tbuckley/cabot-search huggingface dataset:
The hourly rate of urinary amylase excretion, serum amylase, and serum lipase: Part I In control subjects and patients with renal disease
Authors: S. L. Waller, A. J. Ralston
Journal: Gut (1971)

The rates of urinary amylase excretion/hour and the levels of serum amylase and lipase were measured in 190 normal subjects and patients with no evidence of renal or gastrointestinal disorder.The hourly rate of urinary amylase excretion/hour was found to have an upper limit of normal of 69 IU.The upper limit of normal for the serum amylase was 251 IU/litre and for the serum lipase 1.6 units/ml.Raised levels of serum amylase and lipase with a normal rate of urinary amylase excretion/hour were found in chronic renal failure. Part I In control subjects and patients with renal diseaseThe diagnosis of acute and relapsing chronic pan- creatitis may be difficult if a rise in serum amylase which may be transient is missed.The value of determining urinary amylase in the diagnosis of pancreatic disease is not clear, although it has been suggested that the hourly rate of urinary amylase excretion may remain elevated for up to 10 days after an attack of acute pancreatitis (Saxon, Hinkley, Vogel, and Zieve, 1957: Gambill and Mason, 1963).A moderate rise in serum amylase may accompany other acute abdominal conditions, eg, biliary disease, gallstone colic, perforated duodenal ulcer, intestinal obstruction, and ruptured ectopic pregnancy (Kelley, 1957) and may follow upper abdominal sur- gery (Keighley, Johnson, and Stevens, 1969).In addition it is important to know the effect of im- paired renal function on the output of amylase into the urine since acute pancreatitis may be accom- panied by renal insufficiency (Dankner and Heifitz, 1951; Meroney, Lawson, Rubini, and Carbone, 1956; Blainey and Northam, 1967).For a biochemical measurement to be of value in establishing the presence or absence of organic disease it is important to know the normal range and the effect of other diseases on this range.It is also preferable to obtain the blood or urine under clinical rather than experimental conditions.
Effective Gene-Viral Therapy for Telomerase-Positive Cancers by Selective Replicative-Competent Adenovirus Combining with Endostatin Gene
Authors: Qi Zhang, Mingming Nie, Jonathan Sham, Changqing Su, Huibin Xue, Daniel Chua, Weiguo Wang, Zhenfu Cui, Yongjing Liu, Chen Liu, Minghong Jiang, Guoen Fang, Xinyuan Liu, Mengchao Wu, Qijun Qian
Journal: Cancer Research (2004)

Abstract Gene-viral therapy, which uses replication-selective transgene-expressing viruses to manage tumors, can exploit the virtues of gene therapy and virotherapy and overcome the limitations of conventional gene therapy. Using a human telomerase reverse transcriptase-targeted replicative adenovirus as an antiangiogenic gene transfer vector to target new angiogenesis and making use of its unrestrained proliferation are completely new concepts in tumor management. CNHK300-mE is a selective replication transgene-expressing adenovirus constructed to carry mouse endostatin gene therapeutically. Infection with CNHK300-mE was associated with selective replication of the adenovirus and production of mouse endostatin in telomerase-positive cancer cells. Endostatin secreted from a human gastric cell line, SGC-7901, infected with CNHK300-mE was significantly higher than that infected with nonreplicative adenovirus Ad-mE in vitro (800 ± 94.7 ng/ml versus 132.9 ± 9.9 ng/ml) and in vivo (610 ± 42 ng/ml versus 126 ± 13 ng/ml). Embryonic chorioallantoic membrane assay showed that the mouse endostatin secreted by CNHK300-mE inhibited angiogenesis efficiently and also induced distortion of pre-existing vasculature. CNHK300-mE exhibited a superior suppression of xenografts in nude mice compared with CNHK300 and Ad-mE. In summary, we provided a more efficient gene-viral therapy strategy by combining oncolysis with antiangiogenesis.
Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols
Authors: Wesley Greaves, Lianchun Xiao, Beatriz Sanchez-Espiridion, Kranthi Kunkalla, Kunal S Dave, Cynthia S Liang, Rajesh R Singh, Anas Younes, L Jeffrey Medeiros, Francisco Vega
Journal: Journal of Hematology & Oncology (2012)

Abstract Background The mechanisms responsible for chemoresistance in patients with refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confer multidrug resistance in various cancers and ABCC1 overexpression has been shown to contribute to drug resistance in the CHL cell line, KMH2. Findings We analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtained from patients with CHL. All patients received first-line standard chemotherapy with doxorubicin (Adriamycin®), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and was marginally associated with poorer failure-free survival (p = 0.06). Multivariate analysis after adjusting for hemoglobin and albumin levels and age showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028). Conclusions Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
Mechanisms of TGF-β <sub>1</sub> –Induced Intimal Growth
Authors: Goro Otsuka, April Stempien-Otero, Andrew D. Frutkin, David A. Dichek
Journal: Circulation Research (2007)

Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also showed that PAI-1 negatively regulates TGF-beta(1) expression in the artery wall. Here we use plasminogen-deficient mice to test whether TGF-beta(1)-stimulated, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are mediated through inhibition of plasminogen activation by PAI-1. We also use lineage tracing to investigate the origin of cells in TGF-beta(1)-induced intimas. Surprisingly, both TGF-beta(1)-induced, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are independent of plasminogen. Moreover, approximately 50% of cells that migrate into the intima of TGF-beta(1)-overexpressing arteries carry a smooth muscle lineage marker, <1% carry a bone marrow lineage marker, and the remaining cells carry neither marker. Therefore, PAI-1 stimulates intimal growth and suppresses TGF-beta(1) expression through activities other than inhibition of plasminogen activation. In addition, contrary to widely held models, our results do not support a role for plasmin (or thrombospondin) in TGF-beta(1) activation in the artery wall. Further identification of the molecular targets through which PAI-1 stimulates intimal formation and suppresses TGF-beta(1) expression in the artery wall may reveal new approaches for inhibiting intimal formation. Our studies also discount bone marrow as an important source from which TGF-beta(1) recruits intimal cells and suggest instead that TGF-beta(1) induces substantial cell migration either from the adventitia or from an extravascular, but nonhematopoietic source.
Blunted Cytopenias and Weight Loss: New Correlates of Virologic Null Response to Re-treatment of Chronic Hepatitis C
Authors: Karen L Lindsay, Chihiro Morishima, Elizabeth C Wright, Jules L Dienstag, Mitchell L Shiffman, Gregory T Everson, Anna S F Lok, Herbert L Bonkovsky, William M Lee, Timothy R Morgan, Marc G Ghany
Journal: Clinical Gastroenterology and Hepatology (2008)
Reciprocal Regulation of c-Src and STAT3 in Non-Small Cell Lung Cancer
Authors: Lauren Averett Byers, Banibrata Sen, Babita Saigal, Lixia Diao, Jing Wang, Meera Nanjundan, Tina Cascone, Gordon B. Mills, John V. Heymach, Faye M. Johnson
Journal: Clinical Cancer Research (2009)

Signal transducer and activator of transcription-3 (STAT3) is downstream of growth factor and cytokine receptors, and regulates key oncogenic pathways in non-small cell lung cancer (NSCLC). Activation of STAT3 by cellular Src (c-Src) promotes tumor progression. We hypothesized that c-Src inhibition could activate STAT3 by inducing a homeostatic feedback loop, contributing to c-Src inhibitor resistance.The effects of c-Src inhibition on total and phosphorylated STAT3 were measured in NSCLC cell lines and in murine xenograft models by Western blotting. c-Src and STAT3 activity as indicated by phosphorylation was determined in 46 human tumors and paired normal lung by reverse phase protein array. Modulation of dasatinib (c-Src inhibitor) cytotoxicity by STAT3 knockdown was measured by MTT, cell cycle, and apoptosis assays.Depletion of c-Src by small interfering RNA or sustained inhibition by dasatinib increased pSTAT3, which could be blocked by inhibition of JAK. Similarly, in vivo pSTAT3 levels initially decreased but were strongly induced after sustained dasatinib treatment. In human tumors, phosphorylation of the autoinhibitory site of c-Src (Y527) correlated with STAT3 phosphorylation (r = 0.64; P = 2.5 x 10(-6)). STAT3 knockdown enhanced the cytotoxicity of dasatinib.c-Src inhibition leads to JAK-dependent STAT3 activation in vitro and in vivo. STAT3 knockdown enhances the cytotoxicity of dasatinib, suggesting a compensatory pathway that allows NSCLC survival. Data from human tumors showed a reciprocal regulation of c-Src and STAT3 activation, suggesting that this compensatory pathway functions in human NSCLC. These results provide a rationale for combining c-Src and STAT3 inhibition to improve clinical responses.
THE HEDGEHOG PATHWAY AND NEUROLOGICAL DISORDERS
Authors: Tammy Dellovade, Justyna T. Romer, Tom Curran, Lee L. Rubin
Journal: Annual Review of Neuroscience (2006)

The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system, this dual ability is especially important in regulating the behavior of neural stem and progenitor cells. This review summarizes information connecting hedgehog signaling and neural diseases, including neurodegenerative disorders and brain tumors, particularly medulloblastoma. We also describe the discovery and utility of small molecule agonists and antagonists of this pathway and their potential as novel types of therapeutics.
Assessing Iron Overload: Are We There Yet?
Authors: Paul C. Kruger, Michael F. Leahy, John K. Olynyk
Journal: Clinical Cancer Research (2012)

Abstract Iron overload occurs in many hematologic disorders and causes significant morbidity. The advantages of MRI in quantifying liver iron concentration continue to mount, and the association between iron overload and increased mortality after allogeneic stem cell transplant needs further attention. Clin Cancer Res; 18(23); 6395–7. ©2012 AACR.
Small airway dysfunction in asymptomatic bronchial hyperresponsiveness and asthma
Authors: W.‐J. Guan, X.‐Y. Zheng, J.‐P. Zheng, I. M. Boudewijn, E. D. Telenga, E. van der Wiel, T. van der Molen, L. Schiphof, N. H. T. ten Hacken, D. S Postma, M. van den Berge
Journal: Allergy (2014)
Frequent nocturnal awakening in early life is associated with nonatopic asthma in children
Authors: A. L. Kozyrskyj, G. E. Kendall, S. R. Zubrick, J. P. Newnham, P. D. Sly
Journal: European Respiratory Journal (2009)

Sleep deprivation has become a common phenomenon of the Western world and is associated with a variety of medical problems in children. This retrospective longitudinal analysis of a community-based birth cohort was undertaken to determine whether frequent nocturnal awakening during early life was associated with the development of childhood asthma. 2,398 children born to mothers recruited from the antenatal clinics of a single hospital in Perth, Australia during 1989–1991 were followed up at years 1, 2, 3, 6, 8, 10 and 14. Parent-completed questionnaires were analysed. The odds ratio for asthma at age 6 and 14 yrs in children with frequent nocturnal awakening during the first 3 yrs after birth was determined from multiple logistic regression. Following adjustment for asthma risk factors, co-sleeping and family stress, persistent nocturnal awakening was associated with nonatopic asthma at age 6 and 14 yrs (at age 14 yrs: OR 2.18, 95% CI 1.15–4.13) but not with atopic asthma. We found an increased risk of nonatopic asthma in children following frequent nocturnal awakening during the first 3 yrs of life. These hypothesis-generating data suggest the need for further systematic study of the effects of disordered sleep in early life on the development of asthma.
N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design
Authors: L. Scudeller, C. D. Fante, C. Perotti, C. F. Pavesi, D. Coscia, V. Scotti, C. Tinelli
Journal: BMJ (2011)

To investigate the use of a novel study design in analysis of bilateral elbow pain.N of 1, two contemporary arm, open label, randomised controlled clinical trial.A clinical epidemiologist at a university hospital in Pavia, Italy.Two elbows with epicondylitis.Autologous platelet lysate versus "wait and see" strategy.Visual analogue scale for pain on elbow extension and resisted wrist extension.Over six months' follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points).Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs.
Bleeding Is Bad…. Isn’t It?
Authors: Peter B. Berger, Steven V. Manoukian
Journal: Circulation (2007)

A dvances in antithrombin and antiplatelet therapy have traditionally been associated with reductions in myocardial infarction and other thrombotic events in patients who have experienced an acute coronary syndrome (ACS), are undergoing a percutaneous coronary intervention (PCI), or are receiving long-term therapy for secondary prevention of stable vascular disease.Although individual trials of antithrombotic therapy have rarely been able to demonstrate that the reduction in ischemic events leads to a reduction in mortality (the most important end point), meta-analyses have often suggested that this is the case. 1 And because myocardial infarction is an independent correlate of mortality, a link between a reduction in ischemic events and reduced mortality makes intuitive sense.
The Principles of Electro-Therapeutics
Authors: A. H. Bennett
Journal: BMJ (1884)

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Chronic shoulder pain in the community: a syndrome of disability or distress?
Authors: L J Badcock
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: To investigate two questions in a community based population of people with chronic shoulder pain. Firstly, does chronic pain lead to impaired psychological health over time? Secondly, how does restriction of daily activity influence pain perception and psychological health? Methods: Two postal surveys, two years apart, were carried out to identify a group of subjects with chronic shoulder pain. The first survey was sent to a random sample of adults (n=40026) registered with a primary care practice, and included a pain manikin, demographic information, and the Hospital Anxiety and Depression scale (HAD). The second survey was sent to those subjects who reported unilateral shoulder region pain in the first survey and it included a shoulder-specific disability scale, pain severity score, and the HAD. Results: 2606 (65.1%) people responded to the initial survey. Of these, 304 (11.7%) reported unilateral shoulder region pain at baseline. In the subsequent survey, there were 234 responders (83.3% adjusted response): 142 of these reported shoulder pain and formed our study group of "subjects with chronic shoulder pain". Within this group there was no significant change in psychological distress scores between baseline and follow up. Both the disability score and psychological distress scores correlated significantly with pain severity (disability <i>v</i> pain r=0.536, p&lt;0.001; psychological distress <i>v</i> pain r=0.269, p=0.002). When the correlation between disability and pain severity was corrected for possible confounders, it remained significant (r=0.490, p&lt;0.001). This was not the case for the correlation between psychological distress and pain (p&gt;0.05). Disability was significantly correlated with psychological distress on univariate (r=0.445, p&lt;0.001) and multivariate analysis (r=0.341, p=0.002). Conclusion: In those with chronic shoulder pain the relation between pain and psychological health seems to be linked to disability. Psychological distress was not explained by persistent pain itself.
Increased expression of Smad6 deteriorates murine acute experimental pancreatitis in two models
Authors: H Nakamura, M Tashiro, H Asaumi, Y Nomiyama, M Kaku, S Watanabe, T Miyamoto, M Otsuki
Journal: Gut (2008)

<h3>Background:</h3> Smad6 is implicated in the inhibition of bone morphogenetic protein signalling. However, the function of Smad6 in the pancreas remains obscure. <h3>Methods:</h3> To elucidate the unknown function of Smad6, we developed transgenic mice selectively expressing Smad6 in pancreatic acinar cells using a plasmid construct coding rat elastase 1 enhancer/promoter. <h3>Results:</h3> Smad6 transgenic mice had no specific distinguishing phenotype such as body weight, pancreatic wet weight and concentrations of pancreatic protein. However, Smad6 transgenic mice reacted to hyperstimulation by caerulein injection or a diet containing 0.5% ethionine. Maximal amylase release stimulated by CCK-8 was significantly decreased in Smad6 transgenic mice acini, and trypsin activities in transgenic mice acini were significantly increased after stimulation of CCK-8. There was no difference in effect of CCK-8 stimulation on the subsequent increase in intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) between wild-type and transgenic mice acini. These findings suggest that reduced pancreatic enzyme secretion was caused by the disorder of its downstream signal transduction pathways in acinar cells. The amino acid sequence at the N-terminus of Smad6 was similar to that of synaptosome-associated protein (SNAP) 25 interacting protein, which plays an important role in regulating exocytosis of pancreatic enzymes in acinar cells. Pancreatic SNAP25 protein levels in transgenic mice were decreased after caerulein-induced pancreatitis. <h3>Conclusions:</h3> These results suggest that elevated expression of Smad6 inhibits normal function of SNAP25-interacting protein and SNAP25, reduces amylase secretion in acinar cells, and increases the susceptibility of acinar cells to the onset of pancreatitis.
The Ras/Mitogen-Activated Protein Kinase Pathway Inhibitor and Likely Tumor Suppressor Proteins, Sprouty 1 and Sprouty 2 Are Deregulated in Breast Cancer
Authors: Ting Ling Lo, Permeen Yusoff, Chee Wai Fong, Ke Guo, Ben J. McCaw, Wayne A. Phillips, He Yang, Esther Sook Miin Wong, Hwei Fen Leong, Qi Zeng, Thomas Choudary Putti, Graeme R. Guy
Journal: Cancer Research (2004)

Abstract Sprouty (Spry) proteins were found to be endogenous inhibitors of the Ras/mitogen-activated protein kinase pathway that play an important role in the remodeling of branching tissues. We investigated Spry expression levels in various cancers and found that Spry1 and Spry2 were down-regulated consistently in breast cancers. Such prevalent patterns of down-regulation may herald the later application of these isoforms as tumor markers that are breast cancer specific and more profound than currently characterized markers. Spry1 and 2 were expressed specifically in the luminal epithelial cells of breast ducts, with higher expression during stages of tissue remodeling when the epithelial ducts are forming and branching. These findings suggest that Sprys might be involved as a modeling counterbalance and surveillance against inappropriate epithelial expansion. The abrogation of endogenous Spry activity in MCF-7 cells by the overexpression of a previously characterized dominant-negative mutant of Spry, hSpry2Y55F resulted in enhanced cell proliferation in vitro. The hSpry2Y55F stably expressing cells also formed larger and greater number of colonies in the soft-agar assay. An in vivo nude mice assay showed a dramatic increase in the tumorigenic potential of hSpry2Y55F stable cells. The consistent down-regulation of Spry1 and 2 in breast cancer and the experimental evidence using a dominant-negative hSpry2Y55F indicate that Spry proteins may actively maintain tissue integrity that runs amok when their expression is decreased below normal threshold levels. This alludes to a previously unrecognized role for Sprys in cancer development.
Conventional stents versus stents loaded with 125iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial
Authors: Hai-Dong Zhu, Jin-He Guo, Ai-Wu Mao, Wei-Fu Lv, Jian-Song Ji, Wen-Hui Wang, Bin Lv, Rui-Min Yang, Wei Wu, Cai-Fang Ni, Jie Min, Guang-Yu Zhu, Li Chen, Mei-Ling Zhu, Zhen-Yu Dai, Peng-Fei Liu, Jian-Ping Gu, Wei-Xin Ren, Rui-Hua Shi, Gao-Feng Xu, Shi-Cheng He, Gang Deng, Gao-Jun Teng
Journal: The Lancet Oncology (2014)
Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study
Authors: Jie Liu, Furqan Kabir, Jainaba Manneh, Paphavee Lertsethtakarn, Sharmin Begum, Jean Gratz, Steve M Becker, Darwin J Operario, Mami Taniuchi, Lalitha Janaki, James A Platts-Mills, Doris M Haverstick, Mamun Kabir, Shihab U Sobuz, Kaewkanya Nakjarung, Pimmada Sakpaisal, Sasikorn Silapong, Ladaporn Bodhidatta, Shahida Qureshi, Adil Kalam, Queen Saidi, Ndealilia Swai, Buliga Mujaga, Athanasia Maro, Brenda Kwambana, Michel Dione, Martin Antonio, Gibson Kibiki, Carl J Mason, Rashidul Haque, Najeeha Iqbal, Anita K M Zaidi, Eric R Houpt
Journal: The Lancet Infectious Diseases (2014)