tbuckley/cabot-search huggingface dataset:
Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein.
Authors: R L Silverstein, L L Leung, P C Harpel, R L Nachman
Journal: Journal of Clinical Investigation (1985)

Thrombospondin (TSP), a multifunctional alpha-granule glycoprotein of human platelets binds fibrinogen, fibronectin, heparin, histidine-rich glycoprotein (HRGP), and plasminogen (Plg), and thus, may play an important role in regulating thrombotic influences at vessel surfaces. In this study we have demonstrated that purified human platelet TSP formed a trimolecular complex with human Plg and HRGP. Complex formation was detected by a specific binding enzyme-linked immunosorbent assay (ELISA) which demonstrated simultaneous binding of fluid-phase Plg and HRGP to TSP adsorbed to microtitration wells. While neither ligand inhibited complex formation of the other with TSP, 10 mM epsilon-amino-n-caproic acid selectively blocked incorporation of Plg into the complex, suggesting that TSP contains independent binding sites for Plg and HRGP. Comparable extent of trimolecular complex formation was also detected when TSP monomer was substituted for whole TSP in the ELISA. HRGP covalently cross-linked to Sepharose 4B simultaneously bound both 125I-TSP and 131I-Plg, confirming trimolecular complex formation. Rocket immunoelectrophoresis of mixtures of the purified radiolabeled proteins into anti-Plg containing agarose also confirmed trimolecular complex formation. The TSP-HRGP-Plg complex bound a similar amount of heparin as the TSP-HRGP complex, demonstrating that the HRGP within the trimolecular complex maintained functional capability. Similarly, using a fluorometric plasmin substrate, the trimolecular complex was shown to be an effective substrate for tissue plasminogen activator. Significant amounts of plasmin were generated from the TSP-HRGP-Plg complex (equivalent to that from the TSP-Plg complex), but the rate of plasmin generation from the trimolecular complex was greater than from the bimolecular complex, suggesting an important interaction of HRGP with Plg when both are complexed to TSP. The macromolecular assembly of these three proteins on cellular surfaces, such as the platelet, may serve important regulatory functions, both prothrombotic at sites of active fibrin deposition and proteolytic in nonfibrin-containing microenvironments.
Effects of Pharyngeal Muscle Activation on Airway Pressure–Area Relationships
Authors: Samuel T. Kuna, Michael J. Brennick
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Fiberoptic imaging in an isolated, sealed upper airway was performed in 10 decerebrate cats to determine the effect of pharyngeal muscle activation on airway pressure-area relationships. Bilateral cuff electrodes stimulated the distal cut ends of the following nerves: medial and lateral hypoglossus, glossopharyngeus, and pharyngeal branch of vagus. At given intraluminal pressures ranging from +6 to -6 cm H2O, cross-sectional area was measured in the rostral oropharynx, velopharynx, and caudal oropharynx, with and without nerve stimulation. A mixed model analysis of variance indicated a relatively constant increase in area across the pressure range with glossopharyngeal stimulation at any given level. Significant interactions between pressure and stimulation were present in the rostral oropharynx with medial hypoglossus stimulation and in the caudal oropharynx with independent and combined hypoglossal branch stimulation and pharyngeal branch of vagus stimulation. With stimulation of the hypoglossal nerves, greater increases in area in these regions occurred in the lower pressure ranges. Stimulation of the pharyngeal branch of the vagus caused a greater decrease in area at the higher pressure ranges in the caudal oropharynx and velopharynx. The results indicate that the mechanical effects of pharyngeal muscle activation depend not only on the region and muscles activated but also on the intraluminal pressure.
Acute Uremia but Not Renal Inflammation Attenuates Aseptic Acute Lung Injury
Authors: Alexander Zarbock, Mirco Schmolke, Tilman Spieker, Kerstin Jurk, Hugo Van Aken, Kai Singbartl
Journal: Journal of the American Society of Nephrology (2006)

Acute renal failure (ARF) remains a major clinical challenge, especially in the intensive care setting. Mortality of ARF combined with acute lung injury (ALI) is even higher and may reach 80%. Recent studies have suggested a remote effect of ARF on pulmonary homeostasis. However, it is unknown whether and to what extent ARF clinically affects pulmonary function, in particular oxygenation. For elucidation of the impact of ARF on aseptic ALI, a murine two-hit model that consists of acute uremia (AU) and subsequent ALI was developed. AU was induced by renal ischemia-reperfusion (inflammatory AU) or bilateral nephrectomy (noninflammatory AU). ALI was initiated by intratracheal HCl instillation and characterized by severe, PMN-dependent decrease in arterial partial pressure of O(2) (>70%) in nonuremic mice. Uremic mice, by contrast, showed a significant protection from ALI (decrease in arterial partial pressure of O(2) <40%); this was independent of the type of AU. Reconstitution experiments, in which uremic neutrophils were injected into nonuremic mice and vice versa, identified uremic neutrophils as the primary mediators. Between normal and uremic neutrophils, there were no differences in apoptosis or superoxide production. Pulmonary recruitment of uremic neutrophils, however, was significantly attenuated compared with that of normal neutrophils. This defect was associated with altered surface expression of L-selectin; sialyl Lewis(x), an L-selectin counterreceptor, previously was proved to be critical in aseptic ALI. In conclusion, it is shown that AU but not renal inflammation attenuates aseptic, neutrophil-dependent ALI and exerts an anti-inflammatory effect by attenuating pulmonary neutrophil recruitment.
Effects of flavonoids derived from Taxus yunnanensis on p-glycoprotein and cytochrome P450 3A4
Authors: Jifu Li, Dake Cai, Huichang Bi, Jing Jin, Min Huang
Journal: Asian Journal of Pharmaceutical Sciences (2013)

The intestinal uptake of paclitaxel is hampered by trans-membrane efflux transporters such as P-glycoprotein (P-gp), and paclitaxel is mainly metabolized by cytochrome P450 3A4 (CYP3A4) presented in the liver. Our previous results demonstrated that flavonoids extracted from Taxus yunnanensis could improve the oral absorption of paclitaxel. The current study was purposed to investigate the effects of the flavonoid extracts on P-gp and CYP3A4 in vitro. The expression and activity of P-gp were detected by western blotting and intracellular rhodamine 123 accumulation assay in Caco-2 cells treated with the flavonoids extract. The expression of CYP3A4 was investigated by western blotting in mouse primary hepatocytes and the activity of CYP3A4 was detected by LC-MS/MS method using rat liver microsomes. Our results showed that the flavonoid extracts from T. yunnanensis could inhibit P-gp activity and concurrently decrease the expression and activity of CYP3A4. In conclusion, activity of P-gp and CYP3A4 could be inhibited by flavonoids extracted from T. yunnanensis which might be potential candidates for development of oral formulation of paclitaxel.
Childhood Antecedents of Exposure to Traumatic Events and Posttraumatic Stress Disorder
Authors: Carla L. Storr, Nicholas S. Ialongo, James C. Anthony, Naomi Breslau
Journal: American Journal of Psychiatry (2007)

Objective: The authors prospectively examined childhood antecedents of exposure to traumatic events to estimate the risk of posttraumatic stress disorder (PTSD) among those exposed to trauma. Method: Two consecutive cohorts of children entering first grade of a public school system in a large mid-Atlantic city in the mid-1980s were followed into young adulthood (mean age=21). Exposure to traumatic events and PTSD were assessed in 75% of the original cohort (N=1,698). Childhood assessments, conducted upon entry into the first grade, included standardized measures of reading readiness, teacher ratings of behavioral problems, and child self-reports about depression and anxiety. Family characteristics were assessed by parental report. Results: Young adults who had been rated by their first grade teacher as having aggressive/disruptive behavior problems were more likely to experience traumatic assaultive violence events (e.g., being mugged/threatened with a weapon, badly beaten-up) (relative risk=2.6) but not PTSD following trauma exposure. Youths with high levels of self-rated depressive and anxious feelings in first grade were more likely to experience PTSD once exposed to trauma (relative risk=1.5). Youths who scored in the highest quartile on a reading test in the first grade were at lower risk for exposure to assaultive violence traumas. Conclusions: Childhood behavioral and depressive/anxious problems may influence the risk for PTSD directly by increasing the vulnerability to the PTSD effects of trauma exposure, and indirectly by increasing the likelihood of exposure to assaultive violence.
Differentiation of Heart Failure Related to Dilated Cardiomyopathy and Coronary Artery Disease Using Gadolinium-Enhanced Cardiovascular Magnetic Resonance
Authors: J.A. McCrohon, J.C.C. Moon, S.K. Prasad, W.J. McKenna, C.H. Lorenz, A.J.S. Coats, D.J. Pennell
Journal: Circulation (2003)

Heart failure treatment depends partly on the underlying cause of the disease. We evaluated cardiovascular magnetic resonance (CMR) for the problem of differentiating dilated cardiomyopathy (DCM) from left ventricular (LV) dysfunction caused by coronary artery disease (CAD).Late gadolinium enhancement with CMR was performed in 90 patients with heart failure and LV systolic dysfunction (63 patients with DCM and unobstructed coronary arteries and 27 with significant CAD at angiography). We also studied 15 control subjects with no coronary risk factors and/or unobstructed coronary arteries. None (0%) of the control subjects had myocardial gadolinium enhancement; however, all patients (100%) with LV dysfunction and CAD had enhancement, which was subendocardial or transmural. In patients with DCM, there were 3 findings: no enhancement (59%); myocardial enhancement indistinguishable from the patients with CAD (13%); and patchy or longitudinal striae of midwall enhancement clearly different from the distribution in patients with CAD (28%).Gadolinium CMR is a powerful technique to distinguish DCM from LV dysfunction related to CAD and yields new insights in DCM. These data suggest that using the coronary angiogram as the arbiter for the presence of LV dysfunction caused by CAD could have lead to an incorrect assignment of DCM cause in 13% of patients, possibly because of coronary recanalization after infarction. The midwall myocardial enhancement in patients with DCM is similar to the fibrosis found at autopsy; it has not previously been visualized in vivo and warrants further investigation. CMR may become a useful alternative to routine coronary angiography in the diagnostic workup of DCM.
Regional myocardial blood flow after sudden aortic constriction in awake dogs.
Authors: A Walston, J C Rembert, J M Fedor, J C Greenfield
Journal: Circulation Research (1978)

Hemodynamic and regional myocardial blood flow responses were studied 5 seconds (early) and 30 seconds (late) after abrupt proximal aortic constriction in chronically instrumented awake dogs. During the early phase, left ventricular end-diastolic pressure (LVEDP) increased and stroke volume (SV) decreased significantly. During the late phase, there was a positive inotropic response manifested by a decrease in LVEDP and increase in SV (Anrep effect). The late inotropic response was closely associated with a recovery from subendocardial underperfusion. Hemodynamic and regional flow responses after beta-adrenergic blockade with propranolol (0.4 mg/kg) were similar to those observed during control. Studies during coronary vasodilation induced by adenosine (0.75--1.0 mg/kg per minute) showed that, if subendocardial flow was elevated during the early phase, the early increase of LVEDP and decrease of SV were less than control; however, if subendocardial flow did not change from control in the early phase and did not subsequently increase, there was no late inotropic response. These data suggest that the Anrep effect in the awake dog is closely related to a recovery from subendocardial ischemia.
Screening for Osteoporosis in Men: A Clinical Practice Guideline from the American College of Physicians
Authors: Amir Qaseem, Vincenza Snow, Paul Shekelle, Robert Hopkins, Mary Ann Forciea, Douglas K. Owens
Journal: Annals of Internal Medicine (2008)

Description: The American College of Physicians developed this guideline to present the available evidence on risk factors and screening tests for osteoporosis in men. Methods: Published literature on this topic was identified by using MEDLINE (1990 to July 2007). Reference mining was done on the retrieved articles, references of previous reviews, and solicited articles from experts. The inclusion criteria for the studies were measuring risk factors for low bone mineral density or osteoporotic fracture in men or comparing 2 different methods of assessment for the presence of osteoporosis in men. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system. Recommendation 1: The American College of Physicians recommends that clinicians periodically perform individualized assessment of risk factors for osteoporosis in older men (Grade: strong recommendation; moderate-quality evidence). Recommendation 2: The American College of Physicians recommends that clinicians obtain dual-energy x-ray absorptiometry for men who are at increased risk for osteoporosis and are candidates for drug therapy (Grade: strong recommendation; moderate-quality evidence). Recommendation 3: The American College of Physicians recommends further research to evaluate osteoporosis screening tests in men.
Inhibitory Roles of Signal Transducer and Activator of Transcription 3 in Antitumor Immunity during Carcinogen-Induced Lung Tumorigenesis
Authors: Shoichi Ihara, Hiroshi Kida, Hisashi Arase, Lokesh P. Tripathi, Yi-An Chen, Tetsuya Kimura, Mitsuhiro Yoshida, Yozo Kashiwa, Haruhiko Hirata, Reiko Fukamizu, Ruriko Inoue, Kana Hasegawa, Sho Goya, Ryo Takahashi, Toshiyuki Minami, Kazuyuki Tsujino, Mayumi Suzuki, Satoshi Kohmo, Koji Inoue, Izumi Nagatomo, Yoshito Takeda, Takashi Kijima, Kenji Mizuguchi, Isao Tachibana, Atsushi Kumanogoh
Journal: Cancer Research (2012)

Abstract Stat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3Δ/Δ) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3Δ/Δ mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3Δ/Δ tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non–small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell–mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis. Cancer Res; 72(12); 2990–9. ©2012 AACR.
Correspondence re R. Lapointe <b> <i>et al</i> </b>., CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells. Cancer Res 2003;63:2836–43.
Authors: Michael von Bergwelt-Baildon, Joachim L. Schultze, Britta Maecker, Isaura Menezes, Lee M. Nadler
Journal: Cancer Research (2004)

CD40-activated B cells (CD40-B cells) have been demonstrated to expand memory and prime naive CD8+ T cells in healthy individuals and cancer patients [(1][1], [2][2], [3][3], [4][4], [5][5], [6)][6] . These findings are of particular interest to the cancer vaccine field because CD40-B cells are
Cabazitaxel Plus Prednisone for Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel: Results from the German Compassionate-use Programme
Authors: Axel Heidenreich, Hans-Jörg Scholz, Sebastian Rogenhofer, Christian Arsov, Margitta Retz, Stefan C. Müller, Peter Albers, Jürgen Gschwend, Manfred Wirth, Ursula Steiner, Kurt Miller, Elmar Heinrich, Lutz Trojan, Björn Volkmer, Friedhelm Honecker, Carsten Bokemeyer, Bastian Keck, Burkhard Otremba, Evelyne Ecstein-Fraisse, David Pfister
Journal: European Urology (2012)
Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus
Authors: F O The, R J Bennink, W M Ankum, M R Buist, O R C Busch, D J Gouma, S van der Heide, R M van den Wijngaard, W J de Jonge, G E Boeckxstaens
Journal: Gut (2007)

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation. Objective: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery. Methods: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT) – computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy. Results: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy. Conclusions: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.
Short-term measurement of catabolic rates using iodine-labeled plasma proteins
Authors: A. S. McFarlane, A. Koj
Journal: Journal of Clinical Investigation (1970)

Fractional catabolic rates of iodine-labeled plasma albumins and fibrinogens have been measured in experiments of a few hours duration in adult rabbits. The method used which is based on release of labeled iodide from the protein gives accurate estimates of catabolic rates (expressed as fractions of the plasma protein pool catabolized per day) after 36 hr without the need for urine collections. At earlier times and using undenatured albumin, fractional catabolic rates increased steadily from approximately 10% per day in the first few hours to a constant 20-25% per day after 24 hr. Fibrinogen values which started at 15% plateaued after 24 hr at 30-35% per day. The fractional synthesis rate of albumin, measured with 14C-labeled carbonate in the first 6 hr when the short-term fractional catabolic rate was 10.2% agreed with the 36 hr plateau value of 29% per day. The presence of traces of denatured or polymerized proteins was revealed by high initial fractional catabolic rates, and in a few experiments biological screening in another animal was not fully effective in removing them. On the other hand, some labeled albumins showed no traces of denatured protein even without biological screening. Fibrinogen polymer was catabolized rapidly and behaved like denatured or incipiently clotted fibrinogen. Irradiation of albumin produced a marked increase in early fractional catabolic rates, and some proteins after prolonged storage and labeling behaved similarly. Alternative theories to explain the low fractional catabolic rates in the first 24 hr are considered. Since radioautographic experiments failed to provide evidence for retention of labeled proteins or their nondiffusible breakdown products inside catabolic cells, preference is given to the view that catabolism occurs in a pool of significant protein content which is either a subunit of the extravascular pool or is independent and sandwiched between the plasma and extravascular pools. Earlier hypotheses concerning small catabolic pools in which protein specific activities approximate closely to plasma values at the same time are considered to be no longer tenable.
Sternoclavicular joint infection as a cause of chest pain.
Authors: P W Seviour, P A Dieppe
Journal: BMJ (1984)

L'articulation sternoclaviculaire est affectee dans 9% des cas d'arthrite septique, mais les signes et symptomes sont mal definis et le diagnostic difficile. Description de 3 cas. Traitement chirurgical efficace: drainage et eventuellement excision d'os necrose, puis antibiotherapie appropriee