tbuckley/cabot-search huggingface dataset:
The Novel Poly(ADP-Ribose) Polymerase Inhibitor, AG14361, Sensitizes Cells to Topoisomerase I Poisons by Increasing the Persistence of DNA Strand Breaks
Authors: Lisa M. Smith, Elaine Willmore, Caroline A. Austin, Nicola J. Curtin
Journal: Clinical Cancer Research (2005)

Poly(ADP-ribose) polymerase (PARP) inhibitors enhance DNA topoisomerase I (topo I) poison-induced cytotoxicity and antitumor activity in vitro and in vivo, but the mechanism has not been defined. We investigated the role of PARP-1 in the response to topo I poisons using PARP-1-/- and PARP-1+/+ mouse embryonic fibroblasts and the potent PARP-1 inhibitor, AG14361 (Ki < 5 nmol/L). PARP-1-/- mouse embryonic fibroblasts were 3-fold more sensitive to topotecan than PARP-1+/+ mouse embryonic fibroblasts (GI50, 21 and 65 nmol/L, respectively). AG14361 caused a >3-fold sensitization of PARP-1+/+ cells to topotecan compared with a <1.4-fold sensitization in PARP-1-/- cells. In human leukemia K562 cells, AG14361 caused a 2-fold sensitization to camptothecin-induced cytotoxicity. AG14361 did not affect the cellular activity of topo I as determined by measurement of cleavable complexes and topo I relaxation activity, showing that sensitization was not due to topo I activation. In contrast, repair of DNA following camptothecin removal, normally very rapid, was significantly retarded by AG14361, resulting in a 62% inhibition of repair 10 minutes after camptothecin removal. This led to a 20% increase in the net accumulation of camptothecin-induced DNA strand break levels in cells coexposed to AG14361 for 16 hours. We investigated the DNA repair mechanism involved using a panel of DNA repair-deficient Chinese hamster ovary cells. AG14361 significantly potentiated camptothecin-mediated cytotoxicity in all cells, except the base excision repair-deficient EM9 cells. Therefore, the most likely mechanism for the potentiation of topo I poison-mediated cytotoxicity by AG14361 is via PARP-1-dependent base excision repair.
F-18 FDG PET Imaging of GVHD-Associated Polymyositis
Authors: Demetrios J. Agriantonis, Scott B. Perlman, Walter L. Longo
Journal: Clinical Nuclear Medicine (2008)

F-18 FDG PET imaging has an established role in the management of lymphoma patients, many of whom receive hematopoietic stem cell transplantation (HSCT). Myositis is a rare manifestation of chronic graft-versus-host disease (GVHD), a common complication of HSCT. We present a case of GVHD-associated polymyositis presenting as intense, diffuse muscle uptake on F-18 FDG PET. The patient is a 35-year-old man with a history of recurrent Hodgkin disease. He presented with low-grade fever, malaise, and diffuse musculoskeletal pain just less than 5 years after HSCT. Chronic GVHD-associated polymyositis is readily treatable with immunosuppressive therapy. Without treatment it can have devastating consequences, notably myoglobin-induced renal failure. Therefore, the interpreting physician should have familiarity with this potential scan finding as suggestive of a treatable complication of HSCT.
774-2 Automated On-Line Assessment of Spatial and Temporal Abnormalities in Regional Left Ventricular Wall Motion Using Color-Encoded Acoustic Quantification of Radiofrequency Echocardiographic Signals: Description of the Method and Early Clinical Application
Authors: Steven Schwartz, Natesa Pandian, Oi-Ling Cao, Mani Vannan, Joanne Zachistal, Janet Simonetti, Marjory Caldeira
Journal: Journal of the American College of Cardiology (1995)
Age-Dependent Impairment of Reendothelialization After Arterial Injury
Authors: Giuseppa Gennaro, Catherine Ménard, Sophie-Élise Michaud, Alain Rivard
Journal: Circulation (2003)

Background— The mechanisms responsible for the association between advanced age and atherosclerotic diseases are not clear. Because atherosclerosis develops in response to local endothelial injuries, we investigated the effect of aging on vascular healing and reendothelialization. Methods and Results— Endothelium denudation was performed by balloon angioplasty of the iliac arteries in young and old New Zealand White rabbits. Planimetric analysis after Evans Blue staining at 28 days after injury showed a significant decrease in reendothelialization in old versus young animals, which was associated with an important increase in neointimal formation in old rabbits. Vascular endothelial growth factor (VEGF) was rapidly induced after balloon injury. However, arterial VEGF expression was significantly reduced in old versus young animals. To confirm the role of VEGF in the age-dependent impairment of reendothelialization, an adenoviral vector encoding for VEGF 165 (adeno-VEGF) was locally delivered at the time of iliac artery angioplasty. Compared with animals treated with the control vector (adeno-βGal), reendothelialization was significantly improved and neointimal formation reduced in old rabbits treated with adeno-VEGF. Conclusions— These results document for the first time an age-dependent impairment of reendothelialization after arterial injury. Our study indicates that VEGF supplementation may represent a useful strategy to accelerate reendothelialization and improve vascular healing in the context of aging.
Clinical Remarks on Affections of the Right Side of the Heart
Authors: T. R. Bradshaw
Journal: BMJ (1894)

JUNE 9, 1| distal side of the righit stumilp-thie best result of the opeiatioin was tile steady diiiiinutioin ol tie ttiiiouii', whitcli continues to the prtcsnt (lay.Convalec-ence was uiex peLtedely r-apid, for tihougli I liad disturbed .>truv-tures wlici hadl rcent ly beci iil a state of acute initlaininiatioin, thiere was iio hiighi temperature.
799 EFFECTS OF RIBAVIRIN ON NK CELL PHENOTYPE AND FUNCTION IN HEPATITIS C VIRUS INFECTION
Authors: A. Markova, B. Bremer, U. Mihm, V. Schlaphoff, K. Stegmann, J. Jaroszewicz, J. Grabowski, S. Lunemann, T. Berg, S. Zeuzem, M.P. Manns, M. Cornberg, H. Wedemeyer
Journal: Journal of Hepatology (2012)
Out-patient Treatment of Ulcerative Colitis
Authors: J. H. Baron, A. M. Connell, T. G. Kanaghinis, J. E. Lennard-Jones, F. A. Jones
Journal: BMJ (1962)

The maintenance of tissue homeostasis in steady state or under stress is dependent on the proper communication between the stem cells and the supporting cells in their microenvironment or "niche". In addition to promoting immune tolerance, regulatory T cells (Tregs) have recently emerged as a critical component of the stem cell niche in the hair follicle (HF), injured muscle, bone marrow, and small intestine to support stem cell differentiation or maintain their quiescence. How Treg cells sense the dynamic signals in the niche environment and communicate with stem cells during tissue regeneration is largely unknown. Here, by using HF as a model, we uncover a hitherto unrecognized function of steroid hormone glucocorticoid that instructs skin-resident Treg cells through glucocorticoid receptor (GR) to facilitate hair follicle stem cell (HFSC) activation and HF regeneration. Ablation of GR signaling in Tregs blocked depilation-induced hair regeneration and natural hair growth without affecting Treg's immune suppressive function. Mechanistic study revealed that GR signaling induces skin-resident Tregs to produce TGF-b3, which directly activates Smad2/3 in HFSCs and facilitates HFSC activation and proliferation. Our study identifies a novel crosstalk between skin-resident Tregs and HFSCs mediated by the GR/TGF-b3 axis, highlighting a new avenue to manipulate Tregs to support tissue regeneration. Supported by NIH R01-AI107027 NIH R01-AI1511123 NIH R21-AI154919 NIH S10-OD023689
Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome
Authors: Michael A White, Jun Kitano, Catherine L Peichel
Journal: Molecular Biology and Evolution (2015)

Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection.
Circadian Variation in te Induction of Intestinal Tumors by N-Methyl-N-nitrosourea in Male C57BL/6N Mice
Authors: F. A. Beland, K. L. Dooley, W. G. Sheldon, R. R. Delongchamp
Journal: JNCI Journal of the National Cancer Institute (1988)

Male C57BL/6N mice were administered a single ip injection of 30 mg of N-methyl-N-nitrosourea (MNU)/kg of body weight. Additional groups were treated similarly every 3 hours for the next 24 hours. Adenocarcinomas of the small intestine were the major treatment-related tumors, with the total incidence being 38% at 250 days after injection. There was a significant circadian variation for tumor induction; the maximum number of intestinal tumors (approximately equal to 55%) tended to occur when the MNU was administered during the middle of the light period (6:00 to 18:00), while the tumor incidence was at a minimum (approximately equal to 10%) when the MNU was given in the middle of the dark phase (18:00 to 6:00). These data are discussed in relation to DNA synthesis and repair and MNU-induced cellular toxicity.
Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation
Authors: Ramon Gomis, Josefa Fernández-Alvarez, Pilar Pizcueta, Mercedes Fernández, Roser Casamitjana, Jaume Bosch, Joan Rodés
Journal: Hepatology (1994)

Increased circulating insulin and glucagon levels are a common observation in patients with cirrhosis, as well as in portal hypertensive models. Hyperinsulinemia and hyperglucagonemia may be caused either by increased beta- and alpha-cell secretion or by defective hepatic clearance of these hormones. To elucidate whether an abnormal endocrine pancreatic function might contribute to the hyperinsulinism or to the hyperglucagonism observed in chronic portal hypertension, insulin and glucagon secretion were measured in vitro in isolated pancreatic islets from rats with partial portal vein ligated and rats with cirrhosis caused by carbon tetrachloride poisoning. Both rats with partial portal vein ligation and rats with cirrhosis caused by carbon tetrachloride poisoning exhibited hyperinsulinism and hyperglucagonism as compared with control rats. Isolated pancreatic islets from both experimental portal hypertensive models showed an impaired insulin secretion after glucose stimulation. On the contrary, glucagon secretion was significantly increased, and there was a markedly enhanced response to arginine. This increased in vitro glucagon production could not be corrected, even in the presence of high glucose concentrations in the incubation medium. Therefore our data show that although hyperglucagonism in rats with partial portal vein ligation and in rats with cirrhosis caused by carbon tetrachloride poisoning is promoted by an enhanced alpha-cell secretion, hyperinsulinism is associated with impaired beta-cell secretion.
F-18 FDG PET/CT Imaging in a Case of Primary Choriocarcinoma in the Retroperitoneum
Authors: Sébastien Cimarelli, Emmanuel Deshayes, Thomas Mognetti, Pierre Biron, Claude Desuzinges, Michel Rivoire, Francesco Giammarile
Journal: Clinical Nuclear Medicine (2009)

Nonseminomatous germ cell tumors (GCTs) represent 60% of all GCTs, the most common malignancy in young men. Extragonadal primary GCTs are a rare entity and their origin remains unclear. F-18 fluorodeoxyglucose positron emission tomography (PET) is a promising imaging tool for GCT staging and treatment evaluation. We report the case of a 23-year-old man presenting with retroperitoneal primary choriocarcinoma associated with pulmonary and hepatic metastases. In addition to conventional imaging techniques, the F-18 fluorodeoxyglucose PET evaluation at staging and after chemotherapy improved the management of this patient. Particularly, PET findings before surgery were correlated with histologic results.
EU commissioner says pandemic likely, but may not be deadly
Authors: R. Watson
Journal: BMJ (2009)

European Union governments will increase cooperation among themselves in the fight against the novel flu virus but have not committed themselves to sharing their stockpiles of vaccines and antiflu drugs.

Health ministers from the 27 EU countries also rejected calls from France to introduce a collective travel ban on flights to Mexico when they held an emergency meeting in Luxembourg on 30 April.

The cooperation will involve use of a common definition to identify infections, cooperation with drug companies …
Legal barriers might have catastrophic effects
Authors: P. Browett, S. Palmer
Journal: BMJ (1996)

Linda Delany has addressed the question of volunteering children for bone marrow transplant donation purely within a legal framework. She suggests that two legal approaches are possible: one which centres on treatment which is in “the best interests of the child” and the other which looks at treatment which is “not against the interests of the child.”

Despite these two contrasting legal approaches, she subsequently considers only the first: the principle that the procedure should be performed only if it serves the best interest of the donor child. She argues that children need to be protected by an independent authority from being “volunteered” for bone marrow donation. The second approach, however, is equally relevant: that parents can give …
Physician Assignment Policies of the US Army
Authors: Bedford H. Berrey
Journal: JAMA (1966)

Will I be used in my specialty? I don't care where I go, just let me work in my specialty.  Such questions and statements are repeated daily in interviews with physicians about to enter active duty under the aegis of Selective Service (and to a lesser extent from Berry Plan participants). The consistent regularity of these comments indicates that a paucity of information exists concerning physician classification and assignment procedures of the Surgeon General, Department of the Army.  The purpose of this communication is to identify the procedures used by the Medical Corps Branch, Office of the Surgeon General, to assure the most effective utilization of the newly commissioned physician. It is not the purpose to discuss selective service methods, commissioning procedures or other administrative techniques used in bringing the qualified physician to active duty. Our attention, therefore, is directed solely to the initial assignment procedure which cannot begin until the individual's preference questionnaire is received in the
Aspiration biopsy of carcinoma of the pancreas.
Authors: B A Shorey
Journal: Gut (1975)

Peroperative pancreatic aspiration biopsies were performed on 21 patients with pancreatic lesions using a standard 20-ml disposable syringe and a 21-gauge needle. No complications were recorded which could be attributed to this procedure. A further 10 aspiration biopsies were carried out on postmortem specimens in an attempt to determine the accuracy of this method in the diagnosis of carcinoma of the pancreas. It is concluded that peroperative pancreatic needle biopsy is a safe procedure which is easily performed without special instruments. In can be of enormous value to the surgeon in planning the treatment of patients with pancreatic lesions. In cases where there is an operable mass in the pancreas it offers a simple and quick method of determining the presence of malignant cells and thus definitive surgery may be performed with confidence. For the inoperable cases it offers a method of histological confirmation of the operative findings.
Adenosine triphosphate-dependent taurocholate transport in human liver plasma membranes.
Authors: H Wolters, F Kuipers, M J Slooff, R J Vonk
Journal: Journal of Clinical Investigation (1992)

Transport systems involved in uptake and biliary secretion of bile salts have been extensively studied in rat liver; however, little is known about these systems in the human liver. In this study, we investigated taurocholate (TC) transport in canalicular and basolateral plasma membrane vesicles isolated from 15 human livers (donor age 6-64 yr). ATP stimulated the uptake of TC into both canalicular and basolateral human liver plasma membrane vesicles (cLPM and blLPM, respectively). Considerable interindividual variations in the transport velocity were observed in the different membrane preparations used: 9.0 +/- 1.3 (mean +/- SEM, n = 17; range 1.6-18.0) and 9.3 +/- 2.0 (range 1.1-29.8) pmol TC.mg protein-1.min-1 at 1.0 microM TC for cLPM and blLPM, respectively. TC transport was temperature sensitive and showed saturation kinetics with a high affinity for TC (Km 4.2 +/- 0.7 microM and 3.7 +/- 0.5 microM for cLPM and blLPM, respectively). Transport was dependent on the ATP concentration and saturable (Km 0.25 +/- 0.03 mM, n = 3). Neither nitrate, which reduces membrane potential, nor the protonophore FCCP strongly inhibited ATP-dependent TC transport, indicating that membrane potential and proton gradient are not involved in this process. TC transport was significantly inhibited by the classical anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (250 microM) and the glutathione conjugate S-(2,4-dinitrophenyl)glutathione (100 microM). In conclusion, high affinity ATP-dependent TC transport is present in human liver at both the canalicular and the basolateral sides of the hepatocyte.
IMMEDIATE AND EARLY EFFECTS OF ALCOHOL SEPTAL ABLATION ON THE RIGHT HEART AND LEFT ATRIUM
Authors: Beevash Ray, Justine Lachmann, Jerald L. Cohen, George Gubernikoff, Joshua R. DeLeon, Juan Gaztanaga, Nickolaos Michelakis, Srihari S. Naidu
Journal: Journal of the American College of Cardiology (2012)
Aggression and violent behaviour in general practice: population based survey in the north of England
Authors: G. J Ness
Journal: BMJ (2000)

explicit judgments of risk.Clinicians should not assume that their patients and professional colleagues are likely to share their opinion whether treatment for hypertension is worth while.I thank all the people who took part in this study, Brian Tom from the Centre for Applied Medical Statistics at Cambridge University for statistical advice, and Peter Brambleby and Malcolm Adams for their constructive comments.NS is the sole author and acts
Veterans’ Affairs and PTSD
Authors: Mike Mitka
Journal: JAMA (2011)

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Vessel maturation schedule determines vulnerability to neuronal injuries of prematurity
Authors: Tamar Licht, Talia Dor-Wollman, Ayal Ben-Zvi, Gadiel Rothe, Eli Keshet
Journal: Journal of Clinical Investigation (2015)

Premature birth is a major risk factor for multiple brain pathologies, notably periventricular leukomalacia (PVL), which is distinguished by bilateral necrosis of neural tissue around the ventricles and a sequela of neurological disturbances. The 2 hallmarks of brain pathologies of prematurity are a restricted gestational window of vulnerability and confinement of injury to a specific cerebral region. Here, we examined the proposition that both of these features are determined by the state of blood vessel immaturity. We developed a murine genetic model that allows for inducible and reversible VEGF blockade during brain development. Using this system, we determined that cerebral vessels mature in a centrifugal, wave-like fashion that results in sequential acquisition of a functional blood-brain barrier and exit from a VEGF-dependent phase, with periventricular vessels being the last to mature. This developmental program permitted selective ablation of periventricular vessels via episodic VEGF blockade within a specific, vulnerable gestational window. Enforced collapse of ganglionic eminence vessels and resultant periventricular neural apoptosis resulted in a PVL-like phenotype that recapitulates the primary periventricular lesion, ventricular enlargement, and the secondary cortical deficit in out-migrating GABAergic inhibitory interneurons. These findings provide an animal model that reproduces the temporal and spatial specificities of PVL and indicate that damage to VEGF-dependent, immature periventricular vessels contributes to PVL development.
NHS Wales should make patients "customer owners" of their care, report says
Authors: N. Hawkes
Journal: BMJ (2014)

Healthcare services in Wales may be able to learn from the native people of Alaska, a new report has claimed.1 

The Nuka system, named after the Alaska Native word for strength, abolished the word “patient,” rejected the alternative term “service user,” and instead calls the public it serves “customer owners” to emphasise that they are in charge of their own healthcare.

The entire system was redesigned to promise same day consultations for people who call in …
Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immunoglobulin concentrations
Authors: Ricardo U. Sorensen, Lily E. Leiva, Felipe C. Javier, Daniela M. Sacerdote, Nicola Bradford, Boyd Butler, Patricia A. Giangrosso, Cleveland Moore
Journal: Journal of Allergy and Clinical Immunology (1998)