tbuckley/cabot-search huggingface dataset:
Extracellular K <sup>+</sup> Dependence of Inward Rectification Kinetics in Human Left Ventricular Cardiomyocytes
Authors: Patrick Bailly, Maud Mouchonière, Jean-Pierre Bénitah, Lionel Camilleri, Guy Vassort, Paco Lorente
Journal: Circulation (1998)

Background —In human ventricular cells, the inwardly rectifying K + current ( I K1 ) is very similar to that of other mammalian species, but detailed knowledge about the K + -dependent distribution of open and blocked states during rectification and about the K + -dependent modulation of inactivation on hyperpolarization is currently lacking. Methods and Results —We used the whole-cell patch-clamp technique to record I K1 in myocytes isolated from subendocardial layers of left ventricular septum from patients with nonfailing hearts with aortic stenosis and cardiac hypertrophy who were undergoing open-heart surgery. Outward currents were very small at voltages positive to the reversal potential but increased at high external [K + ]. Chord conductance measurements and kinetic analyses allowed us to estimate the proportion of channels in the open state and of those showing either slow unblock or instantaneous unblock (the so-called slow or instantaneous “activation”) on hyperpolarization: the distribution in the individual states was dependent on external [K + ]. The proportion of channels unblocking slowly was greater than that of channels unblocking instantaneously on hyperpolarization from the plateau voltage range. Hence, because of the previously reported link between the presence of highly protonated blocking molecules and slow unblock kinetics, it is suggested that high cellular concentrations of spermine may account for the low outward current density recorded in these cells. The current decrease observed on extended hyperpolarization was significantly relieved by an increase in external [K + ]. Conclusions —The pattern of I K1 current alterations observed in the present model of human ventricular hypertrophy might favor enhanced excitability and underlie ventricular arrhythmias, possibly via increased intracellular polyamine levels.
PET/CT Demonstration and Monitoring of Thoracic and Abdominal Wall Mesothelioma
Authors: Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2013)

Mesothelioma is a malignancy arising from the embryonic coelomic mesodermal lining forming the pleura, peritoneum, pericardium, and tunica vaginalis. It is mostly induced by exposure to asbestos. The author presents a 77-year-old woman with an atypical manifestation of epithelioid mesothelioma, which does not follow the expected clinical characteristics of this disease mentioned above. In this case, PET/CT provides useful information concerning the extension of the lesions to thoracic and abdominal walls not fully evaluated by the initial conventional cross-sectional imaging. PET/CT also allows an accurate therapeutic monitoring of the disease.
A STUDY OF THE BACTERIAL FLORA OF THE NASAL MUCOSA IN THE PRESENCE OF RHINITIS
Authors: WILL WALTER
Journal: JAMA (1910)

IV. CASES NOT YIELDING TKYPTOl'IIAN REACTION None of the cases in this group gave the tryptophan reac¬ tion.The tryptophan test was repeated several times in many cases.The gastric contents from all these cases had free hydrochloric acid.Six cases of hyperacidity.Three cases of chronic gastric ulcer.Five cases of neurasthenia.One case of contraction of gastro-enterostomic orifice four years after operation.Marked stasis of food.Dilated stomach.One ease of arteriosclerosis.One case of hyporncphroina.Patient died.Three cases of gastric atony, with marked stasis of food.Two cases of gtistroptosis.One case of enlarged gall-bladder, probably due to calculi.One case of chronic constipation.71 East Ninety-sixth Street.
Long-lived intestinal tuft cells serve as colon cancer–initiating cells
Authors: C. Benedikt Westphalen, Samuel Asfaha, Yoku Hayakawa, Yoshihiro Takemoto, Dana J. Lukin, Andreas H. Nuber, Anna Brandtner, Wanda Setlik, Helen Remotti, Ashlesha Muley, Xiaowei Chen, Randal May, Courtney W. Houchen, James G. Fox, Michael D. Gershon, Michael Quante, Timothy C. Wang
Journal: Journal of Clinical Investigation (2014)

Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth-sustaining stem cells. DCLK1⁺ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT-dependent genetic lineage-tracing strategy, we determined that a subpopulation of DCLK1⁺ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1⁺ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1⁺ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate-induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1⁺ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1⁺ cells. Thus, our data define an intestinal DCLK1⁺ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1⁺ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer.
Strain induced augmentation of upper oesophageal sphincter pressure in children.
Authors: J Willing, Y Furukawa, G P Davidson, J Dent
Journal: Gut (1994)

The hypothesis that troublesome oesophagopharyngeal reflux arises from defective upper oesophageal sphincter response to straining has been evaluated in 53 children aged two to 81 months (median 13) referred with symptoms thought to be related to gastro-oesophageal reflux. Spontaneously occurring pharyngeal, upper oesophageal sphincter, oesophageal body, and gastric pressures were analysed after feeding. Inspiratory strain was the most common spontaneously occurring strain (172 episodes), defined as an oesophageal body inspiratory negative pressure dip at least twice the size of the normal inspiratory wave. Overall, during inspiratory strain, upper oesophageal sphincter pressure was significantly higher than before straining (p &lt; 0.01) (5 v 27 mm Hg, p &lt; 0.01). Sustained strains defined as increases in gastric and oesophageal body pressure for two to 20 seconds were also common (149 episodes) and when compared with just before straining, also augmented upper oesophageal sphincter pressure (60 v 39 mm Hg, p &lt; 0.01). The vigour of straining, estimated as increase of gastric pressure, correlated significantly with the degree of augmentation of upper oesophageal sphincter pressure (p &lt; 0.05). Children with and without evidence of troublesome oesophagopharyngeal reflux showed no difference in upper oesophageal sphincter response patterns to straining. Failure of augmentation of upper oesophageal sphincter tone in the face of strain induced increases of oesophageal body pressure is probably a secondary factor in the production of oesophagopharyngeal reflux in children.
Contempo: ethical issues of human embryos research and physician-assisted suicide
Authors: C. A. Tauer
Journal: JAMA (1995)

To  Editor.  —In his recent Comtempo article on ethics, Dr Pellegrino 1 asserted: Late in 1994, two previously impassable ethical barriers were crossed in  United States... for  first time, a National Institutes of Health [NIH] advisory panel approved funding for  production of  embryos for research purposes.  Pellegrino is incorrect. The Ethics Advisory Board (EAB) appointed in 1978 by  US Department of Health, Education, and Welfare also approved  creation of  embryos for research under stipulated conditions. 2 The EAB report stated that human in vitro fertilization research without embryo transfer is ethically acceptable provided that the research is designed primarily to establish  safety and efficacy of embryo transfer and that human gametes used in such research will be obtained exclusively from persons who have been fully informed and have explicitly consented.  Whatever one's moral views about  acceptability of such research, it
Hugh Clegg: recollections of a great editor.
Authors: A B Hill
Journal: BMJ (1990)

In writing these memories of my friendship with Hugh Clegg I must of course be autobiographical.I do not remember when I first met him, and I shall deliberately go back to the years when I am sure I had not-the mid-1920s.While convalescing after my long attack of tuber- culosis I had read economics, and I took the London University degree in that subject in 1922.I then got a grant from the Medical Research Council.Barred from clinical medicine, I determined to make a life in preventive medicine.For medical reading I naturally turned to the Lancet-the BM7, as Hugh once said to me, "spent half
Fluosol-DA as a Red-Cell Substitute in Acute Anemia
Authors: Steven A. Gould, Arthur L. Rosen, Lakshman R. Sehgal, Hansa L. Sehgal, Lorrie A. Langdale, Lawrence M. Krause, Charles L. Rice, William H. Chamberlin, Gerald S. Moss
Journal: New England Journal of Medicine (1986)

We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (+/- SE) of 7.2 +/- 0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0 +/- 0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7 +/- 0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3 +/- 4.3 hours), and the limited total dose. Six of the eight patients receiving Fluosol-DA died. One of the survivors received red-cell transfusions against his wishes, under a court order, after his total Fluosol-DA dose. Fourteen of the 15 moderately anemic patients survived. The data in this select group of patients refusing blood products suggest that, after blood loss, Fluosol-DA is unnecessary in moderate anemia and ineffective in severe anemia.
Paradox of vaccination in cervical cancer and screening
Authors: C. A Gericke
Journal: BMJ (2008)

The development of human papillomavirus (HPV) vaccines and their potential for reducing cervical cancer incidence and mortality is generally considered an important step to improve population health worldwide. For countries without well performing cervical cancer screening programmes and lack of treatment options the current epidemiological and economic models seem applicable.

However, the assumptions underlying published …
Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.
Authors: R Yung, D Powers, K Johnson, E Amento, D Carr, T Laing, J Yang, S Chang, N Hemati, B Richardson
Journal: Journal of Clinical Investigation (1996)

Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.
Occurrence of cadmium in crabs (Cancer pagurus) and the isolation and properties of cadmium metallothionein.
Authors: J Overnell
Journal: Environmental Health Perspectives (1986)

The occurrence of high cadmium levels in the digestive gland (hepatopancreas) of the crab Cancer pagurus is reviewed and its possible significance to human health is discussed. Previous attempts to isolate this cadmium in its native form are briefly reviewed and the present method used in this laboratory to isolate crab cadmium metallothionein is described. Quantitative amino acid analysis of the purified protein suggests that it has a total of 55 residues, including 19 Cys, and a molecular weight of approximately 5800. This yields an extinction coefficient at 220 nm for the protein in HCl, pH 1.5, of 50,000 and at 250 nm for the native cadmium protein in Tris-HCl, pH 8.4, of 92,000.
Previous-beat contraction history is not influenced by mechanosensitive ion channel blockade
Authors: B. K. Slinker, A. H. Tobias
Journal: Cardiovascular Research (1996)

Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history". This previous-beat contraction history, which appears to be an interplay between the mechanical events of one contraction and the activation state of the next contraction, could depend, at least in part, on mechanosensitive ion channels. The purpose of this study, therefore, was to test the hypothesis that mechanosensitive ion channels contribute to previous-beat contraction history: If previous-beat contraction history depends on mechanosensitive ion channels, the magnitude of its effect should be decreased by blocking mechanosensitive ion channels.We performed experiments in buffer-perfused isolated rabbit hearts in which left ventricular pressure and volume were controlled with a servo-motor system. We evaluated the pulse interval-dependent expression of previous-beat contraction history under control conditions (no drug) and in the presence of 100 and 500 microM streptomycin, a blocker of mechanosensitive ion channels.Under control conditions, previous-beat contraction history nor its dependence on pulse interval was influenced significantly by either concentration of streptomycin.Mechanosensitive ion channels do not play a role in the expression of previous-beat contraction history in the left ventricle of the isolated rabbit heart.
Expression of cell–cell interacting genes distinguishes HLXB9/TEL from MLL-positive childhood acute myeloid leukemia
Authors: S Wildenhain, C Ruckert, S Röttgers, J Harbott, W-D Ludwig, F R Schuster, K Beldjord, V Binder, R Slany, J Hauer, A Borkhardt
Journal: Leukemia (2010)
Re: Daher C. Chade, Shahrokh F. Shariat, Angel M. Cronin, et al. Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration. Eur Urol 2011;60:205–10
Authors: XiaoJian Qin, DingWei Ye
Journal: European Urology (2011)
Kenneth Dickson Jones
Authors: V. H. Needham
Journal: BMJ (2011)

Kenneth Dickson Jones (“Ken”) attended Dundee High School, where he excelled at rugby, and qualified from Dundee University in 1979, by which time he was also an experienced and highly competent mountaineer. He served in the Royal Army Medical Corps in Germany, the UK, the Falklands (in the immediate aftermath of conflict), Canada, …
Major chemical disasters.
Authors: M Harrison, T C Aw, G Krishnan, A F Jones, J A Vale
Journal: BMJ (1991)

exercise tests where there is no contraindication.We use (i blockers in addition to aspirin in patients with hypertension and angina and consider them in those whom we assess to be at high risk.In the remaining asymptomatic low risk group we do not think that the potential additional benefit from 0 blockers justifies their use.The potential side
A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma
Authors: Carlos A. Camargo, Deborah M. Gurner, Howard A. Smithline, Rocio Chapela, Leonardo M. Fabbri, Stuart A. Green, Marie-Pierre Malice, Catherine Legrand, S. Balachandra Dass, Barbara A. Knorr, Theodore F. Reiss
Journal: Journal of Allergy and Clinical Immunology (2010)
A core set of trial outcomes for every medical discipline?
Authors: W. Koroshetz
Journal: BMJ (2015)

An important step towards truly meaningful “big data”

The linked article by Ioannidis and colleagues (doi:10.1136/bmj.h72) asks two important questions: should each medical discipline reach a consensus on whether certain outcomes are important regardless of which intervention is being tested? And, once these are established, should there be a requirement that trials routinely collect information and report this set of core outcomes in a standardized fashion?1

The authors examined all available systematic reviews of treatments in premature infants and found what they consider to be “errors of omission” of respiratory outcomes in a large percentage of systemic reviews and clinical studies. To simplify, the authors argue that even though there are a host of clinical research questions that need answers to improve the care of premature infants, respiratory outcomes are so important that they should be included in all studies, whether the focus is on nutritional, endocrine, neurological, hematological, or other body systems.

The generic issue of establishing and requiring core outcomes to enable combination of data from multiple studies is critical. The message is similar to the one fashioned by the Core Outcome Measures …
General Pathology Based on Lectures Delivered at the Sir William Dunn School of Pathology, University of Oxford
Authors: A. P. Hovnanian
Journal: JAMA (1962)

The modern science of pathology was born in 1858 when Rudolf Virchow published his<i>Cellular Pathologie</i>. From this date to the early '20's of the present century, the multiple contributions to pathology have been mainly in the field of morphology; the last and most important event in that field being the advent of electron microscopy. However, in the last 25 years other facets in pathology are being highlighted. Great impetus is given to the biochemical, enzymatic, and functional aspects of the body tissues. Actually a third dimension is added to pathology with cellular microchemistry, investigation of enzyme systems, immune reactions, radiation effects, tissue transplantation phenomena, and allergic manifestations. Sir Howard Florey's book on general pathology must be appraised against this background. This text is a compilation of lectures that have been delivered to the Oxford University medical students who are enrolled in the Honour School of Physiology, where a good
Drug company settles over antibiotic claim
Authors: F B Charatan
Journal: BMJ (1994)

The drug company Hoffmann-La Roche has agreed to pay the US Department of Health and Human Services (DHHS) $450 000 (pounds sterling300 000) to settle allegations of improper inducements to doctors and pharmacists to prescribe Rocephin (ceftriaxone), an antibiotic. An anti-kickback law prohibits the use of financial inducements to influence prescribing of products or services covered by Medicare and Medicaid, the federally funded health programmes.

The compromise settlement, which involved no admission of wrongdoing or liability by the …
Activation of Human Long Interspersed Nuclear Element 1 Retrotransposition by Benzo(<i>a</i>)pyrene, an Ubiquitous Environmental Carcinogen
Authors: Vilius Stribinskis, Kenneth S. Ramos
Journal: Cancer Research (2006)

Abstract Long interspersed nuclear elements [LINE-1 (L1)] are abundant retrotransposons in mammalian genomes that remain silent under most conditions. Cellular stress signals activate L1, but the molecular mechanisms controlling L1 activation remain unclear. Evidence is presented here that benzo(a)pyrene (BaP), an environmental hydrocarbon metabolized by mammalian cytochrome P450s to reactive carcinogenic intermediates, increases L1 retrotransposition in HeLa cells. Increased retrotransposition is mediated by up-regulation of L1 RNA levels, increased L1 cDNA synthesis, and stable genomic integration. Activation of L1 is dependent on the ability of BaP to cause DNA damage because it is absent in HeLa cells challenged with nongenotoxic hydrocarbon carcinogens. Thus, the mutations and genomic instability observed in human populations exposed to genotoxic environmental hydrocarbons may involve epigenetic activation of mobile elements dispersed throughout the human genome. (Cancer Res 2006; 66(5): 2616-20)
Explore the humanities in illness and medicine
Authors: G. Watts
Journal: BMJ (2009)

With a nascent research programme ranging from an analysis of 15 000 sets of psychiatric case notes to a philosophical enquiry into the very concept of health, the newly inaugurated Centre for the Humanities and Health is aiming to tackle its subject material on a broad front. A virtual organisation based at King’s College London and established with a grant of £2m (€2.2m; $3.3m) from the Wellcome Trust, it will study illness not as biomedical phenomenon but as a subjective experience to be scrutinised by scholars from King’s and elsewhere, with backgrounds in history, literature, psychology, philosophy, and the visual and other arts as well as nursing and medicine.

The director of the centre is Brian Hurwitz, D’Oyly Carte professor of medicine and the arts at King’s, and an inner London GP. His own interest in the topic goes back to the time when he was still in training. He became intrigued by the complexity of communication between doctors and patients and their often differing frames of reference. This led to an interest in narratives in medicine then to its links with the arts and now to much wider connections with all the humanities.

One of the centre’s intentions is to set up a masters course. Enrolment will not begin until next year, so at this stage Professor …