tbuckley/cabot-search huggingface dataset:
In Memoriam: William H. Daughaday, MD (1918–2013)
Authors: Peter Rotwein
Journal: Endocrine Reviews (2013)

Dr William H. Daughaday, the 51st President of The Endocrine Society, died at age 95 on May 3, 2013. His contributions to endocrinology and to the Society were wide-ranging and numerous, not the least of which was the large cohort of physicians attracted to fundamental and clinical endocrine research by his enthusiasm, energy, and overwhelming intellectual curiosity. Bill Daughaday grew up in greater Chicagoland and attended Harvard College. There he was captain of the wrestling team and was inducted into Phi Beta Kappa. After graduation from Harvard Medical School in 1943, where he was selected for the Alpha Omega Alpha honor society, he served in the Army as a medical officer for 20 months during the latter part of World War II and then returned stateside to continue his clinical and scientific training, initially with Robert H. Williams at Boston City Hospital. In 1947, he moved to Washington University School of Medicine in St Louis as an Assistant Resident in Medicine at Barnes Hospital. He joined the laboratory of Carl and Gerty Cori in 1949 as a Research Fellow and began to investigate the metabolic actions of GH on isolated rat diaphragm. Despite the failure of these studies to explain the (even then) well-known anti-insulin effects of GH, this apparently unpromising exploratory project set into motion a life-long interest in all things GH (1). In 1951, Bill Daughaday formed his own research laboratory and became head of a new Metabolism Division in the Department of Medicine at Washington University (he was acting head in 1950), which he continued to lead for the next 34 years. Under his guidance, the Metabolism Division developed into one of the premier endocrinology units in the country, known for high-level research productivity and superb scientific training, as evidenced by the dozens of former fellows who have occupied leadership positions in academic medicine throughout the world. This drive for excellence was amplified by combined clinical and research activities with the Division of Bone and Mineral Metabolism at neighboring Jewish Hospital of St Louis and with the Division of Endocrinology and Metabolism at St Louis Children’s Hospital. The environment nurtured by Bill guaranteed that trainees
5'-Nucleotidase activity of mouse peritoneal macrophages. I. Synthesis and degradation in resident and inflammatory populations.
Authors: P J Edelson, Z A Cohn
Journal: The Journal of Experimental Medicine (1976)

Mouse resident peritoneal macrophages display sufficient 5'-nucleotidase activity to hydrolyze 58 nm AMP/min per cell protein. This activity increases approximately 163 nm AMP/min per mg after 72 h in culture. The enzyme is renewed in unstimulated cells with a half-time of 13.9 h. The activity is not reduced by treatment of intact cells with a variety of proteolytic enzymes, including trypsin, pronase, urokinase, and plasmin. Cells obtained from an inflammatory exudate have diminished or absent levels of enzyme activity. Endotoxin-elicited cells display enzyme activitiy of 20.9 nm AMP/min per mg, while thioglycollate-stimulated macrophages have no detectable activity. The reduced level of activity in endotoxin-stimulated cells is due to their elevated rate of enzyme degradation, with a half-time of 6.9 h. Their rate of enzyme synthesis is essentially normal. No evidence for latent enzyme activity could be obtained in thioglycollate-stimulated cells, nor do these cells produce any inhibition of normal cell enzyme activity. Serum deprivation reduces the enzyme activity of resident cells to about 45% of control activity. These conditions do not significantly affect the rate of enzyme synthesis, but again are explainable by an increase in the rate of enzyme degradation. Pinocytic rate is elevated in endotoxin-stimulated cells which show a more rapid rate of enzyme degradation than unstimulated cells do. However, in serum-free conditions, the rate of enzyme degradation is doubled with no change in the pinocytic rate of the cells.
Autonomic Nervous System and Benign Essential Hypertension in Man
Authors: JEAN-LOUIS CUCHE, OTTO KUCHEL, ANDRÉ BARBEAU, YVES LANGLOIS, ROGER BOUCHER, JACQUES GENEST
Journal: Circulation Research (1974)

The clinical entity of benign essential hypertension is often subdivided into labile essential hypertension and stable essential hypertension. To establish less arbitrary limits between normotension and labile and stable benign essential hypertension, 70 subjects (56 with benign essential hypertension) were classified according to (a) the usual blood pressure index for each subject and (b) the upper limit of variation of the usual blood pressure indexes of a normotensive population. Catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium were measured in recumbent subjects who had received a controlled-sodium diet. Our findings suggest that (1) benign essential hypertension represents a heterogeneous entity and a continuous spectrum of clinical and biochemical changes when it is related to the level of blood pressure, (2) adrenergic involvement is more evident in labile hypertension, (3) regardless of the urinary excretion of catecholamines in subjects with benign essential hypertension the urinary ratio of dopamine to norepinephrine always remains lower, and (4) a negative correlation exists between urinary sodium excretion and usual blood pressure indexes.
Importance of Functional EGF Receptors in Recovery from Acute Nephrotoxic Injury
Authors: Zoufei Wang, Jian-Kang Chen, Su-wan Wang, Gilbert Moeckel, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2003)

<b>Background and Objective:</b> Evidence for specific physical interventions that improve walking symmetry in individuals with hemiparesis poststroke is limited. The aim of this study was to investigate the rapid and prolonged effects of unilateral step training (UST) on step length asymmetry (SLA) in people with hemiparesis. <b>Subjects and Design:</b> Eighteen individuals with chronic hemiparesis and substantial SLA during overground walking participated in a single-group, pretest-posttest study. The study consisted of 2 phases, with 10 subjects participating in each phase; 2 subjects participated in both phases. <b>Interventions and Measurements:</b> To investigate rapid effects of UST, the participants completed a 20-minute session of UST on a treadmill with their unimpaired limb, with the impaired limb held stationary off the treadmill. Data for spatiotemporal gait parameters during overground walking at self-selected and fastest speeds were collected prior to and following UST, with follow-up measurements at 1 day and 1 week. To investigate the prolonged effects, the participants completed ten 20-minute sessions of UST. Data for spatiotemporal gait parameters were collected prior to training as well as after every third session, with follow-up measurements at 1 and 2 weeks. <b>Results:</b> Immediately following UST, SLA tested during fast-paced overground walking improved by up to 13% (49% reduced to a 36% SLA), with changes retained for up to 24 hours. Following 10 sessions of UST, SLA improved significantly, with changes retained for up to 2 weeks. <b>Limitations:</b> Despite repeated baseline measurements, the absence of a control group was a limitation. Furthermore, stepping characteristics during UST were not quantified. <b>Conclusion:</b> Unilateral step training may improve spatiotemporal patterns in people with substantial gait asymmetry poststroke. Repeated training may be necessary for maintenance of adaptations.
Pulmonary changes induced by trans,trans-2,4-decadienal, a component of cooking oil fumes
Authors: C-K. Wang, L. W. Chang, H. Chang, C-H. Yang, M-H. Tsai, H-T. Tsai, P. Lin
Journal: European Respiratory Journal (2009)

Cooking oil fumes (COF) are known to be associated with respiratory diseases and risk of lung cancer. Involvement of <i>trans</i>,<i>trans</i>-2,4-decadienal (<i>tt</i>-DDE), a major component in COF, is suspected. Male CD-1® (ICR) mice were intratracheally instilled with either 8 or 24 mg·kg<sup>−1</sup><i>tt</i>-DDE weekly for 8 weeks. Total numbers and types of cells in bronchoalveolar lavage fluid (BALF), as well as pathological changes, and inflammatory gene modulations in the lung tissues were assessed. We demonstrated that the number of alveolar macrophages in the BALF was significantly increased in <i>tt</i>-DDE-exposed animals. Histologically, there was a dose-correlated increase in epithelial hyperplasia and granulomatous nodules at the bronchioloalveolar junctions (BAJ). Although both Clara and alveolar type II cells were present in the BAJ lesion, only Clara cells were actively proliferative. However, only alveolar type II cells were found in the BAJ granulomatous nodules. Enhanced accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a known pro-carcinogenic factor, was also detected in many alveolar type II cells at the BAJ lesions. As both BAJ hyperplasia and enhanced pSTAT3 accumulation are known risk factors associated with increased lung adenocarcinoma development, these findings suggest that <i>tt</i>-DDE may pose a risk in lung carcinogenesis.
Src-Dependent Changes in Beta-Catenin Activity Promote a Migratory Phenotype in Endocrine-Resistant Breast Cancer Cells.
Authors: A. Wadhawan, P. Barrett-Lee, C. Smith, R. Nicholson, S. Hiscox
Journal: Cancer Research (2009)

Abstract Background: Acquired resistance to endocrine therapies is associated with disease relapse and progression. In vitro, endocrine resistance is accompanied by increased Src activity and the development of a highly invasive and migratory phenotype. Here we have investigated the role of Src as a modulator of intercellular adhesion in endocrine-resistant breast cancer cells.Methods: Src and beta-catenin expression and activity were determined in endocrine-sensitive MCF7 and T47D cells and tamoxifen-resistant ('TamR') MCF7 cell variants at their basal level and following treatment with the Src inhibitor AZD0530 (0-2µM) using Western Blotting. Cell migration was assessed by seeding cells onto matrix-coated porous membranes in the presence or absence of AZD0530. After 24hrs, migratory cells were fixed, stained and counted. The effects of Src inhibition on beta-catenin association with E-cadherin was measured by immunoprecipitation whilst changes in cell morphology were determined using differential interference contrast microscopy.Results: In contrast to endocrine-sensitive MCF7 cells, tamoxifen-resistant ('TamR') variants displayed high levels of both activated Src kinase (Src phosphorylated at Y419) and tyrosine-phosphorylated beta-catenin (Y142 and Y654). Accompanying this was a decrease in the association of beta-catenin with E-cadherin; TamR cells also grew as dispersed cell colonies and displayed a greatly enhanced migratory phenotype compared to MCF7 cells. Inhibition of Src in TamR cells significantly reduced both Src activity and levels of beta-catenin (Y142 and Y654) whilst restoring beta-catenin association with E-cadherin and suppressing cell migration. Immunohistochemistry studies involving ER+ve breast cancer tissue (n=390 from the ABC trial) have revealed that higher nuclear levels of y142 phosphorylated beta-catenin correlate with increased levels of total beta-catenin in the nuclei, suggesting src activated beta-catenin may confer an aggressive breast cancer phenotype.Treatment of ER+ve, endocrine-sensitive MCF7 and T47D cells with tamoxifen in the short term promoted an increase in Src activity and an accompanying Src-dependent increase in tyrosine-phosphorylated Y142 and Y654 beta-catenin, No effect was seen following treatment with fulvestrant or upon oestrogen deprivation.Conclusion: Src-dependent changes in beta catenin phosphorylation status appear to play a central role in the development of the migratory nature accompanying tamoxifen resistance in breast cancer cells which may correlate with findings in clinical tissue. Importantly, Src-dependent changes in beta-catenin activity appear to be promoted by tamoxifen itself during the drug-responsive phase and can be suppressed by the concomitant use of Src inhibitors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5143.
Associations Between End-of-Life Discussion Characteristics and Care Received Near Death: A Prospective Cohort Study
Authors: Jennifer W. Mack, Angel Cronin, Nancy L. Keating, Nathan Taback, Haiden A. Huskamp, Jennifer L. Malin, Craig C. Earle, Jane C. Weeks
Journal: Journal of Clinical Oncology (2012)

Purpose National guidelines recommend that discussions about end-of-life (EOL) care planning happen early for patients with incurable cancer. We do not know whether earlier EOL discussions lead to less aggressive care near death. We sought to evaluate the extent to which EOL discussion characteristics, such as timing, involved providers, and location, are associated with the aggressiveness of care received near death. Patients and Methods We studied 1,231 patients with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a population- and health system–based prospective cohort study, who died during the 15-month study period but survived at least 1 month. Our main outcome measure was the aggressiveness of EOL care received. Results Nearly half of patients received at least one marker of aggressive EOL care, including chemotherapy in the last 14 days of life (16%), intensive care unit care in the last 30 days of life (9%), and acute hospital-based care in the last 30 days of life (40%). Patients who had EOL discussions with their physicians before the last 30 days of life were less likely to receive aggressive measures at EOL, including chemotherapy (P = .003), acute care (P &lt; .001), or any aggressive care (P &lt; .001). Such patients were also more likely to receive hospice care (P &lt; .001) and to have hospice initiated earlier (P &lt; .001). Conclusion Early EOL discussions are prospectively associated with less aggressive care and greater use of hospice at EOL.
Mechanism of the Inhibitory Effect of OPB-9195 [(±)-2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide] on Advanced Glycation End Product and Advanced Lipoxidation End Product Formation
Authors: TOSHIO MIYATA, YASUHIKO UEDA, KOICHI ASAHI, YUKO IZUHARA, REIKO INAGI, AKIRA SAITO, CHARLES VAN YPERSELE DE STRIHOU, KIYOSHI KUROKAWA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The accumulation in uremic plasma of reactive carbonyl compounds (RCO) derived from both carbohydrates and lipids (“carbonyl stress”) contributes to uremic toxicity by accelerating the advanced glycation and lipoxidation of proteins. It was previously demonstrated that OPB-9195 [(±)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide] inhibited the in vitro formation of advanced glycation end products (AGE) in uremic plasma. This study was designed to elucidate the mechanism of action of OPB-9195 by further delineating the AGE and advanced lipoxidation end product (ALE) precursors targeted by this drug. The inhibitory effects of OPB-9195 on the formation of two AGE ( N ε-carboxymethyllysine and pentosidine) on bovine serum albumin incubated with various AGE precursors were examined. Inhibition of N ε-carboxymethyllysine and pentosidine formation with OPB-9195 was more efficient than with aminoguanidine. OPB-9195 also proved effective in blocking the carbonyl amine chemical processes involved in the formation of two ALE (malondial-dehyde-lysine and 4-hydroxynonenal-protein adduct). The efficiency of OPB-9195 was similar to that of aminoguanidine. When glucose-based peritoneal dialysis fluid was incubated in the presence of OPB-9195, a similar inhibition of AGE formation was observed. The direct effect of OPB-9195 on major glucose-derived RCO in peritoneal dialysis fluids was then evaluated. The effects of OPB-9195 could be accounted for by its ability to trap RCO. The concentrations of three major glucose-derived RCO (glyoxal, methylglyoxal, and 3-deoxy-glucosone) were significantly lower in the presence of OPB-9195 than in its absence. Aminoguanidine had a similar effect. In conclusion, OPB-9195 inhibits both AGE and ALE formation, probably through its ability to trap RCO. OPB-9195 might prove to be a useful tool to inhibit some of the effects of RCO-related uremic toxicity.
Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C
Authors: Davide Bitetto, Giovanna Fattovich, Carlo Fabris, Elisa Ceriani, Edmondo Falleti, Ezio Fornasiere, Michela Pasino, Donatella Ieluzzi, Annarosa Cussigh, Sara Cmet, Mario Pirisi, Pierluigi Toniutto
Journal: Hepatology (2011)

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups—C/C homozygotes with vitamin D levels &gt;20 ng/mL (group A) or ≤20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels &gt;20 ng/mL (group C) or ≤20 ng/mL (group D)—a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) ( P &lt; 0.0001). Conclusion: Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;)
Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression
Authors: C Bourgier
Journal: Gut (2005)

<b>Background:</b> Late radiation enteritis in humans is associated with accumulation of extracellular matrix and increased connective tissue growth factor (CTGF) expression that may involve intestinal muscular layers. <b>Aims:</b> We investigated the molecular pathways involved in maintenance of radiation induced fibrosis by gene profiling and postulated that alteration of the Rho pathway could be associated with radiation induced fibrogenic signals and CTGF sustained expression. <b>Patients and methods:</b> Ileal biopsies from individuals with and without radiation enteritis were analysed by cDNA array, and primary cultures of intestinal smooth muscle cells were established. Then, the effect of pharmacological inhibition of p160 Rho kinase, using Y-27632, was studied by real time reverse transcription-polymerase chain reaction, western blot, and electrophoretic mobility shift assay. <b>Results:</b> Molecular profile analysis of late radiation enteritis showed alterations in expression of genes coding for the Rho proteins. To investigate further the involvement of the Rho pathway in intestinal radiation induced fibrosis, primary intestinal smooth muscle cells were isolated from radiation enteritis. They retained their fibrogenic differentiation in vitro, exhibited a typical cytoskeletal network, a high constitutive CTGF level, increased collagen secretory capacity, and altered expression of genes coding for the Rho family. Rho kinase blockade induced a simultaneous decrease in the number of actin stress fibres, α smooth muscle actin, and heat shock protein 27 levels. It also decreased CTGF levels, probably through nuclear factor κB inhibition, and caused decreased expression of the type I collagen gene. <b>Conclusion:</b> This study is the first showing involvement of the Rho/Rho kinase pathway in radiation fibrosis and intestinal smooth muscle cell fibrogenic differentiation. It suggests that specific inhibition of Rho kinase may be a promising approach for the development of antifibrotic therapies.
Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas
Authors: Howard C. Crawford, Charles R. Scoggins, M. Kay Washington, Lynn M. Matrisian, Steven D. Leach
Journal: Journal of Clinical Investigation (2002)

In gastrointestinal epithelium, metaplastic conversion between predominant cell types is associated with an increased risk of neoplasia. However, the mechanisms regulating metaplastic transitions in adult epithelia are largely undefined. Here we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the majority of human pancreatic ductal adenocarcinoma specimens, but also in human pancreatic intraepithelial neoplasia and metaplastic duct lesions in human and mouse. In a mouse model of pancreatic acinar-to-ductal metaplasia, MMP-7 progressively accumulates during the metaplastic transition, resulting in a concomitant increase in solubilization of Fas ligand (FasL). Under identical conditions, mice either deficient in MMP-7 or carrying an inactive FasL gene are severely inhibited in development of progressive metaplasia and acinar cell apoptosis. Thus, MMP-7 and FasL influence the initiation and maintenance of metaplastic events in pancreatic epithelium, explaining the observed link between metaplasia and apoptosis in pancreas and other gastrointestinal tissues.
In-vitro bronchodilator activity clitoria ternatea and A. precatorius
Authors: Raju Patil, Dnyaneshwar Taur, Ravindra Patil, Dheeraj Ahirwar
Journal: European Respiratory Journal (2013)

Introduction: Asthma is a complex disorder of airway inflammation. The leaves of Abrus precatorius Linn. (Fabacease) and roots of Clitoria ternatea Linn family Fabeaceae have been traditionally used for the treatment of asthma.  Aim and Objectives: Hence, the objective of present study was to evaluate ethanol extract of A. precatorius leaves and C. ternatea root for in-vitro bronchodilator activity using histamine induced contraction of goat tracheal chain.  Method: Trachea chain was suspended in 30 ml organ bath containing Kreb’s solution which was maintained at 37 ± 0.5 oC with continuous aeration. The responses of contraction induced by histamine at concentration (0.5 μg/ml) without test extracts and in the presence of test extracts at a concentration of 2.5-25 μg/ml; in Krebs solution were recorded. The percent relaxation of histamine contracted goat trachea in the presence of test extracts were calculated (Kulshrestha, S. et al. Indian J Pharmacol 1983; 15(2): 107-110).  Results: Result of study reveals that ethanol extract of A. precatorius leaves and C. ternatea root showed the significant relaxations of histamine induced precontracted goat trachea. The percent relaxation of goat trachea 60.22 and 60.80 were observed by ethanol extract of A. precatorius leaves and C. ternatea root at concentration 25 μg/ml respectively as shown in Figure 1.  Conclusions: In conclusion A. precatorius leaves and C. ternatea root shows in-vitro bronchodilator property.