tbuckley/cabot-search huggingface dataset:
Assessment of Passive Elastic Stiffness for Isolated Heart Muscle and the Intact Heart
Authors: ISRAEL MIRSKY, WILLIAM W. PARMLEY
Journal: Circulation Research (1973)

A sensitive method was developed for detecting stiffness changes in the left ventricle. Stress-strain relationships (σ--ε) were obtained in the form dσ/dε = kσ + c from published studies on eight normal canine hearts, five infarcted canine hearts, and seven isolated cat papillary muscles. Utilizing pressure-volume relationships, the elastic stiffness (dσ/dε) and the stiffness constant ( k ) were also evaluated in patients with normal ventricles, inappropriate hypertrophy, and congestive cardiomyopathy. The k values were 35.0 ± 1.7 (isolated muscle, 30°C), 37.3 ± 1.9 (normal canine, 23°C), and 23.9 (infarcted). For the patient groups, k and the passive elastic stiffness were 15.8 ± 0.3 and 249 ± 22.4 g/cm 2 for 13 normal patients, 26.4 ± 1.7 and 286 ± 32.0 g/cm 2 for 7 patients with inappropriate hypertrophy, and 20.1 ± 1.2 and 1360 ± 209 g/cm 2 for 6 patients with congestive cardiomyopathy. The results indicate that (1) k is sensitive to stiffness changes due to infarction, (2) hypertrophy causes an increase in the value of k although elastic stiffness remains within normal limits, and (3) k for the intact human heart is lower than it is for isolated muscle.
Newborn Size and Body Composition as Predictors of Insulin Resistance and Diabetes in the Parents
Authors: Sargoor R. Veena, Ghattu V. Krishnaveni, Caroline H. Fall
Journal: Diabetes Care (2012)

We aimed to examine detailed neonatal measurements as predictors of later diabetes in both parents.Babies (n = 617) born to nondiabetic parents in Holdsworth Memorial Hospital, Mysore, India, were measured at birth for weight; crown-to-heel length (CHL), crown-to-rump length (CRL), and leg length; skinfolds (triceps and subscapular); and circumferences (head, abdomen, and mid-upper-arm circumference [MUAC]). Nine and a half years later, glucose tolerance and fasting insulin were measured in their parents (469 mothers and 398 fathers).Sixty-two (15.6%) fathers and 22 (4.7%) mothers had developed diabetes. There were linear inverse associations of the children's birth weight, CHL, CRL, MUAC, and skinfolds with paternal diabetes and insulin resistance (P < 0.05 for all). Offspring birth weight and adiposity (MUAC, abdominal circumference, and skinfolds) showed U-shaped associations with maternal diabetes (P for quadratic association <0.05 for all). These associations persisted after adjusting for the parents' current adiposity and maternal glucose concentrations and adiposity during pregnancy. Newborn adiposity was positively related to maternal insulin resistance; this association was nonsignificant after adjusting for maternal current adiposity.Newborn size is a window into the future health of the parents. Small newborn size (especially soft-tissue body components) predicts an increased risk of later diabetes in both parents, suggesting a genetic or epigenetic link between parents' diabetes risk and reduced fetal growth in their children. The association of higher birth weight and newborn adiposity with later maternal diabetes suggests effects on fetal adiposity of the intrauterine environment in prediabetic mothers.
Hydrogen Sulfide as Endothelium-Derived Hyperpolarizing Factor Sulfhydrates Potassium Channels
Authors: Asif K. Mustafa, Gautam Sikka, Sadia K. Gazi, Jochen Steppan, Sung M. Jung, Anil K. Bhunia, Viachaslau M. Barodka, Farah K. Gazi, Roxanne K. Barrow, Rui Wang, L. Mario Amzel, Dan E. Berkowitz, Solomon H. Snyder
Journal: Circulation Research (2011)

Rationale: Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelium-derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H 2 S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. Objective: The purpose of this study was to determine if H 2 S is a major physiological EDHF. Methods and Results: We now show that H 2 S is a major EDHF because in blood vessels of CSE-deleted mice, hyperpolarization is virtually abolished. H 2 S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H 2 S-elicited hyperpolarization. The endothelial intermediate conductance (IK Ca ) and small conductance (SK Ca ) potassium channels mediate in part the effects of H 2 S, as selective IK Ca and SK Ca channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide-insensitive, H 2 S-induced vasorelaxation. Conclusions: H 2 S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S -sulfhydration. Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H 2 S biosynthesis offer therapeutic potential.
The 2010 ACR/EULAR criteria for rheumatoid arthritis: do they affect the classification or diagnosis of rheumatoid arthritis?
Authors: Annette H M van der Helm-van Mil, T W J Huizinga
Journal: Annals of the Rheumatic Diseases (2012)

Rheumatoid arthritis (RA) is diagnosed based on phenotypic characteristics. The 2010 ACR/EULAR criteria were derived with the aim of classifying RA earlier in the disease course than the 1987 ACR criteria. When reviewing thus far published validation studies, it is clear that the 2010 criteria can be fulfilled earlier in time than the 1987 criteria. Therefore, the taskforce that derived the 2010 criteria has succeeded in their main objective. Furthermore, it has been repeatedly shown that the sensitivity of the 2010 criteria is increased compared with the 1987 criteria, but the specificity decreased. As classification criteria aim to arrive at homogeneous groups of patients in order to compare the results of clinical or experimental studies, this decrease in specificity is of concern, as patients with diagnoses other than RA can test positive on the criteria. With regard to diagnosing RA, the overall trend in the data is that early arthritis patients in the rheumatological setting who fulfil the 2010 criteria have a high probability of the disease. Not fulfilling the criteria, in contrast, does not rule out RA in these individuals.
Blockade of B7-H1 and PD-1 by Monoclonal Antibodies Potentiates Cancer Therapeutic Immunity
Authors: Fumiya Hirano, Katsumi Kaneko, Hideto Tamura, Haidong Dong, Shengdian Wang, Masao Ichikawa, Cecilia Rietz, Dallas B. Flies, Julie S. Lau, Gefeng Zhu, Koji Tamada, Lieping Chen
Journal: Cancer Research (2005)

Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.
Prospective comparison of a mobile, unit-use blood gas analysis device with a classical point-of-care blood gas laboratory machine in the daily ICU routine
Authors: Herwig Gerlach, Daniela von Wachsmann, Susanne Toussaint
Journal: European Respiratory Journal (2012)

Technical quality of modern “unit-use” blood gas (BG) analyzers has developed during the last years. In a prospective cohort study, we tested the epoc® device comparing the ABL-800 Flex® machine routinely over 4 weeks in a surgical ICU.  2 nurses took paired BG samples from 8 long-term ventilated patients. Directly measured parameters were: pH, PO 2 , PCO 2 , Na + , K + , Glucose, Lactate, Hct (epoc), and Hb (ABL); calculated parameters: SO 2 , BE, HCO 3  - , Hb (epoc), and Hct (ABL). Confounding factors (course of the study, user, patient) were analyzed. For Na + , K + , and Hb, central lab data were also taken into the analysis. Statistics: t test, Passing-Bablok-Regression, Bland-Altman-Plot, MANOVA.  56 paired samples were analyzed; good accordance was found for K + , Glucose, and Lactate; for pH, a systemic deviation (epoc vs. ABL) was seen (delta MW: +0.03), as well as for Na +  (delta MW: + 5.6); epoc data were nearer to the central lab data compared with the ABL results. For PO 2  and SO 2,  epoc data were lower; similarly epoc PCO 2  was 1,8 mmHg (delta MW) lower as ABL. For one patient, considerably higher Hb values were measured with the epoc device. MANOVA resulted in a low relevance by the user, whereas different patients had a stronger effect.  Although several differences between both devices were significant, the majority of parameters had a good accordance. The strongest delta was seen for Na + , differences for the pH are clinically not relevant. In conclusion, these data demonstrate that both devices deliver comparable results for most blood gas parameters, and thus are considered as equivalent methods in daily ICU practice.
Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints
Authors: N. Busso, V. Peclat, A. So, A.-P. Sappino
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined. <h3>METHODS</h3> Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively. <h3>RESULTS</h3> All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1 (PAI-1) were also increased. <h3>CONCLUSION</h3> Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulting in increased uPA catalytic activity that may play a part in tissue destruction in RA.
J. H. and P. J. CYRIAX “Illustrated Manual of Orthopaedic Medicine”
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1983)

This appears to be the most easily understood book written so far by the 'father' of orthopaedic medicine, profusely illustrated by anatomical drawings made by his wife and numerous photographs in colour showing each stage of exam- ination, massage, manipulation or injection.The first part is devoted to the principles of diagnosis, not only history and static examination, but full and detailed assessment of function, and also of treatment by massage, manipulation or injection.The contraindications of each technique are mentioned, and the indications for leaving conditions alone as they will either resolve spontaneously in a short time or will defy treatment.A full differential diagnosis is given, and warnings propounded for the physician or therapist to be on the look out for malignant or neurological conditions that could present as soft tissue lesions.The next two parts describe soft tissue lesions in the appendicular skeleton and in the spine respectively, both traumatic and degenerative.The specific indications for each form of therapy are given for each condition, with precision.When to inject?-how much, -of what?-how often?-when should the condition be expected to resolve?These details should enable general practitioners as well as rheumatologists and casually surgeons to carry out many procedures with safety and to give a reasonably accurate prognosis.In the section on the spine, traction techniques are included, as well as epidural anaesthesia, but it is hoped that no one will attempt these unless properly instructed!Some physicians will dispute the advisability of Dr. Cyriax' injections into tendons, but he does warn most emphatically the necessity of several weeks local rest afterwards.In his hands, and with his caveats, the precedure seems successful.This is a most valuable and well produced book, not only for the orthopaedic physician, but also of use to all who treat soft tissue lesions, whether in accident and emergency departments, sports injuries clinics, general practice and also physiotherapy and podiatry practices.This book is not designed to replace Dr. Cyriax' 'Textbook of Orthopaedic Medicine', the standard reference book on the subject, but it has a place on the desk for easy and frequent access, as useful in its field for day-to-day consultation as MIMS is for the newly appointed general practitioner.
17 beta-Estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor-dependent mechanism.
Authors: S T Pottratz, T Bellido, H Mocharla, D Crabb, S C Manolagas
Journal: Journal of Clinical Investigation (1994)

We previously reported that 17 beta-estradiol inhibits cytokine-stimulated bioassayable IL-6 and the steady-state level of IL-6 mRNA. To determine the molecular basis of this effect, the transient expression of chloramphenicol acetyltransferase (CAT) reporter plasmid driven by the human IL-6 promoter was studied here in HeLa or murine bone marrow stromal cells (MBA 13.2). 17 beta-estradiol (10(-8) M) completely suppressed stimulated CAT expression in HeLa cells cotransfected with IL-6/CAT constructs and a human estrogen receptor (hER) expression plasmid; but had no effect on reporter expression in HeLa cells not transfected with hER. 17 beta-estradiol also inhibited stimulated expression in MBA 13.2 cells (which express the estrogen receptor constitutively) without the requirement of cotransfection of the hER plasmid. The hormonal effects were indistinguishable between constructs containing a 1.2-kb fragment of the 5' flanking region of the IL-6 gene or only the proximal 225-bp fragment. However, yeast-derived recombinant hER did not bind to the 225-bp segment in DNA band shift assays, nor did the 225-bp fragment compete for binding of an estrogen response element oligonucleotide to yeast-derived estrogen receptor. These data suggest that 17 beta-estradiol inhibits the stimulated expression of the human IL-6 gene through an estrogen receptor mediated indirect effect on the transcriptional activity of the proximal 225-bp sequence of the promoter.
Increased Cardiac Sympathetic Activity and Insulin-Like Growth Factor-I Formation Are Associated With Physiological Hypertrophy in Athletes
Authors: Gian Gastone Neri Serneri, Maria Boddi, Pietro Amedeo Modesti, Ilaria Cecioni, Mirella Coppo, Luigi Padeletti, Antonio Michelucci, Andrea Colella, Giorgio Galanti
Journal: Circulation Research (2001)

Physiological hypertrophy represents the adaptive changes of the heart required for supporting the increased hemodynamic load in regularly trained healthy subjects. Mechanisms responsible for the athlete’s hypertrophy still remain unknown. In 15 trained competitive soccer players and in 15 healthy men not engaged in sporting activities (sedentary control subjects) of equivalent age, we investigated the relationship among cardiac growth factor formation, cardiac sympathetic activity, and left ventricular morphology and function. Cardiac formation of insulin-like growth factor (IGF)-I, endothelin (ET)-1, big ET-1, and angiotensin (Ang) II was investigated at rest by measuring artery-coronary sinus concentration gradients. Cardiac sympathetic activity was studied by [ 3 H]norepinephrine (NE) kinetics. Cardiac IGF-I, but not ET-1, big ET-1, and Ang II, formation was higher in athletes than in control subjects ( P &lt;0.01). NE levels in arterial and peripheral venous blood did not differ between groups. In contrast, coronary sinus NE concentration was higher in athletes than in control subjects ( P &lt;0.01). Cardiac, but not total systemic, NE spillover was also increased in athletes ( P &lt;0.01), whereas cardiac [ 3 H]NE reuptake and clearance were not different. Echocardiographic modifications indicated a volume overload-induced hypertrophy associated with increased myocardial contractility. Multivariate stepwise analysis selected left ventricular mass index as the most predictive independent variable for cardiac IGF-I formation and velocity of circumferential fiber shortening for cardiac NE spillover. In conclusion, increased cardiac IGF-I formation and enhanced sympathetic activity selectively confined to the heart appear to be responsible for the physiological hypertrophy in athletes performing predominantly isotonic exercise.
Human Genetic Data Reveal Contrasting Demographic Patterns between Sedentary and Nomadic Populations That Predate the Emergence of Farming
Authors: Carla Aimé, Guillaume Laval, Etienne Patin, Paul Verdu, Laure Ségurel, Raphaëlle Chaix, Tatyana Hegay, Lluis Quintana-Murci, Evelyne Heyer, Frédéric Austerlitz
Journal: Molecular Biology and Evolution (2013)

Demographic changes are known to leave footprints on genetic polymorphism. Together with the increased availability of large polymorphism data sets, coalescent-based methods allow inferring the past demography of populations from their present-day patterns of genetic diversity. Here, we analyzed both nuclear (20 noncoding regions) and mitochondrial (HVS-I) resequencing data to infer the demographic history of 66 African and Eurasian human populations presenting contrasting lifestyles (nomadic hunter-gatherers, nomadic herders, and sedentary farmers). This allowed us to investigate the relationship between lifestyle and demography and to address the long-standing debate about the chronology of demographic expansions and the Neolithic transition. In Africa, we inferred expansion events for farmers, but constant population sizes or contraction events for hunter-gatherers. In Eurasia, we inferred higher expansion rates for farmers than herders with HVS-I data, except in Central Asia and Korea. Although isolation and admixture processes could have impacted our demographic inferences, these processes alone seem unlikely to explain the contrasted demographic histories inferred in populations with different lifestyles. The small expansion rates or constant population sizes inferred for herders and hunter-gatherers may thus result from constraints linked to nomadism. However, autosomal data revealed contraction events for two sedentary populations in Eurasia, which may be caused by founder effects. Finally, the inferred expansions likely predated the emergence of agriculture and herding. This suggests that human populations could have started to expand in Paleolithic times, and that strong Paleolithic expansions in some populations may have ultimately favored their shift toward agriculture during the Neolithic.
Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas
Authors: J. Feliu, R. Mel, P. Borrega, L. López Gómez, P. Escudero, J. Dorta, J. Castro, S.E. Vázquez-Estévez, M. Bolaños, E. Espinosa, M. González Barón
Journal: Annals of Oncology (2002)
Extracellular ubiquitin inhibits -AR-stimulated apoptosis in cardiac myocytes: role of GSK-3 and mitochondrial pathways
Authors: M. Singh, M. Roginskaya, S. Dalal, B. Menon, E. Kaverina, M. O. Boluyt, K. Singh
Journal: Cardiovascular Research (2009)

Aimsβ-Adrenergic receptor (β-AR) stimulation induces apoptosis in adult rat ventricular myocytes (ARVMs) via the activation of glycogen synthase kinase-3β (GSK-3β) and mitochondrial pathways. However, β-AR stimulation induces apoptosis only in a fraction (∼15–20%) of ARVMs. We hypothesized that ARVMs may secrete/release a survival factor(s) which protects 80–85% of cells from apoptosis.
Increased risk of injury following red and yellow cards, injuries and goals in FIFA World Cups
Authors: Jaakko Ryynänen, Jiri Dvorak, Lars Peterson, Hannu Kautiainen, Jón Karlsson, Astrid Junge, Mats Börjesson
Journal: British Journal of Sports Medicine (2013)

Objective To study the relationship between potentially game-disrupting incidents (PGDIs; red and yellow cards, goals and injuries) and the injury incidence in football. Design Prospective injury surveillance during three FIFA World Cups in 2002, 2006 and 2010. Official match statistics were obtained for all the matches played in the three tournaments. Setting 2002, 2006 and 2010 FIFA World Cups. Participants Team physicians at the 2002, 2006 and 2010 FIFA World Cups. Main outcome measures Injury incidences and incidence rate ratios (IRRs). Results The injury incidence was significantly higher during match periods within the minute of, or during a five-minute period following a yellow card, red card, another injury or a goal (PGDIs) than during other match periods (76.7/1000 match hours; 95% CI (66.6 to 87.9) vs 54.0/1000 match hours (46.9 to 61.9), p&lt;0.001). There were significant differences in injury incidence between different match periods, with the highest injury incidence seen in the last 15 min of the first half (p&lt;0.001). The PGDIs (other than injury) had a tendency to increase towards the end of the game and the most frequent PGDI was a yellow card. There was a risk ratio of 1.17 (95% CI 1.08 to 1.26) for injury, per PGDI (other injuries excluded) (p&lt;0.001), and 1.15 (95% CI 1.06 to 1.24) after adjusted match time (p&lt;0.001). Conclusions The injury incidence is high within the five minutes following a PGDI. For both team management and players, being aware of the increased risk of injury directly after a PGDI may be of clinical relevance, as it may enable them to take precautions in order to prevent injuries. There are significant differences in injury incidence between different match periods and game-related factors, such as PGDIs, appear partly to contribute to this variation.