tbuckley/cabot-search huggingface dataset:
Adenosine triphosphate-dependent copper transport in isolated rat liver plasma membranes.
Authors: M Dijkstra, G In 't Veld, G J van den Berg, M Müller, F Kuipers, R J Vonk
Journal: Journal of Clinical Investigation (1995)

The process of hepatobiliary copper (Cu) secretion is still poorly understood: Cu secretion as a complex with glutathione and transport via a lysosomal pathway have been proposed. The recent cloning and sequencing of the gene for Wilson disease indicates that Cu transport in liver cells may be mediated by a Cu transporting P-type ATPase. Biochemical evidence for ATP-dependent Cu transport in mammalian systems, however, has not been reported so far. We have investigated Cu transport in rat liver plasma membrane vesicles enriched in canalicular or basolateral membranes in the presence and absence of ATP (4 mM) and an ATP-regenerating system. The presence of ATP clearly stimulated uptake of radiolabeled Cu (64Cu, 10 microM) into canalicular plasma membrane vesicles and, to a lesser extent, also into basolateral plasma membrane vesicles. ATP-dependent Cu transport was dose-dependently inhibited by the P-type ATPase inhibitor vanadate, and showed saturation kinetics with an estimated Km of 8.6 microM and a Vmax of 6.9 nmol/min/mg protein. ATP-stimulated Cu uptake was similar in canalicular membrane vesicles of normal Wistar rats and those of mutant GY rats, expressing a congenital defect in the activity of the ATP-dependent canalicular glutathione-conjugate transporter (cMOAT). These studies demonstrate the presence of an ATP-dependent Cu transporting system in isolated plasma membrane fractions of rat liver distinct from cMOAT.
Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs
Authors: Martin Siegemund, Jasper van Bommel, Lothar A. Schwarte, Wolfgang Studer, Thierry Girard, Stephan Marsch, Peter Radermacher, Can Ince
Journal: Intensive Care Medicine (2005)
Increased urinary leukotriene E4 excretion in obstructive sleep apnea: Effects of obesity and hypoxia
Authors: Françoise Stanke-Labesque, Magnus Bäck, Blandine Lefebvre, Renaud Tamisier, Jean-Philippe Baguet, Nathalie Arnol, Patrick Lévy, Jean-Louis Pépin
Journal: Journal of Allergy and Clinical Immunology (2009)
Non-Fatal Case of Curling's Ulcer in a Child
Authors: A. Blundell
Journal: BMJ (1954)

Hippocampal place cells show position-specific activity thought to reflect a self-localization signal. Several reports also point to some form of goal encoding by place cells. We investigated this by asking whether they also encode the value of spatial goals, which is crucial information for optimizing goal-directed navigation. We used a continuous place navigation task in which male rats navigate to one of two (freely chosen) unmarked locations and wait, triggering the release of reward, which is then located and consumed elsewhere. This allows sampling of place fields and dissociates spatial goal from reward consumption. The two goals varied in the amount of reward provided, allowing assessment of whether the rats factored goal value into their navigational choice and of possible neural correlates of this value. Rats successfully learned the task, indicating goal localization, and they preferred higher-value goals, indicating processing of goal value. Replicating previous findings, there was goal-related activity in the out-of-field firing of CA1 place cells, with a ramping-up of firing rate during the waiting period, but no general overrepresentation of goals by place fields, an observation that we extended to CA3 place cells. Importantly, place cells were not modulated by goal value. This suggests that dorsal hippocampal place cells encode space independently of its associated value despite the effect of that value on spatial behavior. Our findings are consistent with a model of place cells in which they provide a spontaneously constructed value-free spatial representation rather than encoding other navigationally relevant but nonspatial information. <b>SIGNIFICANCE STATEMENT</b> We investigated whether hippocampal place cells, which compute a self-localization signal, also encode the relative value of places, which is essential information for optimal navigation. When choosing between two spatial goals of different value, rats preferred the higher-value goal. We saw out-of-field goal firing in place cells, replicating previous observations that the cells are influenced by the goal, but their activity was not modulated by the value of these goals. Our results suggest that place cells do not encode all of the navigationally relevant aspects of a place, but instead form a value-free “map” that links to such aspects in other parts of the brain.
Inhibition of PDGF, TGF-β, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib
Authors: Yuqing Liu, Zhuo Wang, Shu Qin Kwong, Eric Lik Hang Lui, Scott L. Friedman, Fu Rong Li, Reni Wing Chi Lam, Guo Chao Zhang, Hui Zhang, Tao Ye
Journal: Journal of Hepatology (2011)
Identifying Rare Events in Rare Diseases
Authors: Edward F. Attiyeh, John M. Maris
Journal: Clinical Cancer Research (2014)

Utilizing genomic signatures from diagnostic tumor samples to forecast clinical behavior and response to therapy has long been a goal, and we are now poised to further refine how we can identify the relatively rare patients with aggressive neuroblastoma masquerading as patients with a more benign form of the disease. Clin Cancer Res; 21(8); 1782-5. ©2014 AACR. See related article by Oberthuer et al., p. 1904.
Small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis
Authors: Jing Zhang, Xiangliang Ren, Wei Shi, Sihan Wang, Haixu Chen, Bowen Zhang, Zhidong Wang, Yong Zhou, Lin Chen, Rui Zhang, Yang Lv, Junnian Zhou, Xue Nan, Lijuan He, Wen Yue, Yanhua Li, Xuetao Pei
Journal: Blood (2013)
Extralymphatic virus sanctuaries as a consequence of potent T-cell activation
Authors: Mike Recher, Karl S Lang, Alexander Navarini, Lukas Hunziker, Philipp A Lang, Katja Fink, Stefan Freigang, Panco Georgiev, Lars Hangartner, Raphael Zellweger, Andreas Bergthaler, Ahmed N Hegazy, Bruno Eschli, Alexandre Theocharides, Lukas T Jeker, Doron Merkler, Bernhard Odermatt, Martin Hersberger, Hans Hengartner, Rolf M Zinkernagel
Journal: Nature Medicine (2007)
A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.
Authors: M J Gannon, E M Holt, J Fairbank, M Fitzgerald, M A Milne, A M Crystal, J O Greenhalf
Journal: BMJ (1991)

<h3>Abstract</h3> Metastasis is orchestrated by phenotypic and metabolic reprogramming underlying tumor aggressiveness. Redox signaling by mammary tumor knockdown (KD) of the antioxidant glutathione peroxidase 2 (GPx2) enhanced metastasis via dynamic changes in epithelial-to-mesenchymal transition. Single cell RNA sequencing (scRNA-seq) of the control and PyMT/GPx2 KD mammary tumor revealed six luminal and one basal/mesenchymal like (cluster 3) subpopulations. Remarkably, GPx2 KD enhanced the size and basal/mesenchymal gene signature of cluster 3 as well as induced epithelial/mesenchymal (E/M) clusters which expressed markers of oxidative phosphorylation and glycolysis, indicative of hybrid metabolism. These data were validated in human breast cancer xenografts and were supported by pseudotime cell trajectory analysis. Moreover, the E/M and M states were both attenuated by GPx2 gain of function or HIF1α inhibition, leading to metastasis suppression. Collectively, these results demonstrate that redox/HIF1α signaling promotes mesenchymal gene expression, resulting in E/M clusters and a mesenchymal root subpopulation, driving phenotypic and metabolic heterogeneity underlying metastasis. <h3>Significance</h3> By leveraging single cell RNA analysis, we were able to demonstrate that redox signaling by GPx2 loss in mammary tumors results in HIF1α signaling, which promotes partial and full EMT conversions, represented by distinct tumor cell subpopulations, which in turn express hybrid and binary metabolic states. These data underscore a phenotypic and metabolic co-adaptation in cancer, arguing in favor of the GPx2-HIF1α axis as a therapeutic platform for targeting tumor cell metastasis.
What do non-eosinophilic asthma and airway remodelling tell us about persistent asthma?
Authors: P. G Gibson
Journal: Thorax (2007)

Laser therapy offers rapid relief of dysphagia for patients with cancers of the oesophagus and gastric cardia but repeat treatments are required approximately every five weeks to maintain good swallowing. To try to prolong the treatment interval, 22 elderly patients were given additional external beam radiotherapy. Nine had squamous cell carcinoma and 13 adenocarcinoma: five had documented metastases. Six received 40 Gy and 16,30 Gy in 10-20 fractions. A 9check9 endoscopy was performed three weeks after external beam radiotherapy. Dysphagia was graded from 0-4 (0 = normal; 4 = dysphagia for liquids). The median dysphagia grade improved from 3 to 1 after laser treatment. This improvement was maintained in the 30 Gy group but there was a noticeable deterioration in three of those who had received the higher radiation dose. A lifelong dysphagia grade of 2 or better was enjoyed by 14 of 16 patients in the 30 Gy group but only two of six in the 40 Gy group. The dysphagia controlled interval was 9 weeks (median) after check endoscopy and subsequent endoscopic procedures were required every 13 weeks to maintain good swallowing. There were no endoscopy related complications. Combined treatment is a promising approach for reducing the frequency of endoscopic treatments. The 30 Gy dose seems more appropriate and may prolong survival. A randomised study to test these conclusions is in progress.
Abstract 4985: Cellular dormancy in residual disease following oncogene inhibition
Authors: Jason Ruth, Dhruv Pant, Blaine Keister, Christopher Sterner, Lewis Chodosh
Journal: Cancer Research (2014)

Abstract Tumor recurrence is the primary cause of cancer-related mortality. Recurrent tumors arise from residual cancer cells surviving treatment of the primary tumor. It remains unclear whether residual tumor cells are quiescent, or whether they are proliferative but tumor recurrence is limited by a countervailing level of cell death, due to insufficient vascularization or an inhospitable microenvironment. Using inducible models for HER2/neu and Wnt1 mammary tumorigenesis, we found that residual tumor cells surviving oncogene inhibition are quiescent, and reside in a desmoplastic and well-vascularized microenvironment. We confirmed these results by performing gene expression analysis on residual tumor cells, primary tumor cells, recurrent tumor cells, and stromal cells. Gene ontology analysis identified dramatic downregulation of gene clusters associated with proliferation in dormant residual tumor cells compared to all other cell types. Genes we identified as up- or downregulated in dormant residual disease were identified in other models of dormancy, suggesting generalizable mechanisms underpinning dormancy in different contexts. Dormancy-specific changes in additional genes further suggest a role for both EMT and stem cell-related signaling in dormant residual disease which survives targeted therapy. Finally, we demonstrated quiescent residual disease in a xenograft model of breast cancer treated with clinically relevant targeted therapies. In summation, these results suggest both that residual disease may exhibit cellular dormancy following targeted therapy, and that some mechanisms regulating cellular quiescence may be similar across different contexts. Citation Format: Jason Ruth, Dhruv Pant, Blaine Keister, Christopher Sterner, Lewis Chodosh. Cellular dormancy in residual disease following oncogene inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4985. doi:10.1158/1538-7445.AM2014-4985
Anaemia of the Optic Nerves Treated by Galvanism
Authors: R. J. Pye-Smith
Journal: BMJ (1872)

degree than in the former case, and without the characteristic scarlet rash; and, on removing the plaster, she was soon all right."The same journal (November 24th, I866) relates from the London Hospital Reports two cases of poisoning by the external application of belladonna."The first was that of a nobleman, for whom a liniment containing two drachms of liquor belladonnve in two ounces of soap liniment had been ordered.After using it, he hastily sum- moned his physician, who found him with widely dilated pupils, cerebral excitement, and rapid pulse.Another liniment, without the belladonna, was prescribed, and the doctor left.The next day, be was again hastily summoned, and found his patient with a solicitor, three keepers, and a 'mad doctor', who had already signed a certifi- cate of insanity.It turned out that the liniment containing belladonna had, by mistake, been applied a second time; and hence a return of the cerebral excitement, rather exaggerated.Dr. Brown explained that the patient's state was attributable to the belladonna, and that the symptoms would speedily disappear, as indeed they did."Another case is related by Dr. Fraser, of a servant girl who was taken to the London Hospital by her mistress, " who was afraid the girl was going out of her mind.The girl was extremely restless; would wander about the room; stand first on one foot, and then on the other; but was quiet for a moment when spoken to, and answered a question with an effort, generally breaking off in the middle, as if she had forgotten what she had to say.It was noticed at once that her
Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia
Authors: Pekka Jaako, Johan Flygare, Karin Olsson, Ronan Quere, Mats Ehinger, Adrianna Henson, Steven Ellis, Axel Schambach, Christopher Baum, Johan Richter, Jonas Larsson, David Bryder, Stefan Karlsson
Journal: Blood (2011)
Deus Ex Machina in Perspective
Authors: Daniel K. Harris
Journal: JAMA (1976)

In his August 16, 1976,<i>JAMA</i>editorial entitled, "Are Medical Schools Neglecting Clinical Skills?" George L. Engel, MD, suggests that the clinical acumen of recent medical school graduates suffers substantially due to reliance upon technological support mechanisms.<sup>1</sup>The debate concerning clinical and economic efficacy of technologic innovation has become intense in recent times, particularly as legislation holds the promise of transferring control over medical technology from the medical environment to governmental bureaucracy. To the debate, Dr Engel adds the concern that technology has eroded the clinician's ability to render sound, intellectual judgment. Reliance upon a computer or other mechanical contrivances to develop clinical data may portend the diminution of clinical skills, and there may be the potential for educational deficits concerning the<i>conceptual</i>determinants upon which mechanized clinical data development is predicated. However, to impute causality for these prospects to an overabundance of technology represents a non sequitur that
Factors that influence patients in Sri Lanka in their choice between Ayurvedic and Western medicine.
Authors: J R Glynn, T D Heymann
Journal: BMJ (1985)

Patients in Sri Lanka can choose between two main types of medicine, Western ("English") and traditional (Ayurvedic); both are supported by the government.Surprisingly, the factors that influence patients in their choice are little known.'In 1983 we spent five weeks in Sri Lanka trying to discover what these factors might be.We studied two main areas, the village of Denipitiya in the south and the small town of Talawa in the North Central Province, interviewing doctors and patients in both places as well as in larger hospitals elsewhere.Precise figures for the racial composition of the populations of Denipitiya and Talawa are not available, but according to a census carried out in 1981 the compositions of the two administrative districts that include these centres are roughly similar, with over 90% Sinhalese (predominantly Buddhist) and the remainder split between Tamils (predominantly Hindu) and Sri Lanka Moors (Moslem). AyurvedaAyurveda is based on a humoral theory like that of the ancient Greeks-possibly even predating it2-and, similarly, aims to balance the humours using methods of elimination.These methods, known collectively as "puncturekarma," include the use of purgatives, enemas ("to rejuvenate the body"), emetics, nasal oils to remove phlegm, and bloodletting.In addition, oil baths, internal herbal medicines, and special diets are used, all in a strict regimen.34The preparation for puncturekarma includes sudation in a sauna, a hip bath in herbal water, and a series of oil massages.For example, the regimen used at the Central Ayurvedic Hospital in Colombo to treat asthma is: ghee in increasing doses with a vegetarian diet, sudation on the seventh day, emetics on the ninth day until the patient has vomited seven times, and a special diet for several weeks.Ayurveda is based on an unhurried approach; it cannot be used to treat emergencies and no longer includes surgery.Each treatment in hospital lasts for at least one month with the result that few patients attend the Ayurvedic hospital first; most go only as a last resort.The wards of the Ayurvedic hospitals are not unlike those in the government "Western" hospitals, but the drug store in the Central Ayurvedic Hospital is more like a spice shop than a pharmacy, with sacks full ofherbs, and mixtures and powdered drugs in a chaos of old bottles and containers.In the "kitchen" there are rows of saucepans of medicines on the boil tended by men stripped to the waist, who are barely discernible through the steam.In another room fermented medicines similar to wine are stored in huge Ali Baba jars.Ayurveda is less well supported by the government than Western medicine, with only two schools and an extramural qualifying examination compared with four government schools for Western medicine.The course in Ayurveda lasts five years, and the staff of the Institute of Indigenous
Accidental hypothermia and low-reading thermometers.
Authors: E L Lloyd, K Little
Journal: BMJ (1979)

brought to hospital having been found unconscious at home after sniffing Evostik glue.Almost immediately on arrival at hospital he had a typical grand mal convulsion, which was controlled by 5 mg of diazepam given intravenously.He regained consciousness after 20 minutes and was detained in hospital for four days.Investigations revealed no evidence of hepatic or renal dysfunction and he was subsequently discharged home.It is not known whether this patient had indulged in glue sniffing in the past.
Relative contributions of history-taking, physical examination, and laboratory investigation to diagnosis and management of medical outpatients.
Authors: J R Hampton, M J Harrison, J R Mitchell, J S Prichard, C Seymour
Journal: BMJ (1975)

To evaluate the relative importance of the medical history, the physical examination, and laboratory investigations in the diagnosis and management of medical outpatients some physicians recorded their diagnosis and a prediction of the method of managementafter reading the patient9s referral letter, again after taking the history, and againafter performing the physical examination. These diagnoses and predictions were compared with the diagnosis and method of management which had been adopted two months after the patient9s initial attendance. A diagnosis that agreed with the one finally accepted was made after reading the referral letter and taking the history in 66 out of 80 new patients; the physical examination was useful in only seven patients, and the laboratory investigations in a further seven. In only one of six patients in whom the physician was unable to make any diagnosis after taking the history and examining the patient did laboratory investigations lead to a positive diagnosis.
599 Peg-IFN plus ribavirin therapy suppresses plasma TGF-β1, hyaluronic acid and procollagen-III-peptide levels in patients with chronic hepatitis C independently of virological response
Authors: A. Par, G. Par, T. Berki, A. Miseta, G. Hegedûs, Gy. Mózsik, B. Hunyady
Journal: Journal of Hepatology (2006)
Weight loss in obese subjects on a restricted diet given BRL 26830A, a new atypical adrenoceptor agonist
Authors: A A Connacher, R T Jung, P E G Mitchell
Journal: BMJ (1988)

A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic β adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3·35 MJ diet that was low in fat and high in fibre. Weight loss was 15·4 (SD 6·6) kg in subjects given BRL 26830A compared with 10·0 (5·9) kg in those given placebo (p=0·02). The relative weight loss was 0·93 (0·39)% a week with BRL 26830A and 0·61 (0·38)% with placebo (p=0·02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4·1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11·6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically. BRL 26830A may be a useful drug in the treatment of obesity.
Thyroxine-induced hypertrophy of the rabbit heart. Effect on regional oxygen extraction, flow, and oxygen consumption.
Authors: K Talafih, K L Briden, H R Weiss
Journal: Circulation Research (1983)

The effects of the administration of 0.5 or 1 mg/kg of 1-thyroxine for 3 or 16 days were studied in 55 New Zealand white rabbits. Heart size was 29% above control after 16 days of 1-thyroxine, despite lower body weights. In an anesthetized open-chest animal, regional microspectro-photometric observations of small arteries and veins to determine oxygen extraction were combined with regional blood flow measurements using radioactive microspheres to determine regional oxygen consumption by the Fick principle. Vascular flow reserves were studied through measurement of blood flow after the administration of chromonar HCl, 10 mg/kg. Myocardial oxygen consumption was, respectively, 2.4 and 3.8 times control after 3 and 16 days of 1-thyroxine. This was accompanied by significant increases in both coronary blood flow and oxygen extraction. In control, oxygen extraction and consumption were higher in the subendocardial region compared to the subepicardial area. No significant regional differences were found in flow, oxygen extraction, or consumption after 1-thyroxine administration. Chromonar increased coronary blood flow 2.8 times in the control animals, but did not significantly increase flow or decrease vascular resistance in the rabbits given 1-thyroxine. Adenosine increased coronary blood flow 3.5 times in the control animals but only 2.2 times in animals given 1-thyroxine for 3 days. Animals given 1-thyroxine had hypertrophied hearts with increased oxygen consumption, markedly increased flow, and increased oxygen extraction but without regional left ventricular differences.