tbuckley/cabot-search huggingface dataset:
DISSIMILARITY IN OXYGEN CONSUMPTION BETWEEN THE THORACIC AND ABDOMINAL AORTA IN RATS
Authors: R. W. Christie, L. K. Dahl
Journal: The Journal of Experimental Medicine (1957)

Measurement of oxygen uptake by thoracic and abdominal segments of rat aorta showed significantly lower rates in the abdominal than in the thoracic aorta of adult animals. The evidence suggests that as a rat ages the respiratory rate of abdominal aorta falls more sharply than that of the thoracic segment. This result may provide an explanation for the relatively high incidence of atherosclerosis in abdominal aorta.
Regulation of Phosphoinositide Phospholipases by Hormones, Neurotransmitters, and Other Agonists Linked to G Proteins
Authors: J H Exton
Journal: The Annual Review of Pharmacology and Toxicology (1996)

The actions of many hormones, neurotransmitters, and growth factors are mediated by the hydrolysis of phosphatidylinositol 4,5-bisphosphate catalyzed by specific isozymes of phospholipase C. This hydrolysis releases inositol 1,4,5-trisphosphate, which mobilizes Ca2+ ions from components of the endoplasmic reticulum, and 1,2-diacylglycerol, which activates isozymes of protein kinase C. The hormones and neurotransmitters activate beta-isozymes of phospholipase C through receptors that have seven transmembrane segments and couple to G proteins of the Gq and Gi/o families. Activation of phospholipase C by the Gq family involves their alpha-subunits, whereas activation by the Gi/o family involves their beta gamma-subunits. The growth factors activate gamma-isozymes of phospholipase C through receptors that become autophosphorylated due to their stimulated tyrosine kinase activity and provide binding sites for the Src homology domains of the isozymes. The molecular mechanisms by which agonists activate phopholipase isozymes are described in detail.
Careful operationalization and assessment are critical for advancing the study of the neurobiology of resilience
Authors: Nathan A. Kimbrel, Jean C. Beckham
Journal: Behavioral and Brain Sciences (2015)

Abstract The authors' definition of resilience is too narrow and essentially defines resilience as the absence of psychopathology. Consequently, it is not clear how quantitatively defined resilience differs from quantitatively defined psychopathology according to the authors' definition. We believe the conceptual model would be improved by a broader definition of resilience. There is also a significant need for improved measures of stressor load.
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Authors: G Boden, X Chen, J Ruiz, J V White, L Rossetti
Journal: Journal of Clinical Investigation (1994)

Increased plasma FFA reduce insulin-stimulated glucose uptake. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (approximately 50, approximately 550, approximately 750 microM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (determined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO oxidation) during euglycemic-hyperinsulinemic clamping. Increasing FFA concentration (from approximately 50 to approximately 750 microM) decreased glucose uptake in a dose-dependent fashion (from approximately 9 to approximately 4 mg/kg per min). The decrease was caused mainly (approximately 2/3) by a reduction in glycogen synthesis and to a lesser extent (approximately 1/3) by a reduction in CHO oxidation. We have identified two independent defects in glycogen synthesis. The first consisted of an impairment of muscle glycogen synthase activity. It required high FFA concentration (approximately 750 microM), was associated with an increase in glucose-6-phosphate, and developed after 4-6 h of fat infusion. The second defect, which preceded the glycogen synthase defect, was seen at medium (approximately 550 microM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation. In addition, FFA and/or glycerol increased insulin-suppressed hepatic glucose output by approximately 50%. We concluded that fatty acids caused a dose-dependent inhibition of insulin-stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation) and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level.
Cardiac Actions of Methoxamine
Authors: SHOICHI IMAI, TATSURO SHIGEI, KOROKU HASHIMOTO
Journal: Circulation Research (1961)

The cardiac action of large doses of methoxamine and its antagonistic action to epinephrine were studied, using a dog heart-lung preparation. In doses of 4 mg. and above, methoxamine showed a marked negative inotropic action, while it produced only a slight decrease in the heart rate. Pretreatment of animals with 0.1 mg./Kg. of reserpine did not modify the inotropic action, but the decrease in the heart rate disappeared. Simultaneous with these changes, a decrease in the coronary flow and a rise of the pulmonary arterial pressure were observed. Methoxamine in doses of 1 mg. and more abolished both the positive inotropic and the positive chronotropic actions of epinephrine. The negative inotropic action of methoxamine was ascribed to a nonspecific, as yet undetermined mechanism, and the antagonistic action was ascribed to the competitive antagonism at the receptor site (thus methoxamine may be looked upon as a blocking agent of adrenergic β receptor). The weak negative chronotropic action was taken to be an expression of the blockade of the humoral effects of the intrinsic sympathomimetic amines.
Reduction of Experimental Human Fibrosarcoma Lung Metastasis in Mice by Adenovirus-Mediated Cystatin C Overexpression in the Host
Authors: Charlotte Kopitz, Martina Anton, Bernd Gansbacher, Achim Krüger
Journal: Cancer Research (2005)

Abstract Tumor cell invasion and metastasis are associated with degradation of components of the extracellular matrix by different proteinases. Among those, papain-like cysteine proteases, such as cathepsin B, seem to play an important role, as they are associated with poor clinical outcome in different cancers. In this study, we tested whether cystatin C, a natural extracellular inhibitor of papain-like cysteine proteases, can inhibit metastasis when overexpressed at the tumor-host interface. Local overexpression of cystatin C in liver and lungs of CD1 nu/nu mice was achieved by gene transfer with a novel adenoviral construct, which also led to the presence of 60 ng/mL of cystatin C in the serum. Three days after gene transfer, these mice were challenged by i.v. inoculation of lacZ-tagged human fibrosarcoma cells (HT1080lacZ-K15), leading to the formation of experimental lung and liver metastases. In this model, formation of experimental metastatic foci correlated with expression of cathepsin B in lungs, whereas there was no correlation with metastasis to the liver. In mice overexpressing cystatin C, the number of lung metastases was significantly reduced by 92%, as compared with mice receiving control adenovirus. The efficacy of extravasation of HT1080lacZ-K15 cells into the liver was not affected, indicating the independence of this process from the activity of cysteine-cathepsins. The present report is the first evidence of successful reduction of metastasis by inhibition of cysteine-cathepsins by cystatin C overexpression in the host microenvironment. Furthermore, organ-specific protease expression during tumor-host cell interactions could affect the success of antiproteolytic intervention against metastasis.
Host Stromal Bradykinin B2 Receptor Signaling Facilitates Tumor-Associated Angiogenesis and Tumor Growth
Authors: Yasuhiro Ikeda, Izumi Hayashi, Emi Kamoshita, Akira Yamazaki, Hirahito Endo, Keiko Ishihara, Shohei Yamashina, Yoshiaki Tsutsumi, Hiroaki Matsubara, Masataka Majima
Journal: Cancer Research (2004)

Abstract We evaluated the significance of the host kallikrein-kinin system in tumor angiogenesis and tumor growth using two rodent models genetically deficient in a kallikrein-kinin system. Inoculation of Walker 256 carcinoma cells into the s.c. tissues of the back of normal Brown Norway Kitasato rats (BN-Ki rats) resulted in the rapid development of solid tumors with marked angiogenesis. By contrast, in kininogen-deficient Brown Norway Katholiek rats (BN-Ka rats), which cannot generate intrinsic bradykinin (BK), the weights of the tumors and the extent of angiogenesis were significantly less than those in BN-Ki rats. Daily administration of B2 receptor antagonists significantly reduced angiogenesis and tumor weights in BN-Ki rats to levels similar to those in BN-Ka rats but did not do so in BN-Ka rats. Angiogenesis and tumor growth were significantly suppressed in B2 receptor knockout mice bearing sarcoma 180 compared with their wild-type counterparts. Immunoreactive vascular endothelial growth factor (VEGF) was localized in Walker tumor stroma more extensively in BN-Ki rats than in BN-Ka rats, although immunoreactive B2 receptor also was detected in the stroma to the same extent in both types of rats. Cultured stromal fibroblasts isolated from BN-Ki rats and BN-Ka rats produced VEGF in response to BK (10−8-10−6 m), and this stimulatory effect of BK was abolished with a B2 receptor antagonist, Hoe140 (10−5 m). These results suggest that BK generated from kininogens supplied from the host may facilitate tumor-associated angiogenesis and tumor growth by stimulating stromal B2 signaling to up-regulate VEGF production mainly in fibroblasts.
Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival
Authors: A Baldi
Journal: Thorax (2002)

Background: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. Methods: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21<sup>WAF1/CIP1</sup> (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. Results: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the κ<sup>2</sup> test (p=0.577). A significant positive relationship was found between p21 expression level and the patients9 overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p&lt;0.001). Conclusions: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.
B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Authors: Joel N. H. Stern, Gur Yaari, Jason A. Vander Heiden, George Church, William F. Donahue, Rogier Q. Hintzen, Anita J. Huttner, Jon D. Laman, Rashed M. Nagra, Alyssa Nylander, David Pitt, Sriram Ramanan, Bilal A. Siddiqui, Francois Vigneault, Steven H. Kleinstein, David A. Hafler, Kevin C. O’Connor
Journal: Science Translational Medicine (2014)

In multiple sclerosis patients, B cells mature in the draining cervical lymph nodes before trafficking across the blood-brain barrier.
Sweat rate and fluid turnover in American football players compared with runners in a hot and humid environment
Authors: S Fowkes Godek, A R Bartolozzi, J J Godek
Journal: British Journal of Sports Medicine (2005)

Objectives: To determine sweat rate (SwR) and fluid requirements for American footballers practicing in a hot, humid environment compared with cross country runners in the same conditions. Methods: Fifteen subjects, 10 footballers and five runners, participated. On the 4th and 8th day of preseason two a day practices, SwR during exercise was determined in both morning and afternoon practices/runs from the change in body mass adjusted for fluids consumed and urine produced. Unpaired t tests were used to determine differences between groups. Results: Overall SwR measured in litres/h was higher in the footballers than the cross country runners (2.14 (0.53) v 1.77 (0.4); p&lt;0.01). Total sweat loss in both morning (4.83 (1.2) v 1.56 (0.39) litres) and afternoon (4.8 (1.2) v 1.97 (0.28) litres) practices/runs, and daily sweat losses (9.4 (2.2) v 3.53 (0.54) litres) were higher in the footballers (p&lt;0.0001). The footballers consumed larger volumes of fluid during both morning and afternoon practices/runs (23.9 (8.9) v 5.5 (3.1) ml/min and 23.5 (7.3) v 13.6 (5.6) ml/min; p&lt;0.01). For complete hydration, the necessary daily fluid consumption calculated as 130% of daily sweat loss in the footballers was 12.2 (2.9) litres compared with 4.6 (0.7) litres in the runners (p&lt;0.0001). Calculated 24 hour fluid requirements in the footballers ranged from 8.8 to 19 litres. Conclusions: The American footballers had a high SwR with large total daily sweat losses. Consuming large volumes of hypotonic fluid may promote sodium dilution. Recommendations for fluid and electrolyte replacement must be carefully considered and monitored in footballers to promote safe hydration and avoid hyponatraemia.
Vitamin D and nonalcoholic fatty liver disease (NAFLD): Is it more than just an association?
Authors: Ryan M. Kwok, Dawn M. Torres, Stephen A. Harrison
Journal: Hepatology (2013)

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations. Concomitantly, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. NAFLD and VDD are often found together, and while this is not unexpected, given their similar associations with obesity and sedentary lifestyle, a growing body of evidence points to a closely linked and potentially causative relationship between VDD and NAFLD. The epidemiologic association between VDD and NAFLD as well as the role of VDD in the pathogenesis of NAFLD and the available evidence on the clinical utility of vitamin D replacement in NAFLD populations are discussed.
Survival of Australian lung cancer patients and the impact of distance from and attendance at a thoracic specialist centre: a data linkage study
Authors: Elizabeth Tracey, Brian McCaughan, Tim Badgery-Parker, Jane Young, Bruce Armstrong
Journal: Thorax (2014)

<h3>Background</h3> Lung cancer patients have better survival when treated in thoracic surgical (specialist) centres. <h3>Aims</h3> To determine whether outcome of non-small cell lung cancer (NSCLC) patients is poorer with increasing distance to the nearest accessible specialist hospital (NASH). <h3>Methods</h3> We linked cancer registry, hospital and death records of 23 871 NSCLC patients; 3240 localised, 2435 regional and 3540 distant stage patients hospitalised within 12 months of diagnosis were analysed. Distance from patients’ residences to the NASH was measured using geographical coordinates. Cox proportional hazards models examined predictors of NSCLC death. <h3>Results</h3> Having a resection of the cancer, which admission to a specialist hospital made more likely, substantially reduced hazard of NSCLC death. Distance influenced hazard of death through both these variables; a patient was less likely to be admitted to a specialist hospital than a general hospital and less likely to have a resection the further they lived from the NASH. However, patients who lived distant from the NASH and were admitted to a specialist hospital were more likely to have a resection and less likely to die from NSCLC than patients admitted to a specialist hospital and living closer to the NASH. These patterns varied little with lung cancer stage. <h3>Conclusions</h3> NSCLC outcome is best when patients are treated in a specialist hospital. Greater distance to the NASH can affect its outcome by reducing the likelihood of being treated in a specialist hospital. Research is needed into patient and health service barriers to referral of NSCLC patients for specialist care.
Rupture of a flexor pollicis longus repair in a body builder through the use of an electronic muscle stimulator
Authors: A Ansari, K W D R Ramsey, D C Floyd
Journal: British Journal of Sports Medicine (2006)

Involvement of tendons in hand lacerations is common, and immediate treatment involves exploration and primary repair. A programme of protected rehabilitation to allow healing and prevent rupture must follow. An unusual case is reported of tendon rupture in a body builder caused by use of an electronic muscle stimulator. Body builders should be warned about this mode of rupture, which has not been previously reported, during their rehabilitation.
Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non–Small-Cell Lung Cancer
Authors: Roy S. Herbst, David H. Johnson, Eric Mininberg, David P. Carbone, Ted Henderson, Edward S. Kim, George Blumenschein, Jack J. Lee, Diane D. Liu, Mylene T. Truong, Waun K. Hong, Hai Tran, Anne Tsao, Dong Xie, David A. Ramies, Robert Mass, Somasekar Seshagiri, David A. Eberhard, Sean K. Kelley, Alan Sandler
Journal: Journal of Clinical Oncology (2005)

Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC).A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated. ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months.Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.
Clinical Gastroenterology and Hepatology
Authors: S Ghosh
Journal: Gut (2006)

Edited by W M Weinstein, C J Hawkey, J Bosch. London: Elsevier Mosby, 2005, pp 1191. ISBN 0 323 02751 2

 “We must go beyond textbooks, go out into the bypaths and untrodden depths of the wilderness and travel and explore and tell the world the glories of our journey” Professor John Hope Franklin. 

However, textbooks are changing too. Electronic editions, online extensions, PDA downloadable versions, online updates, and enhancements such as video clips have created a fusion of textbooks and the worldwide web that is changing the experience and expectations of the readership. The emerging pressures of revalidation and recertification of doctors via formal testing is also creating a …
Functional Correlation of Trophinin Expression with the Malignancy of Testicular Germ Cell Tumor
Authors: Shingo Hatakeyama, Chikara Ohyama, Shingo Minagawa, Takamitsu Inoue, Hideaki Kakinuma, Atsushi Kyan, Yoichi Arai, Tomoaki Suga, Jun Nakayama, Tetsuro Kato, Tomonori Habuchi, Michiko N. Fukuda
Journal: Cancer Research (2004)

Abstract Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P &amp;lt; 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-β were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.