)max 3.84 (0.44) litres/min, VO(2)theta 1.88 (0.23) litres/min, steady state exercise VO(2) 1.67 (0.07) litres/min, on-tauVO(2) 38.0 (5.3) seconds, off-tauVO(2) 39.0 (4.3) seconds, and ramp-tauVO(2) 60.8 (15.4) seconds. On-tauVO(2) correlated with off-tauVO(2) (r = 0.87), VO(2)max (r = -0.73), and VO(2)theta (r = 0.89). The pooled mean tauVO(2) from six superimposed tests agreed with the arithmetic grand mean of the six tests.The average of on-tauVO(2) and off-tauVO(2) fell within the 95% confidence interval of the pooled mean by the second test. Ramp-tauVO(2) was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of tauVO(2), an approach that reduces the number of transitions necessary for accurate determination of tauVO(2), potentially enhancing its clinical application.
Morphometric Age and Mortality After Liver Transplant
Authors: Seth A. Waits, Edward K. Kim, Michael N. Terjimanian, Lindsay M. Tishberg, Calista M. Harbaugh, Kyle H. Sheetz, Christopher J. Sonnenday, June Sullivan, Stewart C. Wang, Michael J. Englesbe
Journal: JAMA Surgery (2014)

Morphometric assessment has emerged as a strong predictor of postoperative morbidity and mortality. However, a gap exists in translating this knowledge to bedside decision making. We introduced a novel measure of patient-centered surgical risk assessment: morphometric age.To investigate the relationship between morphometric age and posttransplant survival.Medical records of recipients of deceased-donor liver transplants (study population) and kidney donors/trauma patients (morphometric age control population).A retrospective cohort study of 348 liver transplant patients and 3313 control patients. We assessed medical records for validated morphometric characteristics of aging (psoas area, psoas density, and abdominal aortic calcification). We created a model (stratified by sex) for a morphometric age equation, which we then calculated for the control population using multivariate linear regression modeling (covariates). These models were then applied to the study population to determine each patient's morphometric age.All analytic steps related to measuring morphometric characteristics were obtained via custom algorithms programmed into commercially available software. An independent observer confirmed all algorithm outputs. Trained assistants performed medical record review to obtain patient characteristics.Cox proportional hazards regression model showed that morphometric age was a significant independent predictor of overall mortality (hazard ratio, 1.03 per morphometric year [95% CI, 1.02-1.04; P < .001]) after liver transplant. Chronologic age was not a significant covariate for survival (hazard ratio, 1.02 per year [95% CI, 0.99-1.04; P = .21]). Morphometric age stratified patients at high and low risk for mortality. For example, patients in the middle chronologic age tertile who jumped to the oldest morphometric tertile have worse outcomes than those who jumped to the youngest morphometric tertile (74.4% vs 93.2% survival at 1 year [P = .03]; 45.2% vs 75.0% at 5 years [P = .03]).Morphometric age correlated with mortality after liver transplant with better discrimination than chronologic age. Assigning a morphometric age to potential liver transplant recipients could improve prediction of postoperative mortality risk.
Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B.
Authors: E J Goetzl, W C Pickett
Journal: The Journal of Experimental Medicine (1981)

A specific 5(S),12(R)-dihydroxy-eicosa-6,8,10(trans/trans/cis), 14(cis)-tetraenoic acid, designated leukotriene B, is generated by the lipoxygenation and subsequent enzymatic hydration of arachidonic acid in a variety of leukocytes. Leukotriene B elicits a maximal human neutrophil chemotactic response in vitro which is similar in magnitude to those evoked by the chemotactic fragment of the fifth component of complement, C5a, synthetic formyl-methionyl peptides, and 5-hydroxy-eicosatetraenoic acid (5-HETE). The neutrophil chemotactic potency of purified leukotriene B, assessed by the 50% effective concentration of 6 x 10(-9) M, is equivalent to that of C5a, but is up to 100-fold greater than that of 5-HETE and of other natural di-HETE isomers. 5(S),12(R)-di-hydroxy-eicosa-6,8,10(all-trans),14(cis)-tetraenoic acid, which differs from leukotriene B only in having a trans-double bond in place of a cis-double bond in the triene portion of the molecule, and acetyl-leukotriene B are significantly less potent neutrophil chemotactic factors than leukotriene B, which indicates that both the conjugated double bonds and the free hydroxyl-group(s) are functionally critical determinants. The capacity of acetyl-leukotriene B to inhibit competitively and selectively the human neutrophil chemotactic response to equimolar concentrations of leukotriene B suggests the existence of a specific subset of receptors for this potent lipid mediator.