tbuckley/cabot-search huggingface dataset:
Robin Wattie Glashan
Authors: M A Ferro, P H Smith
Journal: BMJ (2004)

Former consultant urologist Huddersfield Royal Infirmary (b Aberdeen 1933; q Aberdeen 1958), died on 13 December 2003.​2003.




Figure 1




Robin was appointed as the first consultant in urological surgery at Huddersfield Royal Infirmary in 1968. He had a refreshingly direct approach in dealing with matters of urological concern and made time to cooperate with those in occupational medicine supervising workers in the chemical and dyeing industries, which led to an excellent service for those at risk from bladder cancer. He was a founder member of the Yorkshire Urological Cancer Research Group, and of the Urological Group of the European Organisation for Research and the Treatment of Cancer. He retired because of poor health in 1990, and returned to Scotland, where he enjoyed salmon fishing. He leaves a wife, Wilma, and three children.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: B. W. J. Mahy, K. E. K. Rowson, C. W. Parr, M. H. Salaman
Journal: The Journal of Experimental Medicine (1965)

Plasma LDH levels were determined in normal and Riley virus-infected mice following treatment with various drugs known to alter the activity of the RES. The rise in plasma LDH level after Riley virus infection was considerably enhanced by previous treatment with thorotrast (to produce blockade of the RES), and decreased by previous treatment with stilboestrol (to stimulate the RES). A dose of 2000 r whole-body x-irradiation, lethal within 3 to 4 days, did not alter the phagocytic activity of the RES, and was without effect on plasma LDH activity in normal mice, or on the rise in plasma LDH level following infection with Riley virus. Blockade of the RES with cholesterol oleate, thorotrast, or zymosan, resulted in a 2- to 3-fold rise in plasma LDH level within a few hours. The level returned to normal by 1 to 3 days. Stimulation of the RES with stilboestrol resulted in a decrease in plasma LDH level by 1 to 2 days in both normal and infected mice, with a return to normal by about a week. Blockade of the RES in uninfected mice with thorotrast or cholesterol oleate, besides increasing the plasma LDH level caused a rise in plasma phosphoglucose isomerase level, but no significant alterations in plasma aldolase or alanine transaminase levels, studied up to 10 days. Riley virus causes a similar pattern of enzyme elevation. It is suggested that the increased levels of certain plasma enzymes in Riley virus-infected mice may be due to competitive inhibition by virus particles of plasma enzyme clearance by the RES.
Trastuzumab Pharmacokinetics Influenced by Extent Human Epidermal Growth Factor Receptor 2–Positive Tumor Load
Authors: Thijs H. Oude Munnink, Eli C. Dijkers, Sabine J. Netters, Marjolijn N. Lub-de Hooge, Adrienne H. Brouwers, Janny G. Haasjes, Carolina P. Schröder, Elisabeth G. de Vries
Journal: Journal of Clinical Oncology (2010)
Resistance Levels of Polyoma Tumors and Tumors of Other Origin to the Cytopathogenic Effect of Polyoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I. Hellström
Journal: JNCI Journal of the National Cancer Institute (1963)

Explants of 10 serially transplanted polyoma tumor lines and of 9 tumor lines of other origin were challenged with a broad spectrum of polyoma virus doses, which included the minimum doses still giving cytopathic changes in normal mouse embryonic cells. The appearance of cytopathic changes was followed after infection, and TCD50 values were determined for the different materials tested. Most polyoma and nonpolyoma tumors were more resistant than embryonic cells to polyoma infection, and there were no systematic differences in virus sensitivity between polyoma tumors and neoplasms of other origin. The resistance was of different degree for different tumors. It also varied among 17 sublines, established from single cells isolated from the same polyoma tumor and propagated in mice. Some of these sublines had the same degree of sensitivity as embryonic cells. The degree of polyoma resistance of these sublines did not appear to be correlated with their ability for spontaneous polyoma release after explantation, as revealed by the plaque and hemagglutination techniques.
Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1 year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure
Authors: U M. Dohn, A Boonen, M L Hetland, M S Hansen, L S Knudsen, A Hansen, O R Madsen, M Hasselquist, J M Moller, M Ostergaard
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> With computed tomography (CT) and radiography, to investigate if repair of bone erosions, defined as regression of erosion scores, occurs during adalimumab treatment of patients with rheumatoid arthritis (RA). <h3>Methods:</h3> Fifty-two patients with RA, naïve to biological agents, with at least two low-grade radiographic erosions in the wrist or metacarpophalangeal (MCP) joints in the same (index) hand, initiated adalimumab 40 mg subcutaneously every other week. Thirty-five patients completed the study (median age 61 years (interquartile range 46–68), disease duration 8 years (3–15)). CT of the index wrist and MCP joints 2–5 and radiographs of hands and forefeet were obtained at baseline, 6 and 12 months. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to Sharp/van der Heijde (radiographs) and OMERACT RA MRI scoring (CT) methods. <h3>Results:</h3> Disease activity score, C-reactive protein, tender and swollen joints count and Health Assessment Questionnaire score had all decreased at 6 and 12 months (wilcoxon signed-ranks test p&lt;0.001). No significant change in any imaging parameters of joint destruction was observed at 6 and 12 months. High intrareader agreements were reached (mean intraobserver intraclass coefficients: 0.96 (CT) and 0.97 (radiography)). The number of patients with change scores exceeding the smallest detectable change (SDC) was comparable on CT and radiography, as were the proportions of patients progressing/regressing. Decreased erosion scores at 12 months were registered in 1.6% and 1.8% of sites assessed on CT and radiography, respectively. <h3>Conclusion:</h3> Repair of erosions in adalimumab-treated patients with RA is rare, but erosive regression, exceeding the SDC, on CT and radiography occurred. The very limited overall erosive progression supports the view that joint destruction is minimal during adalimumab treatment of patients with RA.
Protein Kinase D in the Cardiovascular System
Authors: Metin Avkiran, Alexandra J. Rowland, Friederike Cuello, Robert S. Haworth
Journal: Circulation Research (2008)

The protein kinase D (PKD) family is a recent addition to the calcium/calmodulin-dependent protein kinase group of serine/threonine kinases, within the protein kinase complement of the mammalian genome. Relative to their alphabetically superior cousins in the AGC group of kinases, namely the various isoforms of protein kinase A, protein kinase B/Akt, and protein kinase C, PKD family members have to date received limited attention from cardiovascular investigators. Nevertheless, increasing evidence now points toward important roles for PKD-mediated signaling pathways in the cardiovascular system, particularly in the regulation of myocardial contraction, hypertrophy and remodeling. This review provides a primer on PKD signaling, using information gained from studies in multiple cell types, and discusses recent data that suggest novel functions for PKD-mediated pathways in the heart and the circulation.
The Patient Package Insert-Reply
Authors: Marion J. Finkel
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Richard Dorsey, MD (238:1936, 1977), poses several objections to the concept and utility of patient package inserts (PPIs). The Food and Drug Administration believes that the potential benefits to patients of PPIs—improved compliance with drug regimens, increased patient awareness of the need to avoid certain foods and drugs that may produce potentially hazardous interactions, and improved early recognition and proper interpretation of drug side effects—outweigh the hypothetical risks of providing such information. One of the missions of the FDA is to ensure that prescription drugs are safe, effective, and properly labeled. Whether PPIs are within legal purview of the FDA is before the courts. In any event, legislation pending before Congress (S-1831, HR-8891, S-2040, and S-629) would mandate that the FDA require PPIs. Dr Dorsey cites two consumer surveys that indicate a favorable attitude toward and general desire for written prescription drug information. Yet, he rejects these
Traffic-Related Atmospheric Pollutants Levels during Pregnancy and Offspring’s Term Birth Weight: A Study Relying on a Land-Use Regression Exposure Model
Authors: Rémy Slama, Verena Morgenstern, Josef Cyrys, Anne Zutavern, Olf Herbarth, Heinz-Erich Wichmann, Joachim Heinrich
Journal: Environmental Health Perspectives (2007)

BackgroundSome studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aero-dynamic diameter &lt; 2.5 μm; PM2.5).ObjectiveWe determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight.MethodsWomen from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight &gt; 2,500 g in Munich metropolitan area were included. We assessed PM2.5, PM2.5 absorbance (which depends on the blackness of PM2.5, a marker of traffic-related air pollution), and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight &lt; 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education.ResultsExposure was defined for 1,016 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight &lt; 3,000 g associated with the highest quartile was 1.7 for PM2.5 [95% confidence interval (CI), 1.2–2.7], 1.8 for PM2.5 absorbance (95% CI, 1.1–2.7), and 1.2 for NO2 (95% CI, 0.7–1.7). The PR associated with an increase of 1 μg/m3 in PM2.5 levels was 1.13 (95% CI, 1.00–1.29).ConclusionIncreases in PM2.5 levels and PM2.5 absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight.
The key role of vitamin A in spermatogenesis
Authors: Cathryn A. Hogarth, Michael D. Griswold
Journal: Journal of Clinical Investigation (2010)

Spermatogenesis in adult mammals is highly organized, with the goal being continual sperm production. Vertebrate testes are arranged into recurring cellular associations that vary with time and distance along the tubule. These changes over time and distance are designated the cycle of the seminiferous epithelium and the spermatogenic wave, respectively. In this Review, we briefly outline the roles that follicle-stimulating hormone (FSH) and testosterone play in regulating spermatogenesis and describe our current understanding of how vitamin A regulates germ cell differentiation and how it may lead to the generation of both the cycle of the seminiferous epithelium and the spermatogenic wave.
Resilience is more about being flexible than about staying positive
Authors: Sander L. Koole, Susanne Schwager, Klaus Rothermund
Journal: Behavioral and Brain Sciences (2015)

Abstract Kalisch et al. propose a positive appraisal style as the key mechanism that underlies resilience. The present authors suggest that flexibility in emotion processing is more conducive to resilience than a general positivity bias. People may achieve emotional flexibility through counter-regulation – a dynamic processing bias toward positive stimuli in negative contexts and negative stimuli in positive contexts.
Lecithin: Cholesterol Acyltransferase and Atherosclerosis
Authors: Daniel J. Rader
Journal: Circulation (2009)

P lasma concentrations of high-density lipoprotein choles- terol (HDL-C) are strongly, consistently, and independently inversely associated with risk of atherosclerotic cardiovascular disease (CVD). 1 A series of animal studies in the 1990s, primarily involving overexpression of the major HDL protein apolipoprotein A-I (apoA-I) with subsequent increases in HDL-C, showed reduced progression or even regression of atherosclerosis, fitting nicely with the "HDL hypothesis" that raising HDL-C is causally associated with benefit.However, the last decade has seen several observations that do not follow this simple script.Some examples include the following: (1) the demonstration that scavenger receptor class BI knockout mice have increased HDL-C but increased atherosclerosis 2 ; (2) the suggestion that some persons with high HDL-C levels have "dysfunctional" HDL that may not be protective 3 ; and (3) the observation that the cholesteryl ester transfer protein inhibitor torcetrapib raised HDL-C levels considerably but did not decrease, and indeed increased, cardiovascular risk. 4,5These developments have brought into major question the simple hypothesis that higher HDL-C directly and causally results in reduced atherosclerosis and challenge the approach of developing therapies that raise HDL-C levels.
Outcomes of Patients Presenting With Acute Type A Aortic Dissection in the Setting of Prior Cardiac Surgery
Authors: Nicholas R. Teman, Mark D. Peterson, Mark J. Russo, Marek P. Ehrlich, Truls Myrmel, Gilbert R. Upchurch, Kevin Greason, Mark Fillinger, Alberto Forteza, George Michael Deeb, Daniel G. Montgomery, Kim A. Eagle, Eric M. Isselbacher, Christoph A. Nienaber, Himanshu J. Patel
Journal: Circulation (2013)

Background— Prior cardiac surgery (PCS) can complicate the presentation and management of patients with type A acute aortic dissection (TAAAD). This report from the International Registry of Acute Aortic Dissection examines this hypothesis. Methods and Results— A total of 352 of 2196 patients with TAAAD (16%) enrolled in the International Registry of Acute Aortic Dissection had cardiac surgery before dissection, including coronary artery bypass grafting (34%), aortic or mitral valve surgery (36%), aortic surgery (42%), and other cardiac surgery (16%). Those with PCS were older, had a higher frequency of diabetes mellitus, hypertension, and atherosclerosis, and presented later from symptom onset to hospital presentation and diagnosis (all P &lt;0.05). In-hospital mortality was significantly higher for PCS patients (34% versus 23%; P &lt;0.001). Five-year mortality was independently predicted by PCS (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.05–3.95), age &gt;70 years (HR, 2.65; 95% CI, 1.40–5.05), medical management (HR, 5.10; 95% CI, 2.43–10.71), distal communication (HR, 2.64; 95% CI, 1.35–5.14), and coma (HR, 9.50; 95% CI, 2.05–44.05). Among patients with PCS, in-hospital (43% medical versus 30% surgical; P =0.033) and intermediate-term mortality was higher in patients with medical versus surgical management. Propensity-matched analysis revealed significant increase in mortality with medical management, but not with PCS. Conclusions— PCS delays presentation, diagnosis, and treatment of TAAAD and is an important adverse risk factor for early and intermediate-term mortality. This effect may be because of increased medical management in this patient population.
Enhancement of Antitumor Radiation Efficacy and Consistent Induction of the Abscopal Effect in Mice by ECI301, an Active Variant of Macrophage Inflammatory Protein-1α
Authors: Kenshiro Shiraishi, Yoshiro Ishiwata, Keiichi Nakagawa, Shoji Yokochi, Chiho Taruki, Teruo Akuta, Kuni Ohtomo, Kouji Matsushima, Takuya Tamatani, Shiro Kanegasaki
Journal: Clinical Cancer Research (2008)

We studied whether i.v. administration of a chemokine after local tumor site irradiation could prevent remaining, as well as distant, nonirradiated tumor cell growth by leukocyte recruitment.Tumors were implanted s.c. in the right or both flanks. After local irradiation at the right flank, ECI301, a human macrophage inflammatory protein-1alpha variant was injected i.v. Tumor volumes were measured every 3 days after treatment.In Colon26 adenocarcinoma-bearing BALB/c mice, repeated daily administration (over 3-5 consecutive days) of 2 mug per mouse ECI301 after local irradiation of 6 Gy prolonged survival without significant toxicity, and in about half of the treated mice, the tumor was completely eradicated. Three weekly administrations of ECI301 after local irradiation also led to significant, although less effective, antitumor radiation efficacy. ECI301 also inhibited growth of other syngenic tumor grafts, including MethA fibrosarcoma (BALB/c) and Lewis lung carcinoma (C57BL/6). Importantly, tumor growth at the nonirradiated site was inhibited, indicating that ECI301 potentiated the abscopal effect of radiation. This abscopal effect observed in BALB/c and C57BL/6 mice was tumor-type independent. Leukocyte depletion studies suggest that CD8+ and CD4+ lymphocytes and NK1.1 cells were involved.Marked inhibition of tumor growth at the irradiated site, with complete tumor eradication and consistent induction of the abscopal effect, was potentiated by i.v. administration of ECI301. The results of this study may offer a new concept for cancer therapy, namely chemokine administration after local irradiation, leading to development of novel therapeutics for the treatment of advanced metastatic cancer.
Population depletion activates autonomous CD154-dependent survival in biopsylike Burkitt lymphoma cells
Authors: Anita Challa, Aristides G. Eliopoulos, Michelle J. Holder, Alondra Schweizer Burguete, John D. Pound, Anita Chamba, Gillian Grafton, Richard J. Armitage, Christopher D. Gregory, Hector Martinez-Valdez, Lawrence Young, John Gordon
Journal: Blood (2002)
Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin
Authors: Regis Doyonnas, David B. Kershaw, Christian Duhme, Helen Merkens, Shierley Chelliah, Thomas Graf, Kelly M. McNagny
Journal: The Journal of Experimental Medicine (2001)

Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl−/−) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl−/− mice, they fail to form foot processes and slit diaphragms and instead exhibit cell–cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, podxl−/− mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans.
MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression
Authors: Marilyne Kpetemey, Subhamoy Dasgupta, Smrithi Rajendiran, Susobhan Das, Lee D. Gibbs, Praveenkumar Shetty, Zygmunt Gryczynski, Jamboor K. Vishwanatha
Journal: Molecular Cancer (2015)

Migration and invasion enhancer 1 (MIEN1) is a novel gene found to be abundantly expressed in breast tumor tissues and functions as a critical regulator of tumor cell migration and invasion to promote systemic metastases. Previous studies have identified post-translational modifications by isoprenylation at the C-terminal tail of MIEN1 to favor its translocation to the inner leaflet of plasma membrane and its function as a membrane-bound adapter molecule. However, the exact molecular events at the membrane interface activating the MIEN1-driven tumor cell motility are vaguely understood. MIEN1 was first studied using in-silico analysis on available RNA sequencing data of human breast tissues and its expression was ascertained in breast cells. We performed several assays including co-immunoprecipitation, wound healing, western blotting and immunofluorescence to decipher the molecular events involved in MIEN1-mediated tumor cell migration. Clinically, MIEN1 is predominantly overexpressed in Her-2 and luminal B subtypes of breast tumors, and its increased expression correlates with poor disease free survival. Molecular studies identified a phosphorylation-dependent activation signal in the immunoreceptor tyrosine based activation motif (ITAM) of MIEN1 and the phosphorylation-deficient MIEN1-mutants (Y39F/50 F) to regulate filopodia generation, migration and invasion. We found that ITAM-phosphorylation of MIEN1 is significantly impaired in isoprenylation-deficient MIEN1 mutants indicating that prenylation of MIEN1 and membrane association is required for cross-phosphorylation of tyrosine residues. Furthermore, we identified MIEN1 as a novel interactor of Annexin A2 (AnxA2), a Ca2+ -dependent phospholipid binding protein, which serves as an extracellular proteolytic center regulating plasmin generation. Fluorescence resonance energy transfer (FRET) confirmed that MIEN1 physically interacts with AnxA2 and functional studies revealed that they mutually cooperate to accentuate tumor cell motility. Interestingly, our study identified that ectopic overexpression of MIEN1 significantly enhances Tyr23-phosphorylation on AnxA2, thereby stimulating cell surface translocation of AnxA2 and catalyzing the activation of its proteolytic activity. Our data show that the presence and interaction of both MIEN1 and AnxA2 in breast tumors are crucial drivers of cell motility. Our study has now deciphered a novel regulatory network governing the vicious process of breast tumor cell invasion-metastasis, and findings suggest MIEN1-AnxA2 as prospective targets to counter the deadly disease.
Multiple Cellular Mechanisms Related to Cyclin A1 in Prostate Cancer Invasion and Metastasis
Authors: Barbara Wegiel, Anders Bjartell, Johanna Tuomela, Nishtman Dizeyi, Martina Tinzl, Leszek Helczynski, Elise Nilsson, Leo E. Otterbein, Pirkko Härkönen, Jenny Liao Persson
Journal: JNCI Journal of the National Cancer Institute (2008)

Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized.