tbuckley/cabot-search huggingface dataset:
Causes of 'natural' sudden death.
Authors: H. A. Fleming
Journal: BMJ (1989)

<h3>Objective</h3> It is purported that exercise-induced dehydration (EID), especially if ≥ 2% bodyweight, impairs endurance performance (EP). Field research shows that athletes can achieve outstanding EP while dehydrated &gt; 2% bodyweight. Using the meta-analytic procedure, this study compared the findings of laboratory-based studies that examined the impact of EID upon EP using either ecologically valid (EV) (time-trial exercise) or non-ecologically valid (NEV) (clamped-intensity exercise) exercise protocols. <h3>Methods</h3> EP outcomes were put on the same scale and represent % changes in power output between euhydrated and dehydrated exercise tests. Random-effects model meta-regressions and weighted mean effect summaries, mixed-effects model analogue to the ANOVAs and magnitude-based effect statistics were used to delineate treatment effects. <h3>Main results</h3> Fifteen research articles were included, producing 28 effect estimates, representing 122 subjects. Compared with euhydration, EID increased (0.09±2.60%, (p=0.9)) EP under time-trial exercise conditions, whereas it reduced it (1.91±1.53%, (p&lt;0.05)) with NEV exercise protocols. Only with NEV exercise protocols did EID ≥ 2% body weight impair EP (p=0.03). <h3>Conclusions</h3> Evidence indicates that (1) EID ≤ 4% bodyweight is very unlikely to impair EP under real-world exercise conditions (time-trial type exercise) and; (2) under situations of fixed-exercise intensity, which may have some relevance for military and occupational settings, EID ≥ 2% bodyweight is associated with a reduction in endurance capacity. The 2% bodyweight loss rule has been established from findings of studies using NEV exercise protocols and does not apply to out-of-doors exercise conditions. Athletes are therefore encouraged to drink according to thirst during exercise.
Glucose polymer supplementation of feeds for very low birthweight infants.
Authors: A Raffles, G Schiller, P Erhardt, M Silverman
Journal: BMJ (1983)

The feeds of 14 very low birthweight infants (birth weight less than 1500 g) were supplemented with a glucose polymer (Caloreen) at the rate of 6 g/kg body weight daily. Seven day periods of supplementation were alternated with seven day periods of normal feeding. Adding the glucose polymer significantly increased the rate of weight gain in these infants from 105 g/week to 140 g/week; growth rates in terms of length and head circumference were not affected. No adverse effects were noted. Glucose polymer is a useful energy supplement for very low birthweight infants.
The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes
Authors: David P. Steensma, Gordon W. Dewald, Terra L. Lasho, Heather L. Powell, Rebecca F. McClure, Ross L. Levine, D. Gary Gilliland, Ayalew Tefferi
Journal: Blood (2005)
The Artificial Kidney
Authors: John P. Merrill
Journal: New England Journal of Medicine (1952)

THE opening paragraph of the first published work on the artificial kidney reads as follows:There are numerous toxic states in which the eliminating organs of the body, more especially the kidneys, are incapable of removing from the body, at an adequate rate, the natural or un-natural substances whose accumulation is detrimental to life. In the hope of providing a substitute in such emergencies, which might tide over a dangerous crisis, as well as for the important information which it might be expected to provide, concerning the substances normally present in the blood, and also for the light that might . . .
THE RENAL LESIONS OF ELECTROLYTE IMBALANCE
Authors: J. Oliver, M. MacDowell, R. Whang, L. G. Welt
Journal: The Journal of Experimental Medicine (1966)

A dietary depletion of magnesium in rats leads to the production in the thin limb of Henle's loop of the nephrons of spherical microliths composed of a matrix of PAS-positive substances and calcium phosphate (3). These microliths grow by accretion to form intranephronic calculi. The classical pathological syndrome of clinical nephrolithiasis is thus reproduced within the nephron; to wit, the origin of the calculus at a certain level, local traumatic damage at the site of its origin, passage with the fluid flow down the urinary passages, lodgment of the calculus at some restricting point, obstruction of fluid flow and the usual consequent localized intrarenal "hydronephrotic" alterations of regressive atrophic cellular dysplasias within the nephron. To the classical description of the two forms of urinary lithiases occurring in the bladder and in the renal pelvis must therefore be added a third form, intranephronic calculosis. From the first origin of a microlith to its ultimate form as a calculus its organized structure is characterized by its matrix (PAS-positive materials) in which the periodic precipitation of crystalline mineral (Ca(++), PO(3) (---)) occurs in a pattern simulating Liesegang rings.
Selective killing of malignant B cells using T cells redirected against malignancy variant receptor
Authors: Chungyong Han, Sujung Sim, Kwang Hui Kim, Don Gil Lee, Ho Sik Oh, Sang Hyun Park, Sunhee Hwang, Won Young Kim, Sangeun Lee, Young Ho Kim, Beom Kyu Choi, Carl June, Byoung Se Kwon
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Advances in gene-transfer system and in-depth understanding of immune mechanism have made the immunotherapy a powerful tool for fighting against cancers. Recent studies demonstrated a therapeutic potential of T cells with chimeric antigen receptor (CAR) targeting CD19 in
The National Institute for Clinical Excellence (NICE)
Authors: A-T Rodgers
Journal: Annals of the Rheumatic Diseases (2002)

The National Institute for Clinical Excellence (NICE or the Institute) is part of the UK NHS. It provides guidance for the NHS and patients and their carers that aims to inform decisions about treatment and healthcare. Anne-Toni Rodgers, one of the directors of NICE and an executive lead for many NICE projects, provided an outline of the organisation and the Appraisal Process. In addition she summarised the Institute’s recent guidance on the use of etanercept and infliximab for the treatment of rheumatoid arthritis.

All healthcare workers want to give their patients the best possible care but they face two major problems.

As a result, unacceptable variations in the quality of care available for patients were seen in different parts of the country (so called “postcode” prescribing). The white papers The New NHS Modern and Dependable 1and NHS Wales’ Putting Patients Firs t,2 set out the government’s overall agenda for improving the quality of health care in the NHS in England and Wales. More detail …
Abstract 2652: Effect of selective serotonergic reuptake inhibitors on radiation therapy
Authors: Nicci P. Moran, Michelle A. Romano, Graham W. Warren
Journal: Cancer Research (2011)

Abstract Introduction: Selective serotonergic reuptake inhibitors (SSRIs) are well-established antidepressants commonly used in cancer patients. Studies suggest that SSRIs may play a role in increased cell death in cancer cells; however, the use of SSRIs as adjunctive agents to be used in combination with conventional cancer treatment is not well established. The purpose of this study was to evaluate the effect of SSRIs on cell survival in combination with radiation therapy (XRT). Methods: Human lung cancer lines (A-549 and H-460) and squamous oropharyngeal cancer cells (FaDu) were treated with several dose escalated SSRIs (fluoxetine, sertraline, paroxetine) alone or in combination with dose escalated XRT (0,2,4,6 Gy) to evaluate the cytotoxic effects of SSRIs using clonogenic survival assays. Western blot analysis was used to evaluate apoptosis (cleaved Caspase-3 and cleaved PARP) and autophagy (LC3-II) to assess potential mechanisms of the effects of SSRIs on XRT. Results: Fluoxetine, paroxetine, or sertraline alone had a cytotoxic effect on cancer cells in a concentration dependent manner. Sertraline and paroxetine at 2.5-5uM appeared to have an additive effect on XRT with severe cytotoxicity noted at higher concentrations. In contrast, fluoxetine appeared to have a sensitizing effect on cells at 1-10uM in a tumor cell specific manor. Western blot analysis demonstrated that fluoxetine administration decreased cleaved Caspase-3 and cleaved PARP expression at 24 or 48 hours. Evaluation of autophagy using LC3-II demonstrated no change with XRT; however, treatment with fluoxetine increased the expression of LC3-II at 24 and 48 hours in the presence or absence of XRT. Conclusions: Most SSRIs appear to have a cytotoxic effect alone or in combination with XRT. Fluoxetine appears to have a unique sensitizing effect on XRT in cancerous cells possibly through an increased induction of autophagy. Data supports further examination of fluoxetine as an adjunctive agent in combination with XRT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2652. doi:10.1158/1538-7445.AM2011-2652
Abstract P2-11-19: Expression of folate receptor alpha in ductal carcinoma in situ of the breast and comparison with that of invasive ductal carcinoma
Authors: Z Zhang, J Wang, D Tacha, P Li, R Bremer, K Skinner, DG Hicks, H Bu, P Tang
Journal: Cancer Research (2013)

Abstract Background: We have previously shown that the expression of Folate receptor alpha (FRA) is associated with high grade ER-/PR- or triple negative (TN) invasive ductal carcinoma of the breast. The aim of the current study is to investigate the expression pattern of FRA in a cohort of ductal carcinoma in situ (DCIS), analyze its relationship with different clinicopathological features and expression of several key biomarkers, and compare these findings to our previous data on invasive ductal carcinoma (IDC). Methods: Ninety-eight cases of DCIS of the breast diagnosed between 1997 and 2008 in our institution were identified, reviewed and 6 blocks of tissue microassays (TMA) were constructed. The association between the expression of FRA (≥10% designed as positive expression) and the clinicopathologic features, the expression of ER, PR, HER2 and Ki-67, and the clinical outcome were evaluated, and these results were compared to those from IDC (399/430 cases with informative data). Results: Among the 98 cases of DCIS in TMA, 88 cases were informative. The expression rate of FRA was 21% for DCIS, less than the 29% seen in IDC. Expression of FRA was associated with high nuclear grades (42%), though less frequently than with IDC (52%). FRA expression was also associated with ER negativity (46%), PR negativity (33%) and high Ki-67 expression (50%) in DCIS, although significantly less than in IDC (75%, 63%, and 56%, respectively for negative ER and PR, and high Ki-67). Also, only 50% of ER/PR negative, TN and basal-like DCIS expressed FRA, significantly lower than that of IDC (74%, 80% and 80%, respectively). Due to the limited cases of DCIS, we did not demonstrate a significant difference in disease-free survival between FRA positive and negative tumors (p-value = 0.1792), although we did observe that IDC with FRA expression was significantly associated with a worse disease-free survival (p-value = 0.04). Comparison between FRA expression between DCIS and IDC FRA≥10% in DCISFRA≥10% in IDCp-value 88 cases399 cases Nuclear 342%52%0.0185ER negative46%75%0.0442PR negative33%63%0.0214HER2 3+31%37%0.7003ER-/PR-50%74%0.0973Triple Negative50%80%0.1622Basal-Like50%80%0.1739 Conclusion: Our data demonstrates that FRA expression is associated with high nuclear grade, ER/PR negative and TN DCIS, though at a significantly lower rate than was observed in IDC, suggesting a possible role for this receptor in early breast carcinogenesis. There are differences in the rates of FRA expression between DCIS and IDC, suggesting that FRA may be one of the key molecules involved in progression of DCIS to IDC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-19.
Abstract IA11: MicroRNAs in oncogenic and tumor suppressor signaling pathways
Authors: Joshua T. Mendell
Journal: Cancer Research (2013)

Abstract MicroRNA (miRNA) gain- and loss-of-function can potently influence cellular behavior in normal physiologic states and in diseases such as cancer. The regulation of miRNA expression and activity by cellular signaling cascades can therefore result in dramatic phenotypic outputs. We previously demonstrated extensive control of miRNA expression by well-characterized oncogenic and tumor suppressor networks including the Myc, Kras, and p53 pathways. We are now employing novel mouse models with gain and loss of miRNA function to investigate the physiologic functions of the miRNAs embedded within these signaling pathways and the pathologic consequences when their functions are disrupted. Insights gained from these studies are revealing unanticipated roles for miRNAs in vivo and are informing our understanding of how dysregulated miRNA activity contributes to tumorigenesis. I will present our latest findings related to the regulation and function of mammalian miRNAs in normal physiology and in cancer and how these findings may be exploited for the development of novel therapeutic approaches. Citation Format: Joshua T. Mendell. MicroRNAs in oncogenic and tumor suppressor signaling pathways. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr IA11.
The persistent elimination of B cells responding to blood group A carbohydrates by synthetic group A carbohydrates and B-1 cell differentiation blockade: novel concept in preventing antibody-mediated rejection in ABO-incompatible transplantation
Authors: Toshimitsu Irei, Hideki Ohdan, Wendy Zhou, Kohei Ishiyama, Yuka Tanaka, Kentaro Ide, Toshimasa Asahara
Journal: Blood (2007)
3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone
Authors: Thomas S Scanlan, Katherine L Suchland, Matthew E Hart, Grazia Chiellini, Yong Huang, Paul J Kruzich, Sabina Frascarelli, Dane A Crossley, James R Bunzow, Simonetta Ronca-Testoni, Emil T Lin, Daniel Hatton, Riccardo Zucchi, David K Grandy
Journal: Nature Medicine (2004)
Hypoxia, vascular smooth muscles and endothelium
Authors: Calvin K. Chan, Paul M. Vanhoutte
Journal: Acta Pharmaceutica Sinica B (2013)

Hypoxia, or the lack of oxygen, has multiple impacts on the vascular system. The major molecular sensors for hypoxia at the cellular level are hypoxia inducible factor and heme oxygenase. Hypoxia also acts on the vasculature directly conveying its damaging effects through disruption of the control of vascular tone, particularly in the coronary circulation, enhancement of inflammatory responses and activation of coagulation pathways. These effects could be particularly detrimental under pathological conditions such as obstructive sleep apnea and other breathing disorders.
Safety and efficacy of a new non-foreshortening nitinol stent in malignant gastric outlet obstruction (DUONITI study): a prospective, multicenter study
Authors: J. van Hooft, M. van Montfoort, S. Jeurnink, M. Bruno, M. Dijkgraaf, P. Siersema, P. Fockens
Journal: Endoscopy (2011)

Background and study aims: Gastric outlet obstruction (GOO) is a late complication of advanced gastric, periampullary, and duodenal malignancies. Palliation of obstruction is the primary aim of treatment in these patients. Self-expandable metal stents have emerged as a promising treatment option. Our aim was to investigate the safety and efficacy of a new non-foreshortening nitinol duodenal stent.
AN ELECTRON MICROSCOPE STUDY OF RECEPTOR SITES ON RAT MAST CELLS FOR HUMAN IMMUNOGLOBULIN E
Authors: R. PONTEFRACT, L. PERELMUTTER
Journal: Allergy (1976)

Previous studies using immunofluorescence and autoradiography demonstrated the presence of specific immunoglobulin E (IgE) receptors on rat mast cells (RMC). This finding was confirmed by the use of transmission electron microscopy (TEM) combined with X-ray microanalysis (XMA) employing ferritin labelled antisera XMA was used to detect ferritin as Fe in the target cells. On examination by TEM and XMA, 25 per cent of RMC showed a dense area of Fe deposits on the surface of the cells. No Fe could be detected on neutrophils or eosinophils or in the control cell preparations without human IgE. The Fe was concentrated in well-defined areas of the treated mast cells and this distinct concentration of receptor sites was similar to that observed by other investigators who have termed this phenomenon, "cap" formation.
Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf/p53 pathway lesions but not p16Ink4a loss
Authors: Michael T. Debies, Shelley A. Gestl, Jessica L. Mathers, Oliver R. Mikse, Travis L. Leonard, Susan E. Moody, Lewis A. Chodosh, Robert D. Cardiff, Edward J. Gunther
Journal: Journal of Clinical Investigation (2008)

Breast cancers frequently progress or relapse during targeted therapy, but the molecular mechanisms that enable escape remain poorly understood. We elucidated genetic determinants underlying tumor escape in a transgenic mouse model of Wnt pathway–driven breast cancer, wherein targeted therapy is simulated by abrogating doxycycline-dependent Wnt1 transgene expression within established tumors. In mice with intact tumor suppressor pathways, tumors typically circumvented doxycycline withdrawal by reactivating Wnt signaling, either via aberrant (doxycycline-independent) Wnt1 transgene expression or via acquired somatic mutations in the gene encoding β-catenin. Germline introduction of mutant tumor suppressor alleles into the model altered the timing and mode of tumor escape. Relapses occurring in the context of null Ink4a/Arf alleles (disrupting both the p16Ink4a and p19Arf tumor suppressors) arose quickly and rarely reactivated the Wnt pathway. In addition, Ink4a/Arf-deficient relapses resembled p53-deficient relapses in that both displayed morphologic and molecular hallmarks of an epithelial-to-mesenchymal transition (EMT). Notably, Ink4a/Arf deficiency promoted relapse in the absence of gross genomic instability. Moreover, Ink4a/Arf-encoded proteins differed in their capacity to suppress oncogene independence. Isolated p19Arf deficiency mirrored p53 deficiency in that both promoted rapid, EMT-associated mammary tumor escape, whereas isolated p16Ink4a deficiency failed to accelerate relapse. Thus, p19Arf/p53 pathway lesions may promote mammary cancer relapse even when inhibition of a targeted oncogenic signaling pathway remains in force.
OBSERVATIONS ON EXPERIMENTAL TYPHOID INFECTION OF THE GALL BLADDER IN THE RABBIT
Authors: Henry J. Nichols
Journal: The Journal of Experimental Medicine (1914)

1. Besredka's living sensitized vaccine, given intravenously, does not produce a typhoid lesion of the gall bladder in the rabbit. 2. The first transplant of this vaccine is capable of producing this lesion. Hence this vaccine is not entirely safe to handle. 3. Regular infections of the gall bladder have not been produced by carrying a known pathogenic strain on rabbit blood agar, by successive passage through animals, or by the use of freshly isolated strains. 4. No evidence could be demonstrated in the rabbit of the immunity produced in man by vaccination with a whole killed vaccine. 5. Vaccine treatment did not cure the gall bladder lesion. 6. With the present methods of producing infections in the chimpanzee and the rabbit, neither of these animals is suitable for deciding the problems of the immunization of man by vaccines. These problems must be settled, as some of them already have been settled, by actual experience with large numbers of men kept under close observation.
FOREIGN BODY IN THE AIR PASSAGES
Authors: H. Tilley
Journal: BMJ (1909)

Adapter proteins such as Grb2 play a central role in the formation of signaling complexes through their association with multiple protein binding partners. These interactions are mediated by specialized domains such as the well-characterized Src homology SH2 and SH3 motifs. Using yeast three-hybrid technology, we have identified a novel adapter protein, expressed predominantly in T lymphocytes, that associates with the activated form of the costimulatory receptor, CD28. The protein is a member of the Grb2 family of adapter proteins and contains an SH3-SH2-SH3 domain structure. A unique glutamine/proline-rich domain (insert domain) of unknown function is situated between the SH2 and N-terminal SH3 domains. We term this protein GRID for Grb2-related protein with insert domain. GRID coimmunoprecipitates with CD28 from Jurkat cell lysates following activation of CD28. Using mutants of CD28 and GRID, we demonstrate that interaction between the proteins is dependent on phosphorylation of CD28 at tyrosine 173 and integrity of the GRID SH2 domain, although there are also subsidiary stabilizing contacts between the PXXP motifs of CD28 and the GRID C-terminal SH3 domain. In addition to CD28, GRID interacts with a number of other T cell signaling proteins, including SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), p62<sup><i>dok</i></sup>, and RACK-1 (receptor for activated protein kinase C-1). These findings suggest that GRID functions as an adapter protein in the CD28-mediated costimulatory pathway in T cells.
STUDIES ON ACUTE NEPHRITIS
Authors: K. Petren
Journal: BMJ (1919)

1919-ACUTE N-PHRITI8.M-.D c&TJounzas Hospital with malaria.Bilateral enlargement, some discom- fort in throat, but no dysphagia or dyspnioea.Pulse 1207130.Spleen not enlarged.Progress as in Case V.CASE VII.Cpl. J., aged 24.Two previousg attacks.Benign tertian parasites.Constriction in throat and dyspnoea noticed after second attack.Had slight bilateral enlargement of thyroid, accompanied by marked tachycardia-120 and slight tremor.
David Howard Casson
Authors: M. Dalzell
Journal: BMJ (2010)

David Howard Casson (“Dave”) was born in Didsbury in Manchester, son of a general practitioner. He attended Manchester Grammar School and St Edmund Hall, Oxford, before postgraduate studies at St Bartholomew’s Hospital, London. Dave travelled widely from London to Bournemouth, Bath, and more, including Pakistan and Australia, and was appointed consultant paediatric gastroenterologist at Alder Hey in 2000.

It was in Dave’s nature to always …
Physicians can help in reducing child abuse
Authors: William A. Check
Journal: JAMA (1980)

Between 1974 and 1977,  US Department of Health and Human Services (formerly  US Department of Health, Education, and Welfare), through  National Center for Health Services Research, sponsored a study of treatment programs for parents who abused their children. In all, 1,724 abusing parents were treated at 11 demonstration centers.  In  February 1980 issue of Pediatrics , Anne Harris Cohn, DPH, summarizes  results of  study.  Overall, says Cohn, the treatment programs... were not particularly successful in helping abusive parents and thus in protecting  child. For instance, 30% of  children were reabused while their parents were in treatment. And only 42% of  parents were less likely to reabuse their children after treatment. This, despite  fact that the programs studied... had access to special resources and expertise.  None of  parents' characteristics was predictive of who would benefit from treatment. However, one treatment factor
BTA &lt;i&gt;stat&lt;/i&gt; and BTA TRAK: A Comparative Evaluation of Urine Testing for the Diagnosis of Transitional Cell Carcinoma of the Bladder
Authors: Jacques Irani, Fran&ccedil;ois Desgrandchamps, Christine Millet, Marie-Elizabeth Toubert, Didier Bon, Jacques Aubert, Alain LeDuc
Journal: European Urology (1999)