tbuckley/cabot-search huggingface dataset:
Effect of A Renal Prostaglandin on Distribution of Blood Flow in the Isolated Canine Kidney
Authors: HAROLD D. ITSKOVITZ, NORBERTO A. TERRAGNO, JOHN C. MCGIFF
Journal: Circulation Research (1974)

In isolated blood-perfused canine kidneys, progressive increases in renal blood flow and its fractional distribution to the inner cortex were correlated with increases in perfusate concentrations of a prostaglandin E-like (PGE-like) substance. The ratio of blood flow to the outer and inner halves of the renal cortex measured by the radioactive-microsphere method changed from 77:23 to 68:32 ( P &lt; 0.001) after 90 minutes of perfusion; simultaneously, the concentration of the PGE-like substance increased from 0.04 ng/ml to 0.59 ng/ml ( P &lt; 0.02). Thus, the greatest rate of increase in the concentration of the PGE-like substance occurred coincidently with the largest increase in inner cortical blood flow, i.e., from 30 ml/min to 69 ml/min ( P &lt; 0.001). During the two subsequent 90-minute perfusion periods, the ratio of outer cortical blood flow to inner cortical blood flow fell to 61:39, and the concentration of the PGE-like substance increased further. When indomethacin was added to the perfusate, the concentration of the PGE-like substance decreased from 1.00 ng/ml to 0.24 ng/ml ( P &lt; 0.05), and renal blood flow decreased, especially in the inner cortex where the decline was from 34% to 19% of total renal blood flow ( P &lt; 0.05). Thus, renal blood flow was redistributed after indomethacin was administered. PGE 2 was infused to determine whether substitution for the loss of circulating PGE-like substance could prevent the effects of indomethacin on the distribution of renal blood flow. Despite administration of exogenous PGE 2 , renal blood flow redistributed after administration of indomethacin, and the ratio of outer cortical blood flow to inner cortical blood flow increased from 68:32 to 80:20 ( P &lt; 0.05). These results suggest that the intrarenal site of synthesis and release of PGE 2 determines its action as a local hormone affecting deep cortical blood flow.
Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.
Authors: H Takikawa, T Beppu, Y Seyama
Journal: Gut (1985)

Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acids and 0.2-1% and 0.3-2% of biliary bile acids respectively. After bile drainage the concentration of serum non-glucuronidated-non-sulphated bile acids decreased more rapidly than glucuronidated and sulphated bile acids. There was little biliary excretion of the glucuronidated and sulphated bile acids. Such conjugation appears to have a role in facilitating bile acid excretion by the urinary route.
Adenovirus-mediated CD40 ligand gene therapy in a rat model of orthotopic hepatocellular carcinoma
Authors: Volker Schmitz, Miguel Barajas, Lin Wang, Dacheng Peng, Marina Duarte, Jesús Prieto, Cheng Qian
Journal: Hepatology (2001)

Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor prognosis. In this study, we have explored a gene–therapeutic approach to stimulate antitumor immunity by adenoviral–mediated transfer of CD40 ligand to treat HCC in rats. In vitro infection of a rat HCC cell line (McA–RH7777) with adenoviral vector expressing CD40 ligand (AdCMVmCD40L) induced CD40L expression in a dose–dependent manner. Expression of CD40L in McA–RH7777 cells did not alter their growth rate in vitro, but it abrogated their tumorigenicity when CD40L–expressing cells were implanted into the liver of syngenic Buffalo rats. In vivo gene therapy of established orthotopic HCC nodules (6.5 mm in diameter) in Buffalo rats by intratumor injection of AdCMVmCD40L vector led to complete tumor eradication and long–term survival in 69.5% of treated animals. Therapy with AdCMVmCD40L induced strong lymphocytic infiltration of the tumoral tissue and increased apoptosis of malignant cells. The observed antitumoral effect was mediated by CD8 + T cells and was associated with increased interleukin (IL)–12 serum levels and enhanced natural killer (NK) activity. Animals that eliminated the tumor after in vivo gene therapy developed protective antitumor immunity being resistant to rechallenge with neoplastic cells. Toxicity of the therapy with AdCMVmCD40L was slight, with only a transient increase in the level of serum transaminases and minor lymphocyte infiltration of normal liver tissue. These data demonstrate that intratumoral administration of AdCMVmCD40L may provide an efficient and safe treatment for HCC.
Effect of an extension tube on the bronchodilator efficacy of terbutaline delivered from a metered dose inhaler.
Authors: S A Gomm, N P Keaney, N J Winsey, T B Stretton
Journal: Thorax (1980)

A double-blind within-patient investigation was performed to determine whether the interposition of an extension tube (10 cm length X 3.2 cm diameter) between a metered dose inhaler and the mouth alters the bronchodilator efficacy of terbutaline sulphate. On two consecutive study days 14 adult patients with stable reversible airways obstruction inhaled a cumulative dose of 500 micrograms of terbutaline which was delivered from a metered dose inhaler with or without the extension tube attached and received placebo in a similar manner. The drug was inhaled in doses of 125, 125, and 250 micrograms at 20 minutes intervals. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), thoracic gas volume (TGV), and specific airways conductance (sGaw). These were done immediately before and at five and 15 minute intervals after each dose, and were repeated 90, 120, 180, 240, and 300 minutes after the first inhalation of terbutaline. Administration of terbutaline with and without an extension tube achieved significant bronchodilation at all dose levels in all respiratory variables (p &lt; 0.001). There was no statistically significant difference in FEV1, FVC, PEFR, and sGaw values at any time or dose level with either method of administration. The use of the extension tube did not impair the efficacy or duration of action of inhaled terbutaline.
Acute cardiac effects of neuregulin-1/ErbB signalling
Authors: F. Rochais, R. Fischmeister
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Neuregulin-1β1 rapidly modulates nitric oxide synthesis and calcium handling in rat cardiomyocytes’ by A. Brero et al ., doi:10.1093/cvr/cvq238

Neuregulin1 (Nrg1) is a member of the epidermal growth factor family. Its biological effects are mediated by the ErbB family of receptor tyrosine kinases (ErbB2, ErbB3, and ErbB4). Nrg1/ErbB signalling is an essential paracrine mediator of cell–cell interactions that are indispensable for cardiac development but also play a crucial role in the adult heart.

In the foetal heart, Nrg1 is produced in the endocardial endothelium adjacent to the cadiomyocytes where the ErbB2 and ErbB4 receptors are expressed. In contrast to ErbB2 and ErbB4, the ErbB3 receptor is only expressed in the mesenchymal cells of the endocardial cushions, the structure that forms the valves.1 The first evidence for a function of the Nrg1/ErbB pathway in cardiac morphogenesis was revealed by studies of mice lacking functional Nrg1, ErbB2, or ErbB4 signalling, which display a similar impairment of cardiac development characterized by a failure to undergo expansion and trabeculation of the primitive ventricles, resulting in embryonic lethality at E10.5.2–4 The similar cardiac phenotypes observed … 

*Corresponding author. Tel: +33 1 46 83 57 71; fax: +33 1 46 83 54 75, Email: rodolphe.fischmeister{at}inserm.fr
High-Throughput Assessment of Cellular Mechanical Properties
Authors: Eric M. Darling, Dino Di Carlo
Journal: Annual Review of Biomedical Engineering (2015)

Traditionally, cell analysis has focused on using molecular biomarkers for basic research, cell preparation, and clinical diagnostics; however, new microtechnologies are enabling evaluation of the mechanical properties of cells at throughputs that make them amenable to widespread use. We review the current understanding of how the mechanical characteristics of cells relate to underlying molecular and architectural changes, describe how these changes evolve with cell-state and disease processes, and propose promising biomedical applications that will be facilitated by the increased throughput of mechanical testing: from diagnosing cancer and monitoring immune states to preparing cells for regenerative medicine. We provide background about techniques that laid the groundwork for the quantitative understanding of cell mechanics and discuss current efforts to develop robust techniques for rapid analysis that aim to implement mechanophenotyping as a routine tool in biomedicine. Looking forward, we describe additional milestones that will facilitate broad adoption, as well as new directions not only in mechanically assessing cells but also in perturbing them to passively engineer cell state.
Augmentation of Endogenous Dopamine Production Increases Lung Liquid Clearance
Authors: Yochai Adir, Zaher S. Azzam, Emilia Lecuona, Sergio Leal, Liuska Pesce, Vidas Dumasius, Alejandro M. Bertorello, Phillip Factor, James B. Young, Karen M. Ridge, Jacob Iasha Sznajder
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We have previously reported that dopamine increased active Na+ transport in rat lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether alveolar epithelial cells produce dopamine and whether increasing endogenous dopamine production by feeding rats a 4% tyrosine diet (TSD) would increase lung liquid clearance. Alveolar Type II cells express the enzyme aromatic-L-amino acid decarboxylase (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L-tyrosine (L-dopa), produce dopamine. Rats fed TSD, a precursor of L-dopa and dopamine, had increased urinary dopamine levels, which were inhibited by benserazide, an inhibitor of AADC. Rats fed TSD for 15, 24, and 48 hours had a 26, 46, and 45% increase in lung liquid clearance, respectively, as compared with controls. Also, dopaminergic D1 receptor antagonist—but not dopaminergic D2 receptor antagonist—inhibited the TSD-mediated increase in lung liquid clearance. Alveolar Type II cells isolated from the lungs of rats after they had been fed TSD for 24 hours demonstrated increased protein abundance of Na,K-ATPase α1 and β1 subunits. Basolateral membranes isolated from peripheral lung tissue of tyrosine-fed rats had increased Na,K-ATPase activity and Na,K-ATPase α1 subunit. These data provide the first evidence that alveolar epithelial cells produce dopamine and that increasing endogenous dopamine increases lung liquid clearance.
Neuroengineering Models of Brain Disease
Authors: Leif H. Finkel
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract The techniques of computational simulation have begun to be applied to modeling neurological disease and mental illness. Such neuroengineering models provide a conceptual bridge between molecular/cellular pathology and cognitive performance. We consider models of Alzheimer's disease, Parkinson's disease, and schizophrenia. Each of these diseases involves a disorder of neuromodulation coupled with underlying neuronal pathology. Parallels arising between these models suggests that a common set of computational mechanisms may account for functional loss across a spectrum of brain diseases. In particular, we focus on attractor-based network dynamics and how they arise from neural architectures, on mechanisms for linking sequences of attractor states and their role in cognition, and on the role of neuromodulation in controlling these processes. These studies suggest new approaches to understanding the forebrain circuits underlying cognition, and point toward a new tool for dissecting the pathophysiology of brain disease.
Morphologic Constitution and Smoking
Authors: Carl C. Seltzer
Journal: JAMA (1963)

<h3>To the Editor:</h3> —As I understand Dr. Flick's letter, his special concern is not with the main essence of my article, namely the presentation of data demonstrating morphological differences between nonsmokers and varieties of smokers, but with the final section entitled "Some Speculations" in which possible implications of the results are projected. Nowhere in my article is there any statement, reference, or implication that, "bodily type, not smoking, is related to lung cancer." In fact, the article specifically states that a determination of a constitutional factor in patients with lung cancer "would not refute the known statistical association between heavy cigarette smoking and death from cancer." Obviously, the individual's constitution is only one element in the complex of factors predisposing to disease. Further support for the constitutional-genetic-host factor is to be seen in the recent
Prostate Cancer Screening; Is This a Teachable Moment?
Authors: O. W. Brawley
Journal: JNCI Journal of the National Cancer Institute (2009)

In this issue of the Journal, Welch and Albertsen ( 1 ) presented information that every man considering prostate cancer screening and treatment should know and understand. Prostate cancer screening has resulted in substantial overdiagnosis and in unnecessary treatment. It may have saved relatively few lives. Results from this article and recent results from prostate cancer screening and prevention trials demand reflection about what we as a society have done and are doing. Lessons to be learned have ethical and economic implications and involve our lack of respect for the scientific process and scientific evidence. As I sat down to write this editorial, I heard a radio commercial that brings perspective to the issue. A local celebrity was promoting prostate cancer awareness. He said, “Prostate cancer is 100% curable when caught early.” He encouraged all men to get screened and announced that a van was touring the area offering screening in supermarket parking lots. This was a community service project sponsored by the radio station, the supermarket chain, and a radiation oncology practice. A commercial like this plays to our fears and prejudices. All of us have been taught from an early age that the best way to deal with cancer is to fi nd it early. With the development of the prostate-specifi c antigen test, prostate cancer screening and early detection efforts surged in the United States in the late 1980s and
Insulin-Like Growth Factor-I Receptor Expression Regulates Neuroblastoma Metastasis to Bone
Authors: Cynthia M. van Golen, Tracy S. Schwab, Bhumsoo Kim, Mary E. Soules, Sang Su Oh, Kevin Fung, Kenneth L. van Golen, Eva L. Feldman
Journal: Cancer Research (2006)

Abstract Neuroblastoma is a pediatric tumor that preferentially metastasizes to bone. Patients with bone metastases have a mortality rate &amp;gt;93%, indicating a need for novel treatment targets. Our laboratory has shown that type I insulin-like growth factor receptor (IGF-IR) expression and activation regulate neuroblastoma cell proliferation, motility, invasion, and survival, and that expression of the IGF-IR correlates with neuroblastoma tumorigenicity. Bone expresses large amounts of IGF ligands, and the IGF system is required for normal bone physiology. The current study addresses the role of the IGF system in neuroblastoma metastasis to bone. Upon reaching the bone marrow through the circulation, neuroblastoma cells must dock at the bone marrow endothelium, extravasate into the bone microenvironment, and destroy bone tissue to allow for tumor growth. This report examines the effects of high IGF-IR expression on neuroblastoma cell interaction with bone. The current data show that neuroblastoma cells with high IGF-IR expression, either endogenously or through transfection, adhere to human bone marrow endothelial cells and subsequently migrate toward both IGF-I and human bone stromal cells. High IGF-IR–expressing neuroblastoma cells adhere tightly to bone stromal cells, flatten, and extend processes. When neuroblastoma cells are injected directly into the tibiae of mice, those cells with increased IGF-IR form both osteolytic lesions within the tibiae and secondary tumors within other sites. These results support the hypothesis that IGF-IR expression in neuroblastoma cells increases tumor cell interaction with the bone microenvironment, resulting in greater formation of metastases.(Cancer Res 2006; 66(13): 6570-8)
Laboratory testing of individuals with severe 1-antitrypsin deficiency in three European centres
Authors: M. Miravitlles, C. Herr, I. Ferrarotti, R. Jardi, F. Rodriguez-Frias, M. Luisetti, R. Bals
Journal: European Respiratory Journal (2010)

α 1 -Antitrypsin (AT) deficiency is a hereditary disorder that may lead to early-onset emphysema, and chronic liver disease later in life. Although there are validated methods for testing, the vast majority of α 1 -AT-deficient individuals remain undiagnosed. Recommendations have been published for the testing and diagnosis of α 1 -AT deficiency; however, guidelines on best practice are not well established. In our article, we review the developments in diagnostic techniques that have taken place in recent years, and describe the practices used in our three European centres. The determination of the level of α 1 -AT and genotyping are reported as the main diagnostic steps, whereas isoelectric focusing (also referred to as phenotyping) is reserved for confirmatory analysis. The following recommendations for best practice are put forward: detection of all PiZZ and other severe deficiency individuals; automated genotyping; preparation of reference standards; quality control programmes; development of standard operating procedure documents; and standardised methods for the collection of dried blood samples. Closer cooperation between laboratories and the sharing of knowledge are recommended, with the objectives of improving the efficiency of the diagnosis of severe α 1 -AT deficiency, increasing the numbers of individuals who are detected with the disorder, and assisting the establishment of new patient identification programmes.
An 'illuminating' CT
Authors: R. H. Westbrook, D. Joshi, A. Prachalias
Journal: Gut (2011)

A 56-year-old man with moderate fibrosis (F4, Ishak Fibrosis Score) secondary to non-alcohol-related fatty liver disease was transferred to our centre for the management of bleeding gastric varices. At the time of his index variceal bleed in June 2008, oesophago-gastro-duodenoscopy (OGD) demonstrated a large bleeding type 2 gastro-oesophageal fundal varix. Haemostasis was achieved with the injection of N-butyl-2-cyanoacrylate (histoacryl glue) and lipoidal and commencement of β blockers. He remained well until March 2010 when he represented with haematemesis. …
Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA (CANUSA) Peritoneal Dialysis Study Group.
Authors: D N Churchill, K E Thorpe, K D Nolph, P R Keshaviah, D G Oreopoulos, D Pagé
Journal: Journal of the American Society of Nephrology (1998)

The objective of this study was to evaluate the association of peritoneal membrane transport with technique and patient survival. In the Canada-USA prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis (CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo after initiation of dialysis; patients were defined as high (H), high average (HA), low average (LA), and low (L) transporters. The Cox proportional hazards method evaluated the association of technique and patient survival with independent variables (demographic and clinical variables, nutrition, adequacy, and transport status). Among 606 patients evaluated by PET, there were 41 L, 192 LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72, and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P = 0.11). The 2-yr probabilities of both patient and technique survival were 86, 61, 52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA, and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33, and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22 for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P < 0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher peritoneal transport is associated with increased risk of either technique failure or death. The decreased drain volume, increased albumin loss, and decreased serum albumin concentration suggest volume overload and malnutrition as mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in H and HA transporters.
Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice
Authors: Xing Xian Yu, Susan F. Murray, Sanjay K. Pandey, Sheri L. Booten, Dingjiu Bao, Xiu‐Zhen Song, Susan Kelly, Songyuan Chen, Robert McKay, Brett P. Monia, Sanjay Bhanot
Journal: Hepatology (2005)

In this study, we investigated the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO). High-fat diet-induced obese (DIO) C57BL/6J mice and ob/ob mice were treated with DGAT2 ASO, control ASO, or saline. DGAT2 ASO treatment reduced DGAT2 messenger RNA (mRNA) levels by more than 75% in both liver and fat but did not change DGAT1 mRNA levels in either of these tissues, which resulted in decreased DGAT activity in liver but not in fat. DGAT2 ASO treatment did not cause significant changes in body weight, adiposity, metabolic rate, insulin sensitivity, or skin microstructure. However, DGAT2 ASO treatment caused a marked reduction in hepatic triglyceride content and improved hepatic steatosis in both models, which was consistent with a dramatic decrease in triglyceride synthesis and an increase in fatty acid oxidation observed in primary mouse hepatocytes treated with DGAT2 ASO. In addition, the treatment lowered hepatic triglyceride secretion rate and plasma triglyceride levels, and improved plasma lipoprotein profile in DIO mice. The positive effects of the DGAT2 ASO were accompanied by a reduction in the mRNA levels of several hepatic lipogenic genes, including SCD1, FAS, ACC1, ACC2, ATP-citrate lyase, glycerol kinase, and HMG-CoA reductase. In conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome.