tbuckley/cabot-search huggingface dataset:
Inhibition of human platelet aggregation by monovalent antifibrinogen antibody fragments.
Authors: D M Tollefsen, P W Majerus
Journal: Journal of Clinical Investigation (1975)

Monovalent goat antibody fragments (Fab) that were monospecific for human fibrinogen were isolated by affinity chromatography on fibrinogen-Sepharose and used as a direct probe for the involvement of fibrinogen in platelet aggregation and the release reaction. The antifibrinogen Fab inhibited aggregation of washed human platelets induced by thrombin (0.1-10 U/ml) by 50-95%, but had no effect on (14-C)-serotinin release and only a slight inhibitory effect on 125-I-thrombin binding to platelets. Inhibition of aggregation was not observed with nonimmune goat Fab or rabbit antihuman albumie bound tightly at saturation to surface fibrinogen molecules. After washing the platelets once to remove unbound Fab, aggregation by subsequently added thrombin was no longer inhibited. The antifibrinogen Fab inhibited the clotting of fibrinogen by thrombin but did not effect the rate of fibrinopeptide A release, indicating that the Fab inhibits clotting by interfering with the polymerization of fibrin monomers. Our experiments suggest that fibrinogen released from platelets is directly involved in thrombin-induced aggregation of washed platelets, perhaps through polymerization of fibrin monomers generated by proteolytic cleavage of released fibrinogen.
Pulmonary resistance and maximal expiratory flow-rates following isoprenaline in patients with chronic obstructive lung disease
Authors: D. C. Stanescu, J. Clement, K. P. Van De Woestijne
Journal: Thorax (1973)

<b>Stănescu, D. C., Clément, J., and van de Woestijne, K. P. (1973).</b><i>Thorax</i>, <b>28</b>, 716-720. <b>Pulmonary resistance and maximal expiratory flowrates following isoprenaline in patients with chronic obstructive lung disease.</b> Pulmonary resistance, maximal expiratory flowrates (measured from flow-volume curves), and lung volumes were measured in 17 patients with chronic obstructive lung disease before and 20 minutes after isoprenaline aerosols. Forced vital capacity, maximum expiratory flowrates, and pulmonary resistance all changed significantly following isoprenaline. Using a discriminant analysis, we showed that the bronchodilator effect was reflected almost completely by only two indices, pulmonary resistance and maximum expiratory flowrate at 25% of the control vital capacity. The information provided by each was independent. When the change following bronchodilatation is expressed as a percentage, pulmonary resistance carried most of the information and for practical purposes this index may be used alone.
Enhanced Recovery After Surgery: Are We Ready, and Can We Afford Not to Implement These Pathways for Patients Undergoing Radical Cystectomy?
Authors: Hitendra R.H. Patel, Yannick Cerantola, Massimo Valerio, Beata Persson, Patrice Jichlinski, Olle Ljungqvist, Martin Hubner, Wassim Kassouf, Stig Müller, Gabriele Baldini, Francesco Carli, Torvind Naesheim, Lars Ytrebo, Arthur Revhaug, Kristoffer Lassen, Tore Knutsen, Erling Aarsaether, Peter Wiklund, James W.F. Catto
Journal: European Urology (2013)
Contractile endothelin-B (ETB) receptors in human small bronchi
Authors: M Adner, LO Cardell, T Sjoberg, A Ottosson, L Edvinsson
Journal: European Respiratory Journal (1996)

Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
Impact of Unrecognized Myocardial Scar Detected by Cardiac Magnetic Resonance Imaging on Event-Free Survival in Patients Presenting With Signs or Symptoms of Coronary Artery Disease
Authors: Raymond Y. Kwong, Anna K. Chan, Kenneth A. Brown, Carmen W. Chan, H. Glenn Reynolds, Sui Tsang, Roger B. Davis
Journal: Circulation (2006)

Contrast-enhanced cardiac magnetic resonance imaging (CMR) can determine the extent of myocardial scar from infarction (MI). However, the prognostic significance of unrecognized myocardial scar by CMR in patients without a history of MI is unknown.One hundred ninety-five patients without a known prior MI underwent CMR for assessment of left ventricular (LV) function and late gadolinium enhancement (LGE). We assessed the prognostic value of LGE and other CMR variables beyond the strongest clinical predictors and built the best overall models for major adverse cardiac events (MACE) and cardiac mortality. During a median follow-up of 16 months, 31 patients (18%) experienced MACE, including 17 deaths. LGE demonstrated the strongest unadjusted associations with MACE and cardiac mortality (hazard ratios of 8.29 and 10.9, respectively; both P<0.0001). Patients in the lowest tertile of LGE-involved myocardium (mean LV mass, 1.4%) experienced a >7-fold increased risk for MACE. By multivariable analyses, LGE was independently associated with MACE beyond the clinical model (P<0.0001) or the clinical model combined with angiographically significant coronary stenosis (P=0.0007), LV ejection fraction (P=0.001), LV end-systolic volume index (P=0.0006), or segmental WMA (P=0.002). LGE remained the strongest predictor selected in the best overall models for MACE and cardiac mortality.Among patients with a clinical suspicion of coronary artery disease but without a history of MI, LGE involving a small amount of myocardium carries a high cardiac risk. In addition, LGE provides incremental prognostic value to MACE and cardiac mortality beyond common clinical, angiographic, and functional predictors.
Hemodynamic Studies of Patients with Myocardial Infarction
Authors: WARREN W. SMITH, NORMAN S. WIKLER, ARTHUR C. FOX
Journal: Circulation (1954)

Cardiac output, venous and arterial pressure, total peripheral resistance and blood volume were measured in patients with acute myocardial infarction, with and without shock, and on recovery, and in patients without heart disease. Cardiac output falls to below normal after myocardial infarction, and rises significantly, though not always to normal, on recovery. Cardiac output was very low when myocardial infarction was complicated by shock. Fall of cardiac output to very low levels following myocardial infarction does not necessarily lead to development of shock. Venous pressure tended to be elevated in patients in shock as a result of myocardial infarction. Cardiac output was subnormal in patients with arteriosclerosis but without clinical heart disease: this was not attributable to reduced body oxygen consumption.
Effects of high-altitude periodic breathing on sleep and arterial oxyhaemoglobin saturation
Authors: A Salvaggio, G Insalaco, O Marrone, S Romano, A Braghiroli, P Lanfranchi, V Patruno, CF Donner, G Bonsignore
Journal: European Respiratory Journal (1998)

This study aimed to investigate the effect of periodic breathing (PB) at high altitude on sleep structure and arterial oxygen saturation (Sa,O2). Five healthy subjects underwent polysomnographic studies at sea level, and during the first and the fourth week of sojourn at 5,050 m. Their breathing pattern, sleep architecture and Sa,O2 were analysed. PB was detected in the high-altitude studies during nonrapid eye movement (NREM) sleep and tended to increase from the first to the fourth week. Stages 3-4 were absent in four subjects at the first week, but only in one at the fourth week, irrespective of the amount of PB. The arousal index was 11.6+/-3.8 at sea level, 30.1+/-15.5 at the first week at altitude and 33.0+/-18.2 at the fourth week. At altitude, arousal index in NREM sleep was higher during PB than during regular breathing. In NREM sleep, the mean highest Sa,O2 levels in NREM epochs with PB were higher than in those with regular breathing by 2.8+/-1.7% at the first week and 2.9+/-1.5% at the fourth week (p<0.025). From the first to the fourth week, mean Sa,O2 increased significantly during wakefulness (5.6%), NREM (5.2% with regular breathing and 5.3% with PB) and rapid eye movement sleep (7.6%). The data demonstrate a slight role of periodic breathing in altering sleep architecture at high altitude and also show that periodic breathing induces only a minor improvement in arterial oxygen saturation during nonrapid eye movement sleep.
Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate
Authors: E A Carapeti, M A Kamm, P J McDonald, S J D Chadwick, D Melville, R K S Phillips
Journal: Gut (1999)

Topical application of glyceryl trinitrate (GTN) ointment heals chronic anal fissures, providing an alternative to the traditional first line treatment of surgical sphincterotomy.To determine the most effective dose of topical GTN for treatment of chronic anal fissures and to assess long term results.Seventy consecutive patients with chronic anal fissure, were randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%, in a double blind study.After eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). No significant difference was seen between the two active treatments. Headaches were reported by 72% of patients on GTN compared with 27% on placebo (p<0.001). Maximum anal sphincter pressure reduced significantly from baseline by GTN treatment (p=0.02), but not placebo (p=0.8). Mean pain scores were lower after treatment with GTN compared with placebo (NS). Of fissures healed with placebo 43% recurred, compared with 33% of those healed with 0.2% GTN and 25% healed with escalating dose GTN (p=0.7).GTN is a good first line treatment for two thirds of patients with anal fissure. An escalating dose of GTN does not result in earlier healing. Significant recurrence of symptomatic fissures and a high incidence of headaches are limitations of the treatment.
Carbonylation and disassembly of the F-actin cytoskeleton in oxidant induced barrier dysfunction and its prevention by epidermal growth factor and transforming growth factor alpha in a human colonic cell line
Authors: A Banan
Journal: Gut (2000)

Intestinal barrier dysfunction concomitant with high levels of reactive oxygen metabolites (ROM) in the inflamed mucosa have been observed in inflammatory bowel disease (IBD). The cytoskeletal network has been suggested to be involved in the regulation of barrier function. Growth factors (epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha)) protect gastrointestinal barrier integrity against a variety of noxious agents. However, the underlying mechanisms of oxidant induced disruption and growth factor mediated protection remain elusive.To determine: (1) if oxidation and disassembly of actin (a key cytoskeletal component) plays a major role in ROM induced epithelial monolayer barrier dysfunction; and (2) if growth factor mediated protection involves prevention of theses alterations.Caco-2 monolayers were preincubated with EGF, TGF-alpha, or vehicle before incubation with ROM (H(2)O(2) or HOCl). Effects on cell integrity, barrier function, and G- and F-actin (oxidation, disassembly, and assembly) were determined.ROM dose dependently and significantly increased F- and G-actin oxidation (carbonylation), decreased the stable F-actin fraction (index of stability), and increased the monomeric G-actin fraction (index of disassembly). Concomitant with these changes were disruption of the actin cytoskeleton and loss of the monolayer barrier function. In contrast, growth factor pretreatment decreased actin oxidation and enhanced the stable F-actin, while in concert prevented actin disruption and restored normal barrier function of monolayers exposed to ROM. Cytochalasin-D, an inhibitor of actin assembly, not only caused actin disassembly and barrier dysfunction but also abolished the protective action of growth factors. Moreover, an actin stabilising agent, phalloidin, mimicked the protective actions of the growth factors.Oxidation, disassembly, and instability of the actin cytoskeleton appears to play a key role in the mechanism of oxidant induced loss of intestinal barrier integrity. In contrast, organisation and stabilisation of actin through promotion of its assembly plays a critical role in the mechanism of growth factor mediated protection.
Accelerated Evolution of Sex Chromosomes in Aphids, an X0 System
Authors: J. Jaquiery, S. Stoeckel, C. Rispe, L. Mieuzet, F. Legeai, J.-C. Simon
Journal: Molecular Biology and Evolution (2011)

Sex chromosomes play a role in many important biological processes, including sex determination, genomic conflicts, imprinting, and speciation. In particular, they exhibit several unusual properties such as inheritance pattern, hemizygosity, and reduced recombination, which influence their response to evolutionary factors (e.g., drift, selection, and demography). Here, we examine the evolutionary forces driving X chromosome evolution in aphids, an XO system where females are homozygous (XX) and males are hemizygous (X0) at sex chromosomes. We show by simulations that the unusual mode of transmission of the X chromosome in aphids, coupled with cyclical parthenogenesis, results in similar effective population sizes and predicted levels of genetic diversity for X chromosomes and autosomes under neutral evolution. These results contrast with expectations from standard XX/XY or XX/X0 systems (where the effective population size of the X is three-fourths that of autosomes) and have deep consequences for aphid X chromosome evolution. We then localized 52 microsatellite markers on the X and 351 on autosomes. We genotyped 167 individuals with 356 of these loci and found similar levels of allelic richness on the X and on the autosomes, as predicted by our simulations. In contrast, we detected higher dN and dN/dS ratio for X-linked genes compared with autosomal genes, a pattern compatible with either positive or relaxed selection. Given that both types of chromosomes have similar effective population sizes and that the single copy of the X chromosome of male aphids exposes its recessive genes to selection, some degree of positive selection seems to best explain the higher rates of evolution of X-linked genes. Overall, this study highlights the particular relevance of aphids to study the evolutionary factors driving sex chromosomes and genome evolution.
Short repetitive sequences in green algal mitochondrial genomes: potential roles in mitochondrial genome evolution
Authors: A. M. Nedelcu, R. W. Lee
Journal: Molecular Biology and Evolution (1998)

Current data on green algal mitochondrial genomes suggest an unexpected dichotomy within the group with respect to genome structure, organization, and sequence affiliations. The present study suggests that there is a correlation between this dichotomy on one hand and the differences in the abundance, base composition, and distribution of short repetitive sequences we observed among green algal mitochondrial genomes on the other. It is conceivable that the accumulation of GC-rich short repeated sequences in the Chlamydomonas-like but not Prototheca-like mitochondrial genomes might have triggered evolutionary events responsible for the distinct series of evolutionary changes undergone by the two green algal mitochondrial lineages. The similarity in base composition, nucleotide sequence, abundance, and mode of organization we observed between the short repetitive sequences present in Chlamydomonas-like mitochondrial genomes on one hand and fungal and vertebrate homologs on the other might extend to some of the roles that the short repetitive sequences have been shown to have in the latter. Potential involvements we propose for the short repetitive sequences in the evolution of Chlamydomonas-like mitochondrial genomes include fragmentation and scrambling of the ribosomal-RNA-coding regions, extensive gene rearrangements, coding-region deletions, surrogate origins of replication, and chromosomal linearization.
Metacognition may be <i>more</i> impaired than mindreading in autism
Authors: David M. Williams, Sophie E. Lind, Francesca Happé
Journal: Behavioral and Brain Sciences (2009)

Abstract This commentary focuses on evidence from autism concerning the relation between metacognition and mindreading. We support Carruthers' rejection of models 1 (independent systems) and 3 (metacognition before mindreading), and provide evidence to strengthen his critique. However, we also present evidence from autism that we believe supports model 2 (one mechanism, two modes of access) over model 4 (mindreading is prior).
Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation
Authors: Paul J. Egan, Kate E. Lawlor, Warren S. Alexander, Ian P. Wicks
Journal: Journal of Clinical Investigation (2003)

Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of cytokine signaling. To investigate the role of SOCS-1 in regulating inflammatory and immune responses in disease, acute inflammatory arthritis was induced in mice lacking SOCS-1. Expression of SOCS-1 protein was detected within synovial granulomas and pannus tissue of WT mice by day 7 following induction of acute arthritis. The severity of synovial inflammation and joint destruction at the peak of disease was greater in the absence of SOCS-1, although disease resolution occurred normally. There was an increased percentage of myeloid cells infiltrating the synovium in mice lacking SOCS-1, and SOCS-1 promoter activity was present in synovial macrophages, lymphocytes, and fibroblasts, but not granulocytes. The T cell response in draining LNs was also dysregulated, as popliteal LNs from mice lacking SOCS-1 contained approximately fivefold more cells at the peak of acute arthritis. These cells were hyperproliferative on exposure to antigen in vitro, and purified splenic CD4+ T cells from mice lacking SOCS-1 proliferated more strongly in response to stimulation with anti-CD3. Reporter gene expression was detected in CD4+ T cells bearing the activation markers CD25, CD44, and CD69. SOCS-1 is therefore expressed in hematopoietic and nonhematopoietic cell types in vivo and is an important regulator of acute inflammatory arthritis and of CD4+ T cell activation.
Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories
Authors: Xiaoling Wang, Joseph C. Poole, Frank A. Treiber, Gregory A. Harshfield, Coral D. Hanevold, Harold Snieder
Journal: Circulation (2006)

Background— Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. Methods and Results— Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels ( P &lt;0.001) than European Americans and females. Males also showed a greater increase with age ( P &lt;0.001) than females. For nighttime SBP, a faster increase of SBP with age ( P &lt;0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans ( P &lt;0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. Conclusions— We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.
Inspiratory capacity is a new preoperative risk predictor in the patients with lung cancer undergoing surgical resection
Authors: Naozumi Hashimoto, Masaki Matsuo, Noriaki Usami, Kohei Yokoi, Yoshinori Hasegawa
Journal: European Respiratory Journal (2011)

Since surgical complications implicate an enormous economic burden as a result of patient9s unexpected treatments and prolonged postoperative stay (PPS), we face an urgent need to establish preoperative pulmonary assessment to prevent pulmonary complications. We retrospectively evaluated 412 cases of the patients who underwent major lung resection in Nagoya University hospital to determine the new predictor to elucidate the risk for PPS. Chronic obstructive lung disease (COPD), irrespective of the degree of symptoms, was confirmed to be one of the most important risk factors in PPS, for patients with major lung resection. Since mounting evidences suggested that the disease severity of COPD might be strongly associated with inspiratory capacity (IC), we evaluated whether IC, measured by spirometry, could be applied to elucidate the risk for PPS in the patients. The multivariate analysis demonstrated that%IC was one of the most critical and independent risk predictors for PPS. Our data suggested that%IC might be an additional risk predictor for PPS in patients undergoing major lung resection, irrespective of COPD status.
Finger drop in a patient with rheumatoid arthritis
Authors: G. E EHRLICH;, M D SMITH, S P McDONALD
Journal: Annals of the Rheumatic Diseases (1997)

I wish to comment on the case report by McDonald and Smith.1 Although the authors report that a tomographic arthrogram showed no cystic extension of the joint capsule, the two figures are almost identical with those previously seen in antecubital cysts in rheumatoid arthritis.2 These ‘cysts’ are corollaries to the popliteal cysts and are generally …