tbuckley/cabot-search huggingface dataset:
Carcinoma of the Stomach: a 10-year Survey of Results and of Factors Affecting Prognosis
Authors: V. S. Brookes, J. A. H. Waterhouse, D. J. Powell
Journal: BMJ (1965)

Birmingham Hospitals.It is based on statistics submitted to the Birmingham Regional Cancer Registry by the United Birmingham Hospitals and hospitals of the Birmingham Regional Hospital Board.We would like to express our thanks to all the members of the staffs of those hospitals who have made information available to the Registry.
The Last Refreshing Taste
Authors: Paul Rousseau
Journal: JAMA (1997)

<h3>To the Editor.</h3> —As Dr Bone continues his confrontation with mortality and metastatic renal cancer, his touching and eloquent writings<sup>1,2</sup>incite us to provide compassionate and irreproachable care to severely ill and dying patients. Unfortunately, care of terminally ill people is a neglected aspect of medical care,<sup>1</sup>despite the fact that most physicians come in close proximity to death during daily encounters with patients. To compound the neglect, the locale of the deathbed scene has migrated from a homebound environment to an institutional setting, with death frequently occurring alone and without family, friends,<sup>3</sup>or physician in attendance, particularly in long-term care facilities. Regrettably, absence or withdrawal of a physician from terminal care negatively alters the physician-patient relationship during its final and vulnerable phase, and fosters familial discontent and an image of patient abandonment. However, such detachment may reflect a universal fear of death and an identification with
Brevetoxin Forms Covalent DNA Adducts in Rat Lung Following Intratracheal Exposure
Authors: Faisal F.Y. Radwan, John S. Ramsdell
Journal: Environmental Health Perspectives (2008)

BackgroundHuman exposure to brevetoxins produced by the red tide organism, Karenia brevis, is an increasing public health concern. Using in vitro exposure of rat liver cells to brevetoxin B (PbTx-2), the primary toxin product of K. brevis, we previously showed that it formed C27,28-epoxy brevetoxin metabolites capable of covalently binding to nucleic acids, a common initiation step for carcinogenesis.ObjectiveThis study was undertaken to evaluate nucleic acid adduction in lung following in vitro and in vivo brevetoxin exposures.MethodsTo clarify reactions of brevetoxin epoxide with DNA, we analyzed reaction products of PbTx-6 (a C27,28 epoxide metabolite of brevetoxin B) with nucleosides. We also analyzed adducts from nucleic acid hydrolysates of isolated rat lung cells treated with PbTx-2 or PbTx-6 in vitro and lung tissue from rats after intratracheal exposure to PbTx-2 or PbTx-6 at 45 μg toxin/kg body weight.ResultsOur results indicate that PbTx-2 forms DNA adducts with cytidine after treatment of isolated lung cells, and forms DNA adducts with adenosine and guanosine after intratracheal exposure.ConclusionsThese results are consistent with metabolic activation of highly reactive brevetoxin intermediates that bind to nucleic acid. These findings provide a basis for monitoring exposure and assessing the hazard associated with depurination of brevetoxin–nucleotide adducts in lung tissue.
System for handling complaints against the English NHS fails on all counts
Authors: C. Dyer
Journal: BMJ (2008)

The system for handling complaints against the NHS in England fails on all the measures of a good complaints system, says a report from the United Kingdom’s public spending watchdog, the National Audit Office (NAO). It is not accessible or responsive, and lessons are not being learnt to prevent mistakes in future.

About one in seven people who used the NHS or social care services in the past three years were dissatisfied with their experiences, according to a survey by the office. But of those unhappy with their NHS care, only 5% went on to make a formal complaint.

Karen Taylor, head of health studies at the audit office, said, “The …
Degradation of endogenous bacterial cell wall polymers by the muralytic enzyme mutanolysin prevents hepatobiliary injury in genetically susceptible rats with experimental intestinal bacterial overgrowth.
Authors: S N Lichtman, E E Okoruwa, J Keku, J H Schwab, R B Sartor
Journal: Journal of Clinical Investigation (1992)

Jejunal self-filling blind loops with subsequent small bowel bacterial overgrowth (SBBO) induce hepatobiliary injury in genetically susceptible Lewis rats. Lesions consist of portal tract inflammation, bile duct proliferation, and destruction. To determine the pathogenesis of SBBO-induced hepatobiliary injury, we treated Lewis rats with SBBO by using several agents with different mechanisms of activity. Buffer treatment, ursodeoxycholic acid, prednisone, methotrexate, and cyclosporin A failed to prevent SBBO-induced injury as demonstrated by increased plasma aspartate aminotransferase (AST) and elevated histology scores. However, hepatic injury was prevented by mutanolysin, a muralytic enzyme whose only known activity is to split the beta 1-4 N-acetylmuramyl-N-acetylglucosamine linkage of peptidoglycan-polysaccharide (PG-PS), a bacterial cell wall polymer with potent inflammatory and immunoregulatory properties. Mutanolysin therapy started on the day blind loops were surgically created and continued for 8 wk significantly diminished AST (101 +/- 37 U/liter) and liver histology scores (2.2 +/- 2.7) compared to buffer-treated rats (228 +/- 146 U/liter, P < 0.05, 8.2 +/- 1.9, P < 0.001 respectively). Mutanolysin treatment started during the early phase of hepatic injury, 16-21 d after surgery, decreased AST in 7 of 11 rats from 142 +/- 80 to 103 +/- 24 U/liter contrasted to increased AST in 9 of 11 buffer-treated rats from 108 +/- 52 to 247 +/- 142 U/liter, P < 0.05. Mutanolysin did not change total bacterial numbers within the loop, eliminate Bacteroides sp., have in vitro antibiotic effects, or diminish mucosal PG-PS transport. However, mutanolysin treatment prevented elevation of plasma anti-PG antibodies and tumor necrosis factor-alpha (TNF alpha) levels which occurred in buffer treated rats with SBBO and decreased TNF alpha production in isolated Kupffer cells stimulated in vitro with PG-PS. Based on the preventive and therapeutic activity of this highly specific muralytic enzyme, we conclude that systemic uptake of PG-PS derived from endogenous enteric bacteria contributes to hepatobiliary injury induced by SBBO in susceptible rat strains.
Color Doppler Flows of Corkscrew Collaterals in Thromboangiitis Obliterans (Buerger's Disease) Using Color Duplex Ultrasonography
Authors: Yuichi Fujii, Junko Soga, Takayuki Hidaka, Takaki Hata, Naomi Idei, Noritaka Fujimura, Shinsuke Mikami, Tatsuya Maruhashi, Yasuki Kihara, Kensuke Noma, Yukihito Higashi
Journal: Journal of the American College of Cardiology (2011)
Intragraft localization of activated nuclear factorκB in recurrent hepatitis C virus disease following liver transplantation
Authors: Anderson S. Gaweco, Russell H. Wiesner, Michael Porayko, Vinod K. Rustgi, Sherri Yong, Raza Hamdani, James Harig, Gregorio Chejfec, Kenneth D. McClatchey, David H. Van Thiel
Journal: Hepatology (2000)

Nuclear factor kappaB (NF-kappaB) is activated during viral infection and is central to the regulation of host immune responses. The NF-kappaB activation status and its morphological sources were assessed by immunohistochemistry in allograft biopsy specimens of orthotopic liver transplantation patients with recurrent hepatitis C virus (HCV). Hepatocellular NF-kappaB immunostaining was detected in HCV cases compared with controls (nontransplant: P <.001; transplant: P =.006), which correlated with the number of NF-kappaB positive hepatocytes (P =.007) and contrasted to the absent to weak staining of controls (nontransplant: P =.001; transplant: P =.009). Enhanced NF-kappaB staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-kappaB immunoreactivity was detected in CD68-positive Kupffer cells and macrophages of all HCV specimens compared with a few controls (nontransplant: P <.001; transplant: P =.001) and contrasted to the weak staining of controls (nontransplant: P <.001; transplant: P =.001). NF-kappaB-positive immunoreactivity correlated with the number of T cell receptor (TCR) alpha/beta-positive lymphocytes (P <.001), which was not observed in controls. In those HCV cases showing evidence of necroinflammatory activity (grade) and individual features of portal inflammation, periportal inflammation/piecemeal necrosis, lobular inflammation, and fibrosis (stage), higher NF-kappaB staining intensity scores within bile ducts, proliferating ductules, hepatocytes (piecemeal necrosis: P =.016; stage: P =.030), and lymphocytes (stage: P =.044) and increased number of NF-kappaB-positive cells within bile ducts, proliferating ductules (grade, lobular inflammation, piecemeal necrosis, stage: P =.022), hepatocytes, and lymphocytes were observed. Increased staining intensity and frequency of NF-kappaB-positive cells were similarly observed in HCV-positive allografts obtained from patients under tacrolimus- compared with cyclosporine-based immunosuppression. These data implicate an immunoregulatory role of intragraft NF-kappaB activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.
Radiofrequency ablation for early esophageal squamous cell neoplasia
Authors: Y. Zhang, J. Bergman, B. Weusten, S. Dawsey, D. Fleischer, N. Lu, S. He, G. Wang
Journal: Endoscopy (2010)

Esophageal cancer is the sixth most common cause of cancer death in the world [1]. Over 80 % of esophageal cancers occur in developing countries [1], and in these areas, 90 % of these cancers are esophageal squamous cell carcinoma (ESCC) [2]. The precursor lesion of ESCC is squamous intraepithelial neoplasia (squamous dysplasia), defined histologically as nuclear atypia (enlargement, pleomorphism, and hyperchromasia), loss of normal cellular polarity, and abnormal tissue maturation [3] [4]. The World Health Organization (WHO) subclassifies squamous intraepithelial neoplasia into low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN), depending on the extent of the nuclear atypia and the involvement of the epithelium [4]. In China, where ESCC and its precursors are very common in some areas, a three-tier system is used, including LGIN (mild dysplasia, involving the lower third of the epithelium), medium-grade intraepithelial neoplasia (MGIN, moderate dysplasia, involving the lower two-thirds of the epithelium), and HGIN (severe dysplasia, involving the full thickness of the epithelium) [3]. Follow-up studies in China have shown that the rate of progression to ESCC differs significantly between LGIN (5.3 % over 3.5 years), MGIN (26.7 %), and HGIN (65.2 %), and because of their significant risk of progression, MGIN and HGIN are targets for screening and therapy [5] [6].
Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation
Authors: Aleksandra Isakovic, Zoran Markovic, Nadezda Nikolic, Biljana Todorovic-Markovic, Sanja Vranjes-Djuric, Ljubica Harhaji, Nevena Raicevic, Nebojsa Romcevic, Dana Vasiljevic-Radovic, Miroslav Dramicanin, Vladimir Trajkovic
Journal: Biomaterials (2006)
Excessive Urinary 5-Hydroxy-3-Indole Acetic Acid in the Absence of a Metastatic Carcinoid
Authors: FABER F. MCMULLEN, HUGH H. HANSON
Journal: Circulation (1958)

Considerable interest has been aroused in the dianosis of the malignant carcinoid syndrome and the diagnostic reliability of increased urinary excretion of 5-hydroxy-3-indole acetic acid. The authors present observations important to this problem.
Third-Generation β-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux
Authors: Leszek Kalinowski, Lawrence W. Dobrucki, Miroslawa Szczepanska-Konkel, Maciej Jankowski, Ludmila Martyniec, Stefan Angielski, Tadeusz Malinski
Journal: Circulation (2003)

Nebivolol and carvedilol are third-generation beta-adrenoreceptor antagonists, which unlike classic beta-blockers, have additional endothelium-dependent vasodilating properties specifically related to microcirculation by a molecular mechanism that still remains unclear. We hypothesized that nebivolol and carvedilol stimulate NO release from microvascular endothelial cells by extracellular ATP, which is a well-established potent autocrine and paracrine signaling factor modulating a variety of cellular functions through the activation of P2-purinoceptors. Contraction and relaxation of renal glomerular vasculature were measured by determination of intracapillary volume with [3H]-inulin. Biologically active NO was measured with highly sensitive porphyrinic NO microsensors in a single glomerular endothelial cell (GEC). Extracellular ATP was measured by a luciferin-luciferase assay. Enzymatic degradation of extracellular ATP by apyrase and blockade of P2Y-purinoceptors by suramin or reactive blue 2 inhibited both beta-blocker-induced glomerular vasorelaxations and beta-blocker-stimulated NO release from GECs. Both beta-blocker-induced vasorelaxations were in the micromolar concentration range identical to that required for the beta-blocker stimulation of ATP and NO release from GECs. The maximum of NO release for nebivolol and carvedilol was very similar (188+/-14 and 226+/-17, respectively). Blockade of ATP release by a mechanosensitive ion channel blocker, Gd3+, inhibited the beta-blocker-dependent release of ATP and NO from GECs. These results demonstrate for the first time that nebivolol and carvedilol induce relaxation of renal glomerular microvasculature through ATP efflux with consequent stimulation of P2Y-purinoceptor-mediated NO release from GECs.
Environmental lead and children's intelligence: a systematic review of the epidemiological evidence
Authors: S J Pocock, M Smith, P Baghurst
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To quantify the magnitude of the relation between full scale IQ in children aged 5 or more and their body burden of lead. <b>Design</b>: A systematic review of 26 epidemiological studies since 1979: prospective studies of birth cohorts, cross sectional studies of blood lead, and cross sectional studies of tooth lead. <b>Setting</b>: General populations of children &gt;=5 years. Main outcome measures - For each study, the regression coefficient of IQ on lead, after adjustment for confounders when possible, was used to derive the estimated change in IQ for a specific doubling of either blood or tooth lead. <b>Results</b>: The five prospective studies with over 1100 children showed no association of cord blood lead or antenatal maternal blood lead with subsequent IQ. Blood lead at around age 2 had a small and significant inverse association with IQ, somewhat greater than that for mean blood lead over the preschool years. The 14 cross sectional studies of blood lead with 3499 children showed a significant inverse association overall, but showed more variation in their results and their ability to allow for confounders. The seven cross sectional studies of tooth lead with 2095 children were more consistent in finding an inverse association, although the estimated magnitude was somewhat smaller. Overall synthesis of this evidence, including a meta-analysis, indicates that a typical doubling of body lead burden (from 10 to 20 μg/dl (0.48 to 0.97 μmol/l) blood lead or from 5 to 10 μg/g tooth lead) is associated with a mean deficit in full scale IQ of around 1-2 IQ points. <b>Conclusion</b>: While low level lead exposure may cause a small IQ deficit, other explanations need considering: are the published studies representative; is there inadequate allowance for confounders; are there selection biases in recruiting and following children; and do children of lower IQ adopt behaviour which makes them more prone to lead uptake (reverse causality)? Even if moderate increases in body lead burden adversely affect IQ, a threshold below which there is negligible influence cannot currently be determined. Because of these uncertainties, the degree of public health priority that should be devoted to detecting and reducing moderate increases in children9s blood lead, compared with other important social detriments that impede children9s development, needs careful consideration.
Phenolic and Tyrosyl Ring Deiodination of Iodothyronines in Rat Brain Homogenates
Authors: Michael M. Kaplan, Kimberlee A. Yaskoski
Journal: Journal of Clinical Investigation (1980)

Conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) in rat brain has recently been shown in in vivo studies. This process contributes a substantial fraction of endogenous nuclear T3 in the rat cerebral cortex and cerebellum. Production of T4 metabolites besides T3 in the brain has also been suggested. To determine the nature of these reactions, we studied metabolism of 0.2-1.0 nM [125I]T4 and 0.1-0.3 nM [131I]T3 in whole homogenates and subcellular fractions of rat cerebral cortex and cerebellum. Dithiothreitol (DTT) was required for detectable metabolic reactions: 100 mM DTT was routinely used. Ethanol extracts of incubation mixtures were analyzed by paper chromatography in t-amyl alcohol:hexane:ammonia and in 1-butanol:acetic acid. Rates of production of iodothyronines from T4 and T3 were greater at pH 7.5 than at 6.4 or 8.6 and greater at 37°C than at 22° or 4°C. Lowering the pH, reducing the protein or DTT concentrations, and preheating homogenates to 100°C all increased excess I− production but reduced iodothyronine production.
Inflammation caused by intracutaneous implantation of stratum corneum
Authors: R. MARKS, K. DALZIEL, P. J. DYKES
Journal: British Journal of Dermatology (1984)

When an epidermoid cyst ruptures, a granulomatous infiltrate develops around the damaged structure. The same is true when other horn-containing cysts release their content into the epidermis. A similar type of inflammation may be observed in the dermis around disrupted and horn-filled follicles in acne vulgaris. In this paper we describe experiments in which a granulomatous inflammation has been produced in guinea-pig skin by the intracutaneous implantation of stratum corneum and discuss the potential of this system as a model for the inflammation in acne.
Alcohol intake and iron overload: Another role for hepcidin?
Authors: Kris V. Kowdley
Journal: Hepatology (2007)

Patients with alcoholic liver disease frequently exhibit iron overload in association with increased hepatic fibrosis. Even moderate alcohol consumption elevates body iron stores; however, the underlying molecular mechanisms are unknown. Hepcidin, a circulatory peptide synthesized in the liver, is a key mediator of iron metabolism. Ethanol metabolism significantly down-regulated both in vitro and in vivo hepcidin mRNA and protein expression. 4-Methylpyrazole, a specific inhibitor of the alcohol-metabolizing enzymes, abolished the effects of ethanol on hepcidin. However, ethanol did not alter the expression of transferrin receptor1 and ferritin or the activation of iron regulatory RNA-binding proteins, IRP1 and IRP2. Mice maintained on 10-20% ethanol for 7 days displayed down-regulation of liver hepcidin expression without changes in liver triglycerides or histology. This was accompanied by elevated duodenal divalent metal transporter1 and ferroportin protein expression. Injection of hepcidin peptide negated the effect of ethanol on duodenal iron transporters. Ethanol down-regulated hepcidin promoter activity and the DNA binding activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha) but not beta. Interestingly, the antioxidants vitamin E and N-acetylcysteine abolished both the alcohol-mediated down-regulation of C/EBPalpha binding activity and hepcidin expression in the liver and the up-regulation of duodenal divalent metal transporter 1. Collectively, these findings indicate that alcohol metabolism-mediated oxidative stress regulates hepcidin transcription via C/EBPalpha, which in turn leads to increased duodenal iron transport.
Comparison of Surgery and Prolonged Spironolactone Therapy in Patients with Hypertension, Aldosterone Excess, and Low Plasma Renin
Authors: J. J. Brown, D. L. Davies, J. B. Ferriss, R. Fraser, E. Haywood, A. F. Lever, J. I. S. Robertson
Journal: BMJ (1972)

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery. Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment. In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied. Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped. In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.
Phosphate Analogs Block Adaptation in Hair Cells by Inhibiting Adaptation-Motor Force Production
Authors: Ebenezer N. Yamoah, Peter G. Gillespie
Journal: Neuron (1996)

<h2>Abstract</h2> To ensure optimal sensitivity for mechanoelectrical transduction, hair cells adapt to prolonged stimuli using active motors. Adaptation motors are thought to employ myosin molecules as their force-producing components. We find that beryllium fluoride, vanadate, and sulfate, phosphate analogs that inhibit the ATPase activity of myosin, inhibit adaptation by abolishing motor force production. Phosphate analogs interact with a 120-kDa bundle protein, most likely myosin Iβ, in a manner that coincides with their effects on adaptation. Features of transduction following inhibition of motor force production suggest that the gating and extent springs of the hair cell orient in parallel at rest and that the negative limit of adaptation arises when force in the stretched extent spring matches the force output of the adaptation motor.
Is cultivating “biological blindness” a viable route to understanding behavioral phenomena?
Authors: Andreas Olsson, Ame Öhman
Journal: Behavioral and Brain Sciences (2009)

Abstract Mitchell et al. propose that associative learning in humans and other animals requires the formation of propositions by means of conscious and controlled reasoning. This approach neglects important aspects of current thinking in evolutionary biology and neuroscience that support the claim that learning, here exemplified by fear learning, neither needs to be conscious nor controlled.
B-cell linear epitopes mapping of antigen-5 allergen from Polybia paulista wasp venom
Authors: José Roberto Aparecido dos Santos-Pinto, Lucilene Delazari dos Santos, Helen Andrade Arcuri, Anally Ribeiro da Silva Menegasso, Paloma Napoleão Pêgo, Keity Souza Santos, Fábio Morato Castro, Jorge Elias Kalil, Salvatore Giovanni De-Simone, Mario Sergio Palma
Journal: Journal of Allergy and Clinical Immunology (2014)