tbuckley/cabot-search huggingface dataset:
Cystamine potently suppresses in vitro HIV replication in acutely and chronically infected human cells.
Authors: A Bergamini, M Capozzi, L Ghibelli, L Dini, A Salanitro, G Milanese, T Wagner, S Beninati, C D Pesce, C Amici
Journal: Journal of Clinical Investigation (1994)

We have investigated the effects of cystamine on the replication of human immunodeficiency virus (HIV) in human lymphocytes and macrophages, the natural targets of HIV in vivo. Treatment of chronically infected macrophages with cystamine, at a concentration (500 microM) that did not show any cytotoxic or cytostatic effects, strongly decreased (> 80%) HIV-p24 antigen production and completely abolished the production of infectious viral particles. Cystamine does not affect viral transcription, translation or protein processing; indeed, all HIV proteins are present in a pattern similar to that of nontreated cells. Instead, cystamine interferes with the orderly assembly of HIV virions, as shown by electron microscopy analysis, that reveals only defective viral particles in treated cells. Moreover, suppression of HIV replication, due to the inhibition of proviral DNA formation was observed in acutely infected lymphocytes and macrophages pretreated with cystamine. These results show that cystamine potently suppresses HIV replication in human cells by contemporaneously blocking at least two independent steps of the viral life cycle, without affecting cell viability, suggesting that this compound may represent a new possibility towards the treatment of HIV-1 infection.
Confidentiality and Electronic Medical Records
Authors: David M. Rind
Journal: Annals of Internal Medicine (1998)

Letters15 March 1998Confidentiality and Electronic Medical RecordsDavid M. Rind, MD, Peter Szolovits, PhD, and Isaac S. Kohane, MD, PhDDavid M. Rind, MDBeth Israel Deaconess Medical Center; Boston, MA 02115Massachusetts Institute of Technology; Cambridge, MA 02139Children's Hospital; Boston, MA 02115Search for more papers by this author, Peter Szolovits, PhDBeth Israel Deaconess Medical Center; Boston, MA 02115Massachusetts Institute of Technology; Cambridge, MA 02139Children's Hospital; Boston, MA 02115Search for more papers by this author, and Isaac S. Kohane, MD, PhDBeth Israel Deaconess Medical Center; Boston, MA 02115Massachusetts Institute of Technology; Cambridge, MA 02139Children's Hospital; Boston, MA 02115Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-6-199803150-00033 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Mr. Roberts, Ms. Decter, and Dr. Nagel raise several considerations that underlie the balance we attempted to strike between access and confidentiality in our proposal on transmitting medical records over the World Wide Web.We favor any workable methods to inform patients that they may, ahead of time, restrict any electronic release of records. Such methods might include publicity about the planned institution of the World Wide Web Electronic Medical Record System (W3-EMRS) and fliers available at participating institutions. To our knowledge, institutions do not currently have procedures to allow patients to restrict emergency release of paper records ... Author, Article, and Disclosure InformationAuthors: David M. Rind, MD; Peter Szolovits, PhD; Isaac S. Kohane, MD, PhDAffiliations: Beth Israel Deaconess Medical Center; Boston, MA 02115Massachusetts Institute of Technology; Cambridge, MA 02139Children's Hospital; Boston, MA 02115 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byShared expectations for protection of identifiable health care informationInternet-Based Monitoring and Benchmarking in Ambulatory Surgery Centers 15 March 1998Volume 128, Issue 6Page: 510-511KeywordsAllergy and immunologyElectrode recordingElectronic medical recordsFallsInformation technologyInternetPatients ePublished: 15 August 2000 Issue Published: 15 March 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Forced expiratory indices in normal Libyan men.
Authors: M H Shamssain
Journal: Thorax (1988)

Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory ratio in the first second (FEV1% VC), forced expiratory flow between 200 and 1200 ml (FEF200-1200), and forced mid expiratory flow between 25% and 75% of FVC (FMF) were measured in 275 Libyan men ranging from 20 to 60 years. All values were lower with increasing age and, apart from FEV1% VC, were positively correlated with standing height. This study can be used as a source of reference for Libyan men.
Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch.
Authors: K G Cornish, W L Joyner, J P Gilmore
Journal: Circulation Research (1979)

Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II.
Reduced Notch Signaling Leads to Renal Cysts and Papillary Microadenomas
Authors: Kameswaran Surendran, Meron Selassie, Helen Liapis, Hannah Krigman, Raphael Kopan
Journal: Journal of the American Society of Nephrology (2010)

The formation of proximal nephron segments requires canonical Notch2 signaling, but other functions of Notch signaling during renal development are incompletely understood. Here, we report that proximal tubules forming with reduced Notch signaling, resulting from delayed conditional inactivation of Notch1 and/or Notch2, are prone to cyst formation and tubular epithelial stratification. Conditional inactivation of the DNA binding factor RBP-J, which mediates Notch signaling, also resulted in multiple congenital cysts arising from the proximal tubule. Moreover, a few stratified foci/microadenomas containing hyperproliferative cells, resembling precursors of papillary renal cell carcinoma, formed in these proximal tubules. Epithelial stratification correlated neither with reduced expression of the transcriptional regulator of ciliary proteins TCF2/HNF1β nor with loss of apical-basal polarity. Instead, Notch signaling helped to restrict the orientation of epithelial mitotic spindles to a plane parallel to the basement membrane during nephron elongation. In the absence of Notch, random spindle orientation may explain the epithelial stratification and cyst formation. Furthermore, post hoc analysis of human class 1 papillary renal cell carcinoma revealed reduced Notch activity in these tumors, resulting from abundant expression of a potent inhibitor of canonical Notch signaling, KyoT3/FHL1B. In summary, these data suggest that canonical Notch signaling maintains the alignment of cell division in the proximal tubules during nephrogenesis and that perturbations in Notch signaling may lead to cystic renal disease and tumorigenesis.
Hypoxia-induced autophagy in endothelial cells: a double-edged sword in the progression of infantile haemangioma?
Authors: Gang Chen, Wei Zhang, Yin-Ping Li, Jian-Gang Ren, Ning Xu, Hui Liu, Feng-Qin Wang, Zhi-Jun Sun, Jun Jia, Yi-Fang Zhao
Journal: Cardiovascular Research (2013)

The aim of this study was to investigate the precise role of hypoxia-induced autophagy in endothelial cells, and whether it contributes to the distinctive progression of infantile haemangioma (IH).The endothelial cells (EOMA and HUVECs) were cultured under hypoxic conditions for indicated times (0-72 h). The results showed that short exposure of the endothelial cells to hypoxia resulted in increased cell survival and proliferation, accompanied by occurrence of autophagy. Prolonged hypoxia-induced autophagy, correlating with increased cell death, was also detected afterwards. Correspondingly, autophagy inhibition prevented the enhanced cell survival and proliferation capacity, advanced the occurrence of cell-death in early hypoxic stage, and meanwhile attenuated the ability of prolonged hypoxia in cell-death induction. Moreover, our data demonstrated that the functional transformation of hypoxia-induced autophagy, pro-survival to pro-death, was rigorously regulated by the switch between hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) pathways. Importantly, we also revealed the activation levels of HIF-1α and mTOR, as well as the autophagy status during the progression of IH.This study unmasks the functional switch between HIF-1α and mTOR in regulating hypoxia-induced autophagy in endothelial cells and, more importantly, indicates its potential role in the progression of IH.
Overconfidence in warfare
Authors: M. Potts
Journal: Journal of the Royal Society of Medicine (2007)

By couching the discussion of Blair and Bush in terms of hubris and nemesis, Lord Owen 1 has avoided the pitfall of diagnosis from afar while still highlighting serious problems with the two world leaders (JRSM November 2006).He does dip his toe into psychodynamics citing Freud and Justin Frank, but, by and large, he sticks to discussing behaviour and its relation to hubris and power.As a politician, Lord Owen is qualified to discuss the political leaders he has encountered.As a physician, should he be making medical judgments on political leaders?Simon Wessely has questions about this and about whether or not psychiatrists should venture beyond the consulting room. 2 Should psychiatrists limit their judgments to patients they have examined?The American Psychiatric Association says 'yes' and Dr Wessely cites data to support that view.But the question remains, can psychiatrists and neuroscientists, with the help of philosophers, provide useful insights that contribute to the understanding of leaders and their followers?I believe that we should try.We should bring whatever scientific data there may be to counter ideology, blind faith and the intoxicating effects of power.It is true hubris often comes with power.Even though we do not have a psychiatric diagnosis for hubris, it is a psychological entity and as such should potentially be understood by science, as are other psychological phenomena.We do not diagnose those that we have not personally examined and we cannot diagnose an entire population, but perhaps we can bring clinical and scientific insights to help understand destructive behaviour As scientists and clinicians, we too must guard against hubris.Hopefully our colleagues will help us with that.JRMS should be applauded for exploring the issue.
Larval Therapy: A Novel Treatment in Eliminating Methicillin-Resistant <i>Staphylococcus aureus</i> From Diabetic Foot Ulcers
Authors: Frank L. Bowling, Eleanna V. Salgami, Andrew J.M. Boulton
Journal: Diabetes Care (2007)

Overuse of antibiotics and the selection of broad- rather than narrow-spectrum agents have contributed to the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization in diabetic foot wounds. Consequently, MRSA is now an endemic in both the community and hospital environments (1,2). We previously highlighted the problem (3) of MRSA colonization in our diabetic foot clinic (40% of S. aureus isolates were MRSA). A follow-up study (4) demonstrated that the number of foot wounds from which MRSA was isolated doubled in a 3-year period. Although terms such as critical colonization are not clearly defined, the risk of MRSA infection and bacteremia in patients with colonized ulcers is recognized (5,6). Furthermore, there is evidence (4) that MRSA colonization of chronic ulcers is associated with delayed healing times. Strategies to eliminate MRSA from colonized wounds are therefore essential and should include the use of simple, low-cost, effective treatments.

Larval therapy is suggested (7) to successfully remove sloughy necrotic tissue from ulcers and to facilitate healing. We hypothesized that larval therapy would eradicate MRSA colonization from diabetic foot ulcers. Here, we report the results of our preliminary …
An Unsupervised Approach to Identify Molecular Phenotypic Components Influencing Breast Cancer Features
Authors: Florin M. Selaru, Jing Yin, Andreea Olaru, Yuriko Mori, Yan Xu, Steven H. Epstein, Fumiaki Sato, Elena Deacu, Suna Wang, Anca Sterian, Amy Fulton, John M. Abraham, David Shibata, Claudia Baquet, Sanford A. Stass, Stephen J. Meltzer
Journal: Cancer Research (2004)

To discover a biological basis for clinical subgroupings within breast cancers, we applied principal components (PCs) analysis to cDNA microarray data from 36 breast cancers. We correlated the resulting PCs with clinical features. The 35 PCs discovered were ranked in order of their impact on gene expression patterns. Interestingly, PC 7 identified a unique subgroup consisting of estrogen receptor (ER); (+) African-American patients. This group exhibited global molecular phenotypes significantly different from both ER (-) African-American women and ER (+) or ER (-) Caucasian women (P < 0.001). Additional significant PCs included PC 4, correlating with lymph node metastasis (P = 0.04), and PC 10, with tumor stage (stage 2 versus stage 3; P = 0.007). These results provide a molecular phenotypic basis for the existence of a biologically unique subgroup comprising ER (+) breast cancers from African-American patients. Moreover, these findings illustrate the potential of PCs analysis to detect molecular phenotypic bases for relevant clinical or biological features of human tumors in general.
Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women
Authors: Rowan T. Chlebowski, Lewis H. Kuller, Ross L. Prentice, Marcia L. Stefanick, JoAnn E. Manson, Margery Gass, Aaron K. Aragaki, Judith K. Ockene, Dorothy S. Lane, Gloria E. Sarto, Aleksandar Rajkovic, Robert Schenken, Susan L. Hendrix, Peter M. Ravdin, Thomas E. Rohan, Shagufta Yasmeen, Garnet Anderson
Journal: New England Journal of Medicine (2009)

Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.
Asymmetrical Dimethylarginine Predicts Progression to Dialysis and Death in Patients with Chronic Kidney Disease
Authors: Pietro Ravani, Giovanni Tripepi, Fabio Malberti, Sophie Testa, Francesca Mallamaci, Carmine Zoccali
Journal: Journal of the American Society of Nephrology (2005)

High plasma asymmetrical dimethylarginine (ADMA) signals endothelial dysfunction and atherosclerosis in the general population and predicts mortality in ESRD. The relationship among plasma levels of ADMA, renal function, and the risk for progression to ESRD (halving GFR or dialysis start) and death in an incident cohort of 131 patients with chronic kidney disease was investigated. Cox's competing risk regression was used to model double-failure times (progression to ESRD and death) as a function of ADMA. Covariates that were considered for adjustment included clinical characteristics, baseline GFR (Modification of Diet in Renal Disease equation 7 formula), proteinuria, traditional cardiovascular risk factors, serum C-reactive protein, homocysteine, and concomitant therapies. Mean age at enrollment was 71 +/- 11 yr, and 24% of patients had diabetes. Baseline GFR ranged from 8 to 77 ml/min per 1.73 m2 (average 31 +/- 15 ml/min per 1.73 m2). ADMA was inversely related to GFR, ranking as the third predicting factor (partial r = -0.22, P = 0.01), after hemoglobin and urinary protein, in a general linear model that included multiple correlates of GFR. After a mean follow-up of 27 mo (range 3.4 to 36), 29 patients progressed to ESRD and 31 died. ADMA (hazard ratio per 0.1 muM/L 1.203; 95% confidence interval 1.071 to 1.350) predicted event occurrence independent of other potential confounders, including GFR, proteinuria, hemoglobin, and homocysteine. In patients with mild to advanced chronic kidney disease, plasma ADMA is inversely related to GFR and represents a strong and independent risk marker for progression to ESRD and mortality. These novel findings further expand the implications of previous observations in ESRD patients and generate hypotheses on the role of ADMA in progressive chronic nephropathies.
Drug assessment in the Ebola virus disease epidemic in west Africa
Authors: Yazdan Yazdanpanah, Peter Horby, Johan van Griensven, France Mentre, Vinh-Kim Nguyen, Jean Marie Denis Malvy, Jake Dunning, Daouda Sissoko, Jean-Francois Delfraissy, Yves Levy
Journal: The Lancet Infectious Diseases (2015)
Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor–Initiating Cells
Authors: Chitra Venugopal, Robin Hallett, Parvez Vora, Branavan Manoranjan, Sujeivan Mahendram, Maleeha A. Qazi, Nicole McFarlane, Minomi Subapanditha, Sara M. Nolte, Mohini Singh, David Bakhshinyan, Neha Garg, Thusyanth Vijayakumar, Boleslaw Lach, John P. Provias, Kesava Reddy, Naresh K. Murty, Bradley W. Doble, Mickie Bhatia, John A. Hassell, Sheila K. Singh
Journal: Clinical Cancer Research (2015)

Clonal evolution of cancer may be regulated by determinants of stemness, specifically self-renewal, and current therapies have not considered how genetic perturbations or properties of stemness affect such functional processes. Glioblastoma-initiating cells (GICs), identified by expression of the cell surface marker CD133, are shown to be chemoradioresistant. In the current study, we sought to elucidate the functional role of CD133 in self-renewal and identify compounds that can specifically target this CD133(+) treatment-refractory population.Using gain/loss-of-function studies for CD133 we assessed the in vitro self-renewal and in vivo tumor formation capabilities of patient-derived glioblastoma cells. We generated a CD133 signature combined with an in silico screen to find compounds that target GICs. Self-renewal and proliferation assays on CD133-sorted samples were performed to identify the preferential action of hit compounds. In vivo efficacy of the lead compound pyrvinium was assessed in intracranial GIC xenografts and survival studies. Lastly, microarray analysis was performed on pyrvinium-treated GICs to discover core signaling events involved.We discovered pyrvinium, a small-molecule inhibitor of GIC self-renewal in vitro and in vivo, in part through inhibition of Wnt/β-catenin signaling and other essential stem cell regulatory pathways. We provide a therapeutically tractable strategy to target self-renewing, chemoradioresistant, and functionally important CD133(+) stem cells that drive glioblastoma relapse and mortality.Our study provides an integrated approach for the eradication of clonal populations responsible for cancer progression, and may apply to other aggressive and heterogeneous cancers.
Risk of adenocarcinoma in Barrett's oesophagus: population based study
Authors: Liam Murray, Peter Watson, Brian Johnston, James Sloan, Inder Mohan Lal Mainie, Anna Gavin
Journal: BMJ (2003)

hospital intubation without drugs was hopeless, 3 but we found that 8% of patients survived.The number was small, with the lower limit of the confidence interval of 0.2% just equal to the mean survival reported by the helicopter service.Anaesthesia and intubation can be complicated by head and facial injuries, cervical fractures, risk of oesophageal intubation, aspiration, circulatory deterioration, and increased intracerebral pressure.The environment out of hospital is different from in hospital and support and resources are limited.We question whether anaesthesia and intubation of trauma patients can be mastered and routine be maintained by ambulance personnel.
A clinician's guide to drug‐drug interactions with direct‐acting antiviral agents for the treatment of hepatitis C viral infection
Authors: Travis B. Dick, Lance S. Lindberg, Debra D. Ramirez, Michael R. Charlton
Journal: Hepatology (2015)

The US Food and Drug Administration has recently approved a number of new direct‐acting antiviral agents for the treatment of chronic hepatitis C virus that have significantly increased the likelihood of a virological cure. These agents are highly effective but present a substantial risk for a host of clinically relevant drug‐drug interactions. These interactions must be considered both when starting and stopping any medication, including over‐the‐counter medications and herbal supplements. These drug‐drug interactions can increase the risk of toxicity or decrease the likelihood of treatment response. Knowledge of these interactions is paramount in optimizing the success of antiviral therapy. Conclusion: In this review we summarize the available data regarding drug‐drug interactions for direct‐acting antiviral agents, the interactions being the most clinically relevant that are currently known; this review is intended to serve as a clinician's guide to understanding and managing these complex interactions . (H epatology 2016;63:634–643)
Comparability of shuttle walk test with 6-minutes walk test in pulmonary diseases with emphasis on pulmonary arterial hypertension
Authors: Barbara Salobir, Metka Medle, Marija Spelic, Marjeta Tercelj
Journal: European Respiratory Journal (2013)

Introduction. Exercise testing is useful to assess prognosis and response to treatment, especially in pulmonary arterial hypertension (PAH). Although 6-minute walk test (6MWT) is the test of choice, it might be harmful due to possible syncope and deterioration of right heart function in “over-motivated” young patients (already occurred in two our young PAH patients).   Aims and Objectives. To compare 6MWT with shuttle walk test (SWT), which might be safer since it is regulated and has to be stopped not only due to symptoms but also when sub-maximal heart rate or maximal distance (590m) is attained.   Methods. SWT and 6MWT were performed on consecutive days in 65patients with pulmonary diseases, 20 of them had PAH (3idiopathic, 11chronic thromboembolic, 3associated with connective tissue disease, 1with histiocytosis, 1with severe hypothyreosis, 1undetermined) and in 5healthy controls.   Results. SWT strongly correlated with 6MWT(r=0.81, p   Conclusions. According to excellent correlation between both tests, SWT might be option for assessing exercise capacity in young “over-motivated” patients with PAH in whom 6-MWT might be harmful due to exercise overload, what has to be proved.