tbuckley/cabot-search huggingface dataset:
Screening of colorectal tumours using an improved faecal occult blood test. Quantitative aspects.
Authors: I Hakkinen, R Paasivuo, P Partanen
Journal: Gut (1988)

A recently developed double test for detecting faecal occult blood (a sensitive guaiac test combined with a quantitative immunological human haemoglobin test), was adapted to population screening. The study involved an unselected population of 10,343, aged 49-74 years. There was 66.5% participation. 174 colonoscopies were done, yielding seven adenocarcinomas, 44 adenomas and four hyperplastic polyps. By eliminating benign anal tract bleeding, the number of endoscopies decreased from 340 to 174. Most tumours showed an absorbance over 0.80, and it is suggested that by setting the lower limit of positivity at the 0.80 absorbance level, the number of clinical examinations could fall to about 1%, without substantially missing tumours.
A Double-Blind Study of the Effect of Ribonucleic Acid in Senile Brain Disease
Authors: JOHN H. NODINE, MARK W. SHULKIN, JOSEPH W. SLAP, MURRAY LEVINE, KENNETH FREIBERG
Journal: American Journal of Psychiatry (1967)

A double-blind study to test the effect of orally administered ribonucleic acid upon the course of senile and arteriosclerotic brain disease failed to confirm the positive findings of other investigators. The authors conclude that RNA administered in this form does not appear to bring about improvement or reversal of senile brain disease.
Two types of Zollinger-Ellison syndrome: immunofluorescent, cytochemical and ultrastructural studies of the antral and pancreatic gastrin cells in different clinical states
Authors: J. M. Polak, B. Stagg, A. G. E. Pearse
Journal: Gut (1972)

In this survey the antral, pancreatic and, where present, the neoplastic gastrin cells, were studied in eight cases of the Zollinger-Ellison syndrome. The antral G cells alone were studied in one case of Z-E syndrome, seven cases of simple duodenal ulcer, and five cases of pernicious anaemia. The Z-E cases were divided into two numerically equal groups. The first group had ;short' histories, high serum gastrin levels, and profound antral G cell hyperplasia. The second group had ;long' histories, relatively lower serum gastrin levels, normal antral G cells, and either pancreatic D cell hyperplasia or gastrinoma. Antral G cell hyperplasia, with maximal gastrin storage and normal serum gastrin levels, was found in the duodenal ulcer cases. Antral G cell hyperplasia with minimal storage and high serum gastrin levels was observed in the cases of pernicious anaemia. On the basis of our findings we propose that there exist at least two distinct types (or perhaps stages) of the Z-E syndrome. Suggestions for their pathogenesis are offered.
Effect of thromboxane A2 synthetase inhibitor, OKY-046, on sputum in chronic bronchitis and diffuse panbronchiolitis
Authors: K Kurashima, M Fujimura, Y Hoyano, K Takemura, T Matsuda
Journal: European Respiratory Journal (1995)

The mechanisms of excessive sputum production are only partially understood. We speculated that a selective thromboxane (Tx) A2 synthetase inhibitor, OKY-046, now used in the treatment of asthma in Japan, could decrease excess sputum production in patients with chronic airways disease. To test this hypothesis, we carried out a double-blind, placebo-controlled study of the effects of OKY-046, administered orally at 400 mg.day-1, on the sputum of patients with chronic bronchitis and patients with diffuse panbronchiolitis. Patients treated with OKY-046 showed a significant decrease (22%) in sputum volume after 1 month, and a 39% decrease after 3 months. Although the rheological properties of the sputum and the concentrations of fucose and immunoglobulin (Ig) A in the sputum remained unchanged, significant decreases were observed in the concentrations of total protein, albumin, sialic acid and phospholipid. Since albumin and fucose are chemical markers of plasma exudation and mucus secretion, respectively, whilst sialic acid and phospholipid are derived both from serum and mucus, our results indicate that this TxA2 synthetase inhibitor reduced sputum volume by inhibiting microvascular leakage in the airway. OKY-046 may, therefore, be of value in the treatment of chronic bronchitis and diffuse panbronchiolitis.
Discovery and Canine Preclinical Assessment of a Nontoxic Procaspase-3–Activating Compound
Authors: Quinn P. Peterson, Danny C. Hsu, Chris J. Novotny, Diana C. West, Dewey Kim, Joanna M. Schmit, Levent Dirikolu, Paul J. Hergenrother, Timothy M. Fan
Journal: Cancer Research (2010)

Abstract A critical event in the apoptotic cascade is the proteolytic activation of procaspases to active caspases. The caspase autoactivating compound PAC-1 induces cancer cell apoptosis and exhibits antitumor activity in murine xenograft models when administered orally as a lipid-based formulation or implanted s.c. as a cholesterol pellet. However, high doses of PAC-1 were found to induce neurotoxicity, prompting us to design and assess a novel PAC-1 derivative called S-PAC-1. Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell apoptosis. However, S-PAC-1 did not induce neurotoxicity in mice or dogs. Continuous i.v. infusion of S-PAC-1 in dogs led to a steady-state plasma concentration of ∼10 μmol/L for 24 to 72 hours. In a small efficacy trial of S-PAC-1, evaluation of six pet dogs with lymphoma revealed that S-PAC-1 was well tolerated and that the treatments induced partial tumor regression or stable disease in four of six subjects. Our results support this canine setting for further evaluation of small-molecule procaspase-3 activators, including S-PAC-1, a compound that is an excellent candidate for further clinical evaluation as a novel cancer chemotherapeutic. Cancer Res; 70(18); 7232–41. ©2010 AACR.
Incidence and Risk Factors of Prolonged QTc Interval in Type 1 Diabetes
Authors: Sara Giunti, Graziella Bruno, Emma Lillaz, Gabriella Gruden, Valentina Lolli, Nish Chaturvedi, John H. Fuller, Massimo Veglio, Paolo Cavallo-Perin
Journal: Diabetes Care (2007)

Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and diabetic populations. As part of the EURODIAB Prospective Complication Study, we have assessed the 7-year incidence and risk factors of prolonged QTc in people with type 1 diabetes.A total of 1,415 type 1 diabetic subjects, who had normal QTc at baseline, were reanalyzed after the 7-year follow-up period. QTc >0.44 s was considered abnormally prolonged.Cumulative incidence of prolonged QTc was 18.7%, which is twofold higher in women than in men (24.5 vs. 13.9%, P < 0.0001). At the baseline examination, incident cases were older and less physically active than nonincident cases, had higher mean values of systolic blood pressure and HDL cholesterol, and had higher frequencies of hypertension, coronary heart disease, and distal symmetrical polyneuropathy. In multivariate logistic regression analyses, female sex and higher values of A1C and systolic blood pressure were associated with the risk of prolonged QTc, whereas physical activity and BMI within the range of 21.5-23.2 kg/m2 were protective factors. In women, association with modifiable factors, particularly BMI, was stronger than in men.In type 1 diabetic subjects from the EURODIAB cohort, female sex, A1C, and systolic blood pressure are predictive of prolonged QTc, whereas physical activity and BMI within the range of 21.5-23.2 kg/m2 play a protective role. These findings are clinically relevant, as they may help to identify subjects at higher risk for prolonged QTc, as well as provide potential targets for risk-lowering strategies.
Diphenylhydantoin as an Antiarrhythmic Drug
Authors: A J Atkinson, R Davison
Journal: Annual Review of Medicine (1974)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Morphological Changes in Dendritic Spines Associated with Long-Term Synaptic Plasticity
Authors: Rafael Yuste, Tobias Bonhoeffer
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Dendritic spines are morphological specializations that receive synaptic inputs and compartmentalize calcium. In spite of a long history of research, the specific function of spines is still not well understood. Here we review the current status of the relation between morphological changes in spines and synaptic plasticity. Since Cajal and Tanzi proposed that changes in the structure of the brain might occur as a consequence of experience, the search for the morphological correlates of learning has constituted one of the central questions in neuroscience. Although there are scores of studies that encompass this wide field in many species, in this review we focus on experimental work that has analyzed the morphological consequences of hippocampal long-term potentiation (LTP) in rodents. Over the past two decades many studies have demonstrated changes in the morphology of spines after LTP, such as enlargements of the spine head and shortenings of the spine neck. Biophysically, these changes translate into an increase in the synaptic current injected at the spine, as well as shortening of the time constant for calcium compartmentalization. In addition, recent online studies using time-lapse imaging have reported increased spinogenesis. The currently available data show a strong correlation between synaptic plasticity and morphological changes in spines, although at the same time, there is no evidence that these morphological changes are necessary or sufficient for the induction or maintenance of LTP. Still, they highlight once more how form and function go hand in hand in the central nervous system.
Much ado about bone marrow stem cells: Role in post-myocardial infarct repair
Authors: I DIXON
Journal: Cardiovascular Research (2006)

See article by Mollmann et al.  [14]  (pages 661–671) in this issue. 

The apparent lack of regenerative capacity of cardiac myocytes has, until recently, been upheld in a number of carefully conducted studies [1,2]. Indeed, this supposition has long formed the principal obstacle to the dream of directed repair of the myocardium following massive loss of cardiomyocytes after myocardial infarction (MI). Perhaps this is why the field of experimental cardiology was set upon its ear when a number of studies were presented to challenge this basic premise [3,4]. This work supported the hypothesis that multi-potent bone marrow stem cells (BMSC) were able to migrate to ischemic heart tissue to participate in cardiac regeneration. The usual course of events that transpire following MI manifests as gross alteration of left ventricular geometry involving the altered expression of many hundreds of genes that is collectively referred to as phenotypic plasticity of the myocardium, i.e. cardiac remodelling following injury [5]. The suggestion that cardiomyocytes may regenerate has fueled discussion and investigation to explore the suggestion that the infarct scar might serve as a putative site for regeneration of cardiac muscle. Further work indicated that directed treatments of BMSCs with specific cytokines led to their transdifferentiation to cardiomyocytes at the site of tissues bordering the infarct scar [6], and justifiably, this possibility … 

* Tel.: +1 204 235 3419; fax: +1 204 233 6723. Email address: idixon{at}sbrc.ca
Book: Injury Prevention: An International Perspective
Authors: B. Pless
Journal: BMJ (1998)

Peter Barss, Gordon Smith, Susan Baker, Dinesh Mohan Oxford University Press, £42.50, pp 384 ISBN 0195119827 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Several years ago I reviewed this book in draft form at the request of the publisher. I was torn: it was a labour of love and a potentially important book, but it had numerous shortcomings. I conveyed my concerns but stressed that everything possible should be done to bring it to press. Thankfully, publisher and authors agreed. What we now have is a landmark addition to a remarkably small shelf of texts about this subject. Originally, the book … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Two Functional MicroRNA-126s Repress a Novel Target Gene p21-Activated Kinase 1 to Regulate Vascular Integrity in Zebrafish
Authors: Jun Zou, Wen-Qing Li, Qing Li, Xiang-Qi Li, Jun-Tao Zhang, Gan-Qiang Liu, Jian Chen, Xiao-Xu Qiu, Fu-Ju Tian, Zhi-Zhang Wang, Ni Zhu, Yong-Wen Qin, Bairong Shen, Ting Xi Liu, Qing Jing
Journal: Circulation Research (2010)

Rationale: MicroRNAs (miRNAs) are key regulators of vascular development and diseases. The function and underlying mechanism of endothelial miRNAs have not been fully defined. Objective: To investigate the role of endothelial miR-126 in zebrafish vascular development. Methods and Results: Two homologs of miR-126, miR-126a (namely miR-126 in previous literature) and miR-126b, with only 1 nucleotide difference in their mature sequences, were identified in zebrafish genome. In vitro analysis showed that both precursors could sufficiently produce mature functional miRNAs. Expression analyses by Northern blot and quantitative RT-PCR showed that both miR-126s accumulated significantly 12 hours after fertilization and were specifically expressed in endothelial cells of zebrafish. Inhibition of miR-126a or miR-126b with specific morpholinos caused cranial hemorrhage, and simultaneous inhibition of both miR-126s resulted in a pronounced hemorrhage in higher percentage of embryos. Bioinformatics prediction showed that the targets of miR-126a/b partially overlapped but essentially differed. p21-activated kinase1 ( pak1 ) was identified as a novel target of miR-126a/b, and pak1 3′ untranslated region was differently regulated by these 2 miRNAs. Quantitative RT-PCR, in situ hybridization, and Western blot analyses showed that the level of pak1 was reduced when miR-126a/b were overexpressed. Notably, pak1 expression in endothelial cells was increased when miR-126a/b were knocked down. Furthermore, overexpression of the active form of human pak1 caused cranial hemorrhage, and knockdown pak1 effectively rescued the hemorrhage caused by inhibiting miR-126a/b. Conclusions: Two functional endothelial cell–specific miRNAs, miR-126a and miR-126b, synergistically regulate zebrafish vascular integrity, and pak1 is a critical target of miR-126a/b in vascular development.
Comparison of Transplacental Treatment of Fetal Supraventricular Tachyarrhythmias With Digoxin, Flecainide, and Sotalol
Authors: Edgar T. Jaeggi, Julene S. Carvalho, Ernestine De Groot, Olus Api, Sally-Ann B. Clur, Lukas Rammeloo, Brian W. McCrindle, Greg Ryan, Cedric Manlhiot, Nico A. Blom
Journal: Circulation (2011)

Background— Fetal tachyarrhythmia may result in low cardiac output and death. Consequently, antiarrhythmic treatment is offered in most affected pregnancies. We compared 3 drugs commonly used to control supraventricular tachycardia (SVT) and atrial flutter (AF). Methods and Results— We reviewed 159 consecutive referrals with fetal SVT (n=114) and AF (n=45). Of these, 75 fetuses with SVT and 36 with AF were treated nonrandomly with transplacental flecainide (n=35), sotalol (n=52), or digoxin (n=24) as a first-line agent. Prenatal treatment failure was associated with an incessant versus intermittent arrhythmia pattern (n=85; hazard ratio [HR]=3.1; P &lt;0.001) and, for SVT, with fetal hydrops (n=28; HR=1.8; P =0.04). Atrial flutter had a lower rate of conversion to sinus rhythm before delivery than SVT (HR=2.0; P =0.005). Cardioversion at 5 and 10 days occurred in 50% and 63% of treated SVT cases, respectively, but in only 25% and 41% of treated AF cases. Sotalol was associated with higher rates of prenatal AF termination than digoxin (HR=5.4; P =0.05) or flecainide (HR=7.4; P =0.03). If incessant AF/SVT persisted to day 5 (n=45), median ventricular rates declined more with flecainide (−22%) and digoxin (−13%) than with sotalol (−5%; P &lt;0.001). Flecainide (HR=2.1; P =0.02) and digoxin (HR=2.9; P =0.01) were also associated with a higher rate of conversion of fetal SVT to a normal rhythm over time. No serious drug-related adverse events were observed, but arrhythmia-related mortality was 5%. Conclusion— Flecainide and digoxin were superior to sotalol in converting SVT to a normal rhythm and in slowing both AF and SVT to better-tolerated ventricular rates and therefore might be considered first to treat significant fetal tachyarrhythmia.
Remarks on Battey's Operation
Authors: J. M. Sims
Journal: BMJ (1877)

Considering this, and considering that as yet we have no evidence, pro or contra, of organisms in relation to cholera, it would be certainly better, for the scientific discussion of the oetiological question relating to this disease, to dismiss germs for the present from consideration than to allow them to obscure the facts, or to confuse or bias our judgment as to their meaning.In point of fact, both of the opposing views have actually been so embodied.In most people's minds, the "germ-theory", as it is loosely called, of cholera is identified with contagionist views ; but, in the very philosophical work of Professor Nageli of Munich, just published,* you will find a much more maturely worked out theory of contagiuim vivutm, which is in accordance with Indian as well as with European experience.
Selection on the protein-coding genes of the TBE1 family of transposable elements in the ciliates Oxytricha fallax and O. trifallax
Authors: D. J. Witherspoon, T. G. Doak, K. R. Williams, A. Seegmiller, J. Seger, G. Herrick
Journal: Molecular Biology and Evolution (1997)

TBE1s are "cut-and-paste" transposable elements found in high copy number in the germline genomes of the ciliates Oxytricha fallax and O. trifallax. TBE1 "family" sequence (sequence of mixed polymerase chain reaction products generated using primers that match roughly half the TBE1s in host whole-cell DNA) was obtained from both host species. Although family sequence autoradiograms represent thousands of different elements, they are as legible as those representing corresponding sequences of a single TBE1, implying that ideal polymorphisms are rare within the genes examined. Nucleotide polymorphisms among TBE1s (indicated by ambiguities in family sequence) are far more common at third than at first or second positions of codons of genes, implying that selection has conserved the amino acid sequences of these genes in the majority of TBE1s. Portions of the transposase gene and another TBE1 gene have been sequenced from 10 individual TBE1s. None of these portions is interrupted by stop codons or frameshifts, and, for both genes, pairwise comparisons of these sequences show that nonsynonymous differences are significantly less common than synonymous differences, again implicating conservative selection Phylogenetic analysis shows that multiple divergent lineages of TBE1s have evolved under this selection within O. fallax. All these results are unexpected for cut-and-paste transposons in eukaryotic hosts: since transposase encoded by intact elements presumably acts in trans, it can duplicate mutant copies (those that do not encode functional transposase) found in the same genome, and thus no selection is expected to maintain the transposase gene. The selection demonstrated here could act at transposition (if functional TBE1s are preferentially transposed) or at the level of the host (if the host's fitness depends on functional TBE1 genes). TBE1-encoded proteins might be responsible for the precise excision of TBE1s that occurs during development of the host somatic nucleus; selection on hosts for uninterrupted somatic genes would then translate into selection for TBE1 protein-coding competence. We suggest a method for distinguishing between these two classes of explanations by finding and analyzing divergent alleles of ancestral transposable element insertions.
Mutation of the phospholipase C-γ1–binding site of LAT affects both positive and negative thymocyte selection
Authors: Connie L. Sommers, Jan Lee, Kevin L. Steiner, Jordan M. Gurson, Corinne L. DePersis, Dalal El-Khoury, Claudette L. Fuller, Elizabeth W. Shores, Paul E. Love, Lawrence E. Samelson
Journal: The Journal of Experimental Medicine (2005)

Linker for activation of T cells (LAT) is a scaffolding adaptor protein that is critical for T cell development and function. A mutation of LAT (Y136F) that disrupts phospholipase C-γ1 activation and subsequent calcium influx causes a partial block in T cell development and leads to a severe lymphoproliferative disease in homozygous knock-in mice. One possible contribution to the fatal disease of LAT Y136F knock-in mice could be from autoreactive T cells generated in these mice because of altered thymocyte selection. To examine the impact of the LAT Y136F mutation on thymocyte positive and negative selection, we bred this mutation onto the HY T cell receptor (TCR) transgenic, recombination activating gene-2 knockout background. Female mice with this genotype showed a severe defect in positive selection, whereas male mice exhibited a phenotype resembling positive selection (i.e., development and survival of CD8hi HY TCR-specific T cells) instead of negative selection. These results support the hypothesis that in non-TCR transgenic, LAT Y136F knock-in mice, altered thymocyte selection leads to the survival and proliferation of autoreactive T cells that would otherwise be negatively selected in the thymus.
Arris and Eale Lecture on ANATOMY, ORTHODOX AND HETERODOX, IN RELATION TO SURGERY
Authors: W. M. Eccles
Journal: BMJ (1930)

WVRAT was ol tlio(lox' in 1646 wI-heii lE(dward Arr1is founl1 ded lite lectureshil) was that the huio(ler of the office, whlich I llave thlc lionooir to-day to possess, should be.a, Reader of the, Miuscuflar Lecture."I leave it to vou tojudgeae exactly wi-liat was meant by this titl e for.by it 1 sliall (lolildoubtedly ble beterolodox n10w.My laterlpe(decessors Iin (ffice w-ere styled Masters in An.atomyiv, " anid ilieludedPercaiPoall Pott and Johni Hunter.
Longitudinal comparison of depression, coping, and turnover among NHS and private sector staff caring for people with dementia
Authors: M Margallo-Lana
Journal: BMJ (2001)

from the perspective of both the patient and the physician. 13Also, patients may undergo extensive investigation and medical treatment, which may not only be inappropriate but also hazardous. 14Iatrogenic factors such as inappropriate information, overinvestigation, and overtreatment are common in the management of these patients. 15 16 Avoidance of these factors forms the mainstay of most advice on management. 17We have shown that medically unexplained symptoms account for a considerable proportion of presentations in frequent attenders in secondary care and conclude that these patients should be considered a focus for attention.We thank all of the NHS trusts who agreed to participate in this study and in particular the medical records staff who assisted in retrieval of case notes.We also thank Dr R Hooper for providing statistical advice and helpful comments on the paper.
Phase 2 trial design in neuro-oncology revisited: a report from the RANO group
Authors: Evanthia Galanis, Wenting Wu, Timothy Cloughesy, Kathleen Lamborn, Bhupinder Mann, Patrick Y Wen, David A Reardon, Wolfgang Wick, David Macdonald, Terri S Armstrong, Michael Weller, Michael Vogelbaum, Howard Colman, Daniel J Sargent, Martin J van den Bent, Mark Gilbert, Susan Chang
Journal: The Lancet Oncology (2012)