tbuckley/cabot-search huggingface dataset:
Reperfusion of Rat Heart After Brief Ischemia Induces Proteolysis of Calspectin (Nonerythroid Spectrin or Fodrin) by Calpain
Authors: Ken-ichi Yoshida, Makoto Inui, Kazuki Harada, Takaomi C. Saido, Yoshihide Sorimachi, Tokuhiro Ishihara, Sei-ichi Kawashima, Kenji Sobue
Journal: Circulation Research (1995)

Abstract Rat myocardium expresses the 240- and 235-kD polypeptides antigenically related to α- and β-subunits of brain calspectin (nonerythroid spectrin or fodrin), respectively. In the subcellular fractions of the myocardium, α-calspectin was found in the 600 g , 10 000 g , and 100 000 g pellets, whereas β-calspectin was localized to the 10 000 g pellet. On the basis of the Na + ,K + -ATPase activity and the contents of a gap junction protein, the sarcolemma was distributed to the 10 000 g and 100 000 g pellets, and the intercalated disks were enriched in the 10 000 g pellet. Both α- and β-calspectin were proteolyzed by calpain in vitro. The two subunits were also proteolyzed in vivo, when the rat hearts underwent 10 to 60 minutes of global ischemia followed by 30 minutes of reperfusion. The reperfusion following the ischemia induced the proteolysis of α-calspectin in the 10 000 g and 100 000 g pellets, producing the 150-kD fragment. A synthetic calpain inhibitor, calpain inhibitor-1, suppressed the degradation of calspectin in vivo, which indicates that calpain is responsible for the reperfusion-induced proteolysis of calspectin. The inhibitor also improved myocardial stunning. Immunohistochemical study revealed that the proteolysis of α-calspectin occurs at the intercalated disks and the sarcolemma after postischemic reperfusion, in accord with the biochemical data. These results suggest that degradation of calspectin partly accounts for the contractile failure of the myocardium after postischemic reperfusion by disrupting the membrane skeleton and the intercalated disks.
A gold standard set of mechanistically diverse enzyme superfamilies.
Authors: Shoshana D Brown, John A Gerlt, Jennifer L Seffernick, Patricia C Babbitt
Journal: Genome biology (2006)

Abstract Superfamily and family analyses provide an effective tool for the functional classification of proteins, but must be automated for use on large datasets. We describe a 'gold standard' set of enzyme superfamilies, clustered according to specific sequence, structure, and functional criteria, for use in the validation of family and superfamily clustering methods. The gold standard set represents four fold classes and differing clustering difficulties, and includes five superfamilies, 91 families, 4,887 sequences and 282 structures.
Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea
Authors: A. Lallas, A. Kyrgidis, T.G. Tzellos, Z. Apalla, E. Karakyriou, A. Karatolias, I. Lefaki, E. Sotiriou, D. Ioannides, G. Argenziano, I. Zalaudek
Journal: British Journal of Dermatology (2012)

Dermoscopy is useful in evaluating skin tumours, but its applicability extends also to the field of inflammatory skin disorders. Plaque psoriasis (PP), dermatitis, lichen planus (LP) and pityriasis rosea (PR) are common inflammatory skin diseases, but little is currently known about their dermoscopic features.To determine and compare the dermoscopic patterns associated with PP, dermatitis, LP and PR and to assess the validity of certain dermoscopic criteria in the diagnosis of PP.Patients with PP, dermatitis, LP and PR were prospectively enrolled. The single most recently developed lesion was examined dermoscopically and histopathologically. Variables included vascular morphology, vascular arrangement, background colour, scale colour, scale distribution and presence of Wickham striae. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves.Eighty-three patients with PP and 86 patients with either dermatitis, LP or PR were included in the study. Dotted vessels in a regular arrangement over a light red background and white scales were highly predictive for the diagnosis of PP, whereas dermatitis more commonly showed yellow scales and dotted vessels in a patchy arrangement. PR was characterized by yellowish background, dotted vessels and peripheral scales; whitish lines (Wickham striae) were seen exclusively in LP.PP, LP, PR and dermatitis show specific dermoscopic patterns that may aid their clinical diagnosis. Certain combinations of dermoscopic features can reliably predict the diagnosis of PP.
In Vivo Magnetic Resonance Imaging of Coronary Thrombosis Using a Fibrin-Binding Molecular Magnetic Resonance Contrast Agent
Authors: René M. Botnar, Arno Buecker, Andrea J. Wiethoff, Edward C. Parsons, Marcus Katoh, George Katsimaglis, Robert M. Weisskoff, Randall B. Lauffer, Philip B. Graham, Rolf W. Gunther, Warren J. Manning, Elmar Spuentrup
Journal: Circulation (2004)

The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis.Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA-labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray-guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 micromol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (approximately 250 micromol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 micromol/L Gd.We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.
Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice
Authors: Helge Frebel, Veronika Nindl, Reto A. Schuepbach, Thomas Braunschweiler, Kirsten Richter, Johannes Vogel, Carsten A. Wagner, Dominique Loffing-Cueni, Michael Kurrer, Burkhard Ludewig, Annette Oxenius
Journal: The Journal of Experimental Medicine (2012)

The inhibitory programmed death 1 (PD-1)–programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1–PD-L1–mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1–deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1–PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell–mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1–PD-L1 pathway protects the vascular system from severe CD8 T cell–mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1–PD-L1 pathway during systemic virus infections.
Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity
Authors: P.J. Perik, B. Rikhof, F.A. de Jong, J. Verweij, J.A. Gietema, W.T.A. van der Graaf
Journal: Annals of Oncology (2007)
The effect of cyclooxygenase inhibition on vasomotion of proximal coronary arteries with endothelial damage.
Authors: G E Lane, A A Bove
Journal: Circulation (1985)

Vasomotion of the proximal branches of the left coronary artery was studied in an intact anesthetized canine preparation after injury to the endothelium of the left anterior descending branch of the left coronary artery (LAD) with a balloon angioplasty catheter. The dimensions of the left coronary artery were examined by quantitative angiography and LAD flow was measured by determining intracoronary 133Xe washout. Thirty minutes after endothelial damage alone dimensions of the LAD remained unchanged. In five dogs continued observation for a total of 120 min revealed no significant change in dimensions of the LAD. In another group of five dogs, after the administration of 5 mg/kg indomethacin there was a progressive reduction in cross-sectional area of the LAD by 60, 90, and 105 min (37%, 42%, and 50%, respectively, p less than .05). No significant change in the dimensions of the undamaged left circumflex artery was noted after the administration of indomethacin. The effect of another cyclooxygenase inhibitor (4 mg/kg meclofenamate) on endothelial damage to the LAD in an additional four dogs was also examined. Again significant reduction of the cross-sectional area of the LAD was seen at 60 and 120 min (40% and 44%, respectively, p less than .05). Heart rate and blood pressure were unchanged throughout the experiment in control and indomethacin-treated dogs. Mean blood pressure rose slightly after administration of meclofenamate (from 80 +/- 5 to 98 +/- 7 at 120 min, p less than .05). These data indicate that the combination of endothelial injury and cyclooxygenase inhibition with indomethacin or meclofenamate results in proximal coronary artery vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Renal Failure after Bilateral Nephrectomy Is Associated with Cytokine-Mediated Pulmonary Injury
Authors: Thomas S. Hoke, Ivor S. Douglas, Christina L. Klein, Zhibin He, Wenfeng Fang, Joshua M. Thurman, Yunxia Tao, Belda Dursun, Norbert F. Voelkel, Charles L. Edelstein, Sarah Faubel
Journal: Journal of the American Society of Nephrology (2006)

Clinical studies demonstrate that acute renal failure (ARF) is associated with increased mortality, which may be due to pulmonary complications. ARF may affect the lung via increased renal production or impaired clearance of mediators of lung injury, such as proinflammatory cytokines. Bilateral nephrectomy is a method to examine directly the deleterious systemic effects of absent renal clearance in ARF without the confounding effects that are associated with ischemia-reperfusion injury (e.g., ischemic ARF) or systemic toxicity (e.g., cisplatin-induced ARF). This study contrasts the effects of ischemic ARF and bilateral nephrectomy on serum cytokines and lung injury. It demonstrates that the acute absence of kidney function after both ischemic ARF and bilateral nephrectomy is associated with an increase in multiple serum cytokines, including IL-6 and IL-1beta, and that the cytokine profiles were distinct. Lung injury after ischemic ARF and bilateral nephrectomy was similar and was characterized by pulmonary vascular congestion and neutrophil infiltration. For investigation of the role of proinflammatory cytokines in pulmonary injury after ARF, the anti-inflammatory cytokine IL-10 was administered before bilateral nephrectomy. IL-10 treatment improved pulmonary architecture and was associated with a reduction in inflammatory markers, including bronchoalveolar lavage fluid total protein, pulmonary myeloperoxidase activity (a biochemical marker of neutrophils), and the chemokine macrophage inflammatory protein 2. These data demonstrate for the first time that the acute absence of kidney function results in pulmonary injury independent of renal ischemia and highlight the critical role of the kidney in the maintenance of serum cytokine balance and pulmonary homeostasis.
Method of Glomerular Filtration Rate Estimation Affects Prediction of Mortality Risk
Authors: Brad C. Astor, Andrew S. Levey, Lesley A. Stevens, Frederick Van Lente, Elizabeth Selvin, Josef Coresh
Journal: Journal of the American Society of Nephrology (2009)

Decreased kidney function, determined using a serum creatinine-based estimation of GFR, is associated with a higher risk for mortality from cardiovascular disease. Equations incorporating cystatin C improve the estimation of GFR, but whether this improves the prediction of risk for mortality is unknown. We measured cystatin C on 6942 adult participants in the Third National Health and Nutrition Examination Survey Linked Mortality File, including all participants who had high serum creatinine (>1.2 mg/dl for men; >1.0 mg/dl for women) or were older than 60 yr and 25% random sample of participants who were younger than 60 yr. We estimated GFR using equations that included standardized serum creatinine, cystatin C, or both. Participant data were linked to the National Death Index. A total of 1573 (22.7%) deaths (713 deaths from cardiovascular disease) occurred during a median of 8 yr. Lower estimated GFR based on cystatin C was strongly associated with higher risk for overall and cardiovascular mortality across the range of normal to moderately decreased estimated GFR. Creatinine-based estimates of GFR resulted in weaker associations, with the association between estimated GFR and all-cause mortality reversed at higher levels of estimated GFR. An equation using both creatinine and cystatin C (in addition to age, race, and gender) resulted in weaker associations than equations using only cystatin C (with or without age, race, and gender). In conclusion, despite better performance in terms of estimating GFR, equations based on both cystatin C and creatinine do not predict mortality as well as equations based on cystatin C alone.
Vector mapping of myocardial activation.
Authors: A H Kadish, J F Spear, J H Levine, R F Hanich, C Prood, E N Moore
Journal: Circulation (1986)

A custom-made probe, consisting of four electrodes arranged so that two orthogonal bipolar electrograms could be recorded from a single site, was used to record epicardial activity during atrial and ventricular pacing in five normal and five anesthetized open-chest mongrel dogs with myocardial infarction. Unfiltered bipolar electrograms recorded with a 2 mm interelectrode distance averaged 36 +/- 15 mV in amplitude and 16 +/- 5 msec in duration in normal areas and 14 +/- 11 mV and 23 +/- 12 msec in infarcted areas (p less than .01 infarct vs normal). The bipolar electrograms were vector summed so that a vector loop could be generated at each site. The direction of epicardial impulse propagation as determined by multipoint isochronal activation mapping was compared with that indicated by maximum x,y deflection of the vector loop. At 203 sites (141 normal and 62 infarcted) there was a median error of only 13 degrees and an excellent correlation by linear regression (r2 = .95). In normal myocardium vector loops were straight (60%), open (21%), or hooked (19%). In infarcted myocardium, notched and irregular loops were occasionally seen. However, a clear maximum x,y deflection was still obtained from 98% of infarcted sites. During ventricular pacing in normal dogs, uniform epicardial conduction was observed for up to 4 cm longitudinal to fiber orientation but only 1 cm transverse to it. At selected sites longitudinal to fiber orientation conduction velocity was 0.618 m/sec, electrogram duration 12 msec, and vector amplitude 76 mV compared with 0.304 m/sec, 18 msec, and 38 mV during conduction transverse to fiber orientation (p less than .05 for all comparisons). Vector mapping of epicardial activation was performed during ventricular tachycardia induced by programmed stimulation in two of five 2-week-old canine myocardial infarcts. Aside from minor irregularities caused by impulse spread around areas of block, vector loops indicated when impulses were spreading away from the area of early epicardial activity and thus directed mapping to the region of earliest activation. We conclude that vector loops generated by summing orthogonal local bipolar electrograms accurately represent the direction of epicardial activation in both normal and infarcted myocardium. Such loops may prove useful in mapping tachycardias and in clarifying details about cardiac activation processes.
Drinking habits as cofactors of risk for alcohol induced liver damage
Authors: S Bellentani, G Saccoccio, G Costa, C Tiribelli, F Manenti, M Sodde, L Saveria Croce’, F Sasso, G Pozzato, G Cristianini, G Brandi and the Dionysos Study Group
Journal: Gut (1997)

Background —The Dionysos Study is a cohort study of the prevalence of chronic liver disease in the general population of two northern Italian communities. It included 6917 subjects, aged 12–65 (69% of the total population). Aims —The aim of this part of the study was to examine the relationship of daily alcohol intake, type of alcoholic beverage consumed, and drinking patterns to the presence of alcohol induced liver damage in an open population. Patients and methods —6534 subjects, free of virus related chronic liver disease and participating in the first cross-sectional part of the study, were fully examined. Each subject underwent: (a) medical history and physical examination, (b) evaluation of alcohol intake using an illustrated dietary questionnaire, and (c) routine blood tests. More invasive diagnostic procedures were performed when indicated. Results —Multivariate analysis showed that the risk threshold for developing either cirrhosis or non-cirrhotic liver damage (NCLD) was ingestion of more than 30 g alcohol per day in both sexes. Using this definition, 1349 individuals (21% of the population studied) were at risk. Of these, only 74 (5.5% of the individuals at risk) showed signs of liver damage. The prevalence of “pure” alcoholic cirrhosis was 0.43% (30 of 6917), representing 2.2% of the individuals at risk, with a ratio of men to women of 9:1, while 44 (3.3% of the individuals at risk) showed persistent signs of NCLD. After 50 years of age, the cumulative risk of developing both NCLD and cirrhosis was significantly higher (p&lt;0.0001) for those individuals who regularly drank alcohol both with and without food than for those who drank only at mealtimes. Conclusions —Our data show that in an open population the risk threshold for developing cirrhosis and NCLD is 30 g ethanol/day, and this risk increases with increasing daily intake. Drinking alcohol outside mealtimes and drinking multiple different alcoholic beverages both increase the risk of developing alcohol induced liver damage.
Effect of inhaled atrial natriuretic peptide and a neutral endopeptidase inhibitor on histamine-induced bronchoconstriction.
Authors: R M Angus, E A Millar, G W Chalmers, N C Thomson
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The reduced ability of inhaled compared with intravenous atrial natriuretic peptide (ANP) to modify bronchial reactivity and tone may be due to degradation of the peptide by neutral endopeptidase (NEP) within the airways. To test this hypothesis, we have examined the effect of thiorphan, an NEP inhibitor, on the protection afforded by inhaled ANP against histamine-induced bronchoconstriction in 10 mildly asthmatic patients. Pretreatment with ANP alone attenuated the bronchoconstrictor response to histamine with a mean (SEM) maximum percent fall in FEV1 after histamine of 15.9 (2.9) (p < 0.05) compared with 24 (2.9) after placebo and 24 (4) after pretreatment with thiorphan alone. Prior inhalation of thiorphan greatly enhanced the ANP effect: the mean maximum percent fall after this combination was 5.1 (2.3) (p < 0.01, compared with ANP alone). Our results suggest that airway NEP is important in modulating the effect of inhaled ANP. It may be possible to exploit the guanylyl cyclase pathway, by which ANP acts, in the treatment of asthma by the administration of ANP analogues stable to neutral endopeptidase.
Modern Contraception: A 1989 Update
Authors: A Rosenfield
Journal: Annual Review of Public Health (1989)

In the 1960s oral contraception was 1st introduced and IUDs were reintroduced; for the 1st time women in developed countries were liberated from the earlier traditional role of repeated child bearing.  Although significant improvements have been made since the 1960s in hormonal and intrauterine contraception very few new contraceptive breakthroughs have been  achieved.  Developments have been hindered by a decrease in contraceptive research by the pharmaceutical industry.  Only 1 major US drug company is currently involved in this area of research as compared with several in the past.  This decreased American interest is a result of the product liability issue in the US and complex regulatory requirements.  As of 1986 156 million couples are protected by sterilization approximately 72% of these being female sterilization.  In the Peoples Republic of China some 59 million women are using IUDs; an additional 24 million women throughout the rest of the world also use this method of birth control.  64 million women are using oral contraceptives; perhaps as many as 200-300 million women have used this method of contraception at 1 time or another over the past 28 years.  This makes oral contraceptives probably the most widely used systemic medication for a preventive purpose in the history of medicine.  At the same time approximately 57% of the some 850-880 million married couples of reproductive age many of them in the developing world are unprotected.  Some of the promising new birth control methods that may be available in the future include new hormonal implants antiprogesterone menses inducers and vaccines.
Gender identity and sport: is the playing field level?: Table 1
Authors: J C Reeser
Journal: British Journal of Sports Medicine (2005)

This review examines gender identity issues in competitive sports, focusing on the evolution of policies relating to female gender verification and transsexual participation in sport. The issues are complex and continue to challenge sport governing bodies, including the International Olympic Committee, as they strive to provide a safe environment in which female athletes may compete fairly and equitably.