tbuckley/cabot-search huggingface dataset:
Activation of Nuclear Factor-κB Contributes to Induction of Death Receptors and Apoptosis by the Synthetic Retinoid CD437 in DU145 Human Prostate Cancer Cells
Authors: Fengshuo Jin, Xiangguo Liu, Zhongmei Zhou, Ping Yue, Reuben Lotan, Fadlo R. Khuri, Leland W.K. Chung, Shi-Yong Sun
Journal: Cancer Research (2005)

Abstract Activation of the transcription factor, nuclear factor-κB (NF-κB), results in up-regulation of not only antiapoptotic genes but also proapoptotic genes, including death receptor 4 (DR4) and death receptor 5 (DR5). Therefore, NF-κB activation either suppresses or promotes apoptosis depending on the type of stimulus or cell context. We showed previously that the synthetic retinoid, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), effectively induces apoptosis particularly in androgen-independent prostate carcinoma cells. This effect was associated with the ability of CD437 to induce the expression of DR4 and DR5. In the present study, we examined the hypothesis that NF-κB activation plays a role in CD437-induced death receptor expression and apoptosis. Treatment of DU145 cells with CD437 resulted in a rapid decrease (≥3 hours) of IκBα, which was accompanied by increased translocation of the NF-κB subunit p65 from the cytoplasm to the nucleus and increased NF-κB DNA-binding activity (≥4 hours). The NF-κB inhibitor, helenalin, inhibited CD437-induced IκBα reduction and p65 nuclear translocation. Accordingly, it also abrogated CD437-induced up-regulation of DR4, activation of caspase-8 and caspase-3, and increased DNA fragmentation. Overexpression of an IκBα dominant-negative mutant blocked not only CD437-induced p65 nuclear translocation but also DR4 up-regulation, caspase activation, and DNA fragmentation. CD437 was unable to decrease IκBα protein levels and up-regulate DR4 expression in CD437-resistant DU145 cells. Moreover, knockdown of Fas-associated death domain, caspase-8, and DR4, respectively, suppressed CD437-induced apoptosis. Collectively, these results indicate that CD437 activates NF-κB via decreasing IκBα protein and thereby induces DR4 expression and subsequent apoptosis in DU145 cells.
Cognitive function and other risk factors for mild traumatic brain injury in young men: nationwide cohort study
Authors: A. Nordstrom, B. B. Edin, S. Lindstrom, P. Nordstrom
Journal: BMJ (2013)

<b>Objective</b> To investigate cognitive function and other risk factors for mild traumatic brain injury in young men. <b>Design</b> Nationwide prospective cohort study. <b>Setting</b> Sweden. <b>Participants</b> 305 885 men conscripted for military service from 1989 to 1994. <b>Main outcome measure</b> mild traumatic brain injuries in relation to cognitive function and other potential risk factors assessed at conscription and follow-up. <b>Results</b> Men with one mild traumatic brain injury within two years before (n=1988) or after cognitive testing (n=2214) had about 5.5% lower overall cognitive function scores than did men with no mild traumatic brain injury during follow up (P&lt;0.001 for both). Moreover, men with at least two mild traumatic brain injuries after cognitive testing (n=795) had 15% lower overall cognitive function scores compared with those with no such injury (P&lt;0.001). Independent strong risk factors (P&lt;1×10<sup>−10</sup>) for at least one mild traumatic brain injury after cognitive testing (n=12 494 events) included low overall cognitive function, a previous mild traumatic brain injury, hospital admission for intoxications, and low education and socioeconomic status. In a sub-cohort of twin pairs in which one twin had a mild traumatic brain injury before cognitive testing (n=63), both twins had lower logical performance and technical performance compared with men in the total cohort with no mild traumatic brain injury (P&lt;0.05 for all). <b>Conclusion</b> Low cognitive function, intoxications, and factors related to low socioeconomic status were strong independent risk factors for mild traumatic brain injuries in men. The low cognitive function in twin pairs discordant for mild traumatic brain injury suggests a genetic component to the low cognitive function associated with such injuries. The study included only men, so inferences to women should be made with caution.
Observations on Decreased Serum Glutamic Oxalacetic Transaminase (SGOT) Activity in Azotemic Patients
Authors: GEORGE A. COHEN
Journal: Annals of Internal Medicine (1976)

Serum glutamic oxalacetic transaminase (SGOT) activity may be decreased or even absent in patients with uremia. We correlated urea concentration with SGOT activity by the automated Rush (AutoAnalyzer, Technicon Instruments Corp., Tarrytown, New York) method (SGOT, SMA) and by the Henry-Karmen kinetic assay (SGOT, K). Extremely low SGOT (SMA) activity (< 10 lU) was found in 6% of 5030 consecutive samples, and 71% of them occurred in patients with azotemia. SGOT activity was inversely proportional to urea concentration. A similar but less obvious pattern was observed with the SGOT (K) assay. SGOT activity increased significantly after hemodialysis in a group of 16 patients studied by both methods. It was not inhibited either by urea or uremic serum added in vitro. The explanation for this phenomenon is not known.
Suicides involving co-proxamol fell dramatically after withdrawal in UK
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The withdrawal of the analgesic co-proxamol in the United Kingdom in 2005 has led to a dramatic reduction in the numbers of suicides and accidental poisonings involving the drug, without an increase in deaths involving other analgesics, a study has found.

In the six years from 2005 there were 600 fewer suicides and cases of accidental poisoning in England and Wales involving co-proxamol than would have been expected had the drug still been available.1 On average …
Hospital Admission Through the Emergency Department
Authors: Carin M. Olson
Journal: JAMA (1991)

In this issue ofThe Journal, Stern et al 1 compare hospital charges and lengths of stay for patients admitted through the emergency department with charges and lengths of stay for patients admitted through other routes to any of five Massachusetts hospitals. Even with adjustments for diagnosis related group, severity of illness, age, and income, patients admitted through the emergency department incurred hospital charges 13% higher and hospital stays 27% longer than other patients.
TCTAP A-165 Comparison in Cardiac Remodeling Between Surgical Treatment and Device Closure of Atrial Septal Defect
Authors: You-Mi Hwang, Ji Hoon Kim, Keon Woong Moon, Ki-Dong Yoo, Chul-Min Kim, Mi-hyang Jung, Soo-Yeon Jung, Gee-Hee Kim
Journal: Journal of the American College of Cardiology (2014)
L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia.
Authors: L Liaudet, D Fishman, M Markert, C Perret, F Feihl
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Overproduction of NO by an inducible NO synthase (iNOS) plays a major role in the pathophysiology of septic shock, and selective inhibition of iNOS in this setting could be of great therapeutic value. In the present study, we evaluated the effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic shock, with a particular focus on tissue oxidative metabolism and organ functions. Anesthetized rats challenged intravenously with lipopolysacharide (LPS) were treated after 1 h by a continuous infusion of either L-canavanine (20 mg/kg/h; n = 11) or an equivalent volume of saline (2 ml/kg/h; n = 17) given for 4 h. A third group (sham rats; n = 9) did not receive LPS and was treated with a continuous infusion of saline (2 ml/kg/h). At the end of experiments, biopsies were taken from the liver, the kidney, and the small intestine for the measurement of tissue ATP. LPS induced a progressive fall in blood pressure, accompanied by biologic signs of liver and kidney failure, concomitant with a marked decrease in tissue ATP stores. L-canavanine largely prevented hypotension and significantly increased tissue ATP while reducing the signs of organ dysfunction. These effects were associated with a significant improvement in survival during the 5 h of study. We conclude that L-canavanine not only reduces hypotension in endotoxin shock but also largely prevents the detrimental consequences of LPS on tissue oxidative metabolism and major organ functions, allowing a decrease in endotoxin lethality.
The abuse of privileged children
Authors: Des Spence
Journal: BMJ (2011)

<h3>Abstract</h3> A human monoclonal antibody panel (PD4, PD5, PD7, SC23 and SC29) was isolated from the B cells of convalescent patients and used to examine the S protein in SARS-CoV-2- infected cells. While all five antibodies bound conformational-specific epitopes within SARS-CoV-2 Spike (S) protein, only PD5, PD7, and SC23 were able to bind to the Receptor Binding Domain (RBD). Immunofluorescence microscopy was used to examine the S protein RBD in cells infected with the Singapore isolates SARS-CoV-2/0334 and SARS-CoV-2/1302. The RBD-binders exhibited a distinct cytoplasmic staining pattern that was primarily localised within the Golgi complex and was distinct from the diffuse cytoplasmic staining pattern exhibited by the non-RBD binders (PD4 and SC29). These data indicated that the S protein adopted a conformation in the Golgi complex that enabled the RBD recognition by the RBD-binders. The RBD-binders also recognised the uncleaved S protein indicating that S protein cleavage was not required for RBD recognition. Electron microscopy indicated high levels of cell-associated virus particles, and multiple cycle virus infection using RBD-binder staining provided evidence for direct cell-to-cell transmission for both isolates. Although similar levels of RBD-binder staining was demonstrated for each isolate, the SARS-CoV-2/1302 exhibited slower rates of cell-to-cell transmission. These data suggest that a conformational change in the S protein occurs during its transit through the Golgi complex that enables RBD recognition by the RBD-binders, and suggests that these antibodies can be used to monitor S protein RBD formation during the early stages of infection. <h3>Importance</h3> The SARS CoV-2 spike (S) protein receptor binding domain (RBD) mediates the attachment of SARS CoV-2 to the host cell. This interaction plays an essential role in initiating virus infection and the S protein RBD is therefore a focus of therapeutic and vaccine interventions. However, new virus variants have emerged with altered biological properties in the RBD that can potentially negate these interventions. Therefore an improved understanding of the biological properties of the RBD in virus-infected cells may offer future therapeutic strategies to mitigate SARS CoV-2 infection. We used physiologically relevant antibodies that were isolated from the B cells of convalescent COVID19 patients to monitor the RBD in cells infected with SARS CoV-2 clinical isolates. These immunological reagents specifically recognise the correctly folded RBD and were used to monitor the appearance of the RBD in SARS CoV-2-infected cells and identified the site where the RDB first appears.
Endoscopic injection sclerosis: effective treatment for bleeding peptic ulcer.
Authors: C Rajgopal, K R Palmer
Journal: Gut (1991)

One hundred and nine patients presenting with severe haemorrhage from benign peptic ulcers were randomised to either endoscopic injection sclerotherapy using a combination of 1:100,000 adrenaline and 5% ethanolamine or to conservative treatment. Only high risk patients with active bleeding or endoscopic stigmata of recent haemorrhage and accessible ulcers were considered. The two groups were well matched for age, shock, haemoglobin concentration, endoscopic findings, and consumption of non-steroidal anti-inflammatory drugs. The group treated endoscopically had a significantly reduced rebleeding rate (12.5% v 47%, p less than 0.001). Rebleeding was successfully treated in some patients by injection sclerotherapy, other patients underwent urgent surgery. While there was a tendency towards a lower operation rate and lower transfusion requirements in the treated group, this failed to achieve statistical significance. The use of injection sclerotherapy in the conservatively treated group after rebleeding undoubtedly reduced the number of surgical operations. Endoscopic injection sclerotherapy is effective in the prevention of rebleeding in these patients.
Sequence-Specific Knockdown of EWS-FLI1 by Targeted, Nonviral Delivery of Small Interfering RNA Inhibits Tumor Growth in a Murine Model of Metastatic Ewing's Sarcoma
Authors: Siwen Hu-Lieskovan, Jeremy D. Heidel, Derek W. Bartlett, Mark E. Davis, Timothy J. Triche
Journal: Cancer Research (2005)

Abstract The development of effective, systemic therapies for metastatic cancer is highly desired. We show here that the systemic delivery of sequence-specific small interfering RNA (siRNA) against the EWS-FLI1 gene product by a targeted, nonviral delivery system dramatically inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. The nonviral delivery system uses a cyclodextrin-containing polycation to bind and protect siRNA and transferrin as a targeting ligand for delivery to transferrin receptor–expressing tumor cells. Removal of the targeting ligand or the use of a control siRNA sequence eliminates the antitumor effects. Additionally, no abnormalities in interleukin-12 and IFN-α, liver and kidney function tests, complete blood counts, or pathology of major organs are observed from long-term, low-pressure, low-volume tail-vein administrations. These data provide strong evidence for the safety and efficacy of this targeted, nonviral siRNA delivery system.
C-Reactive Protein and the Risk of Developing Hypertension
Authors: Howard D. Sesso
Journal: JAMA (2003)

Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce.To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension.A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected.Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP.C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.
Point of view of an overseas doctor.
Authors: A Virji
Journal: BMJ (1983)

The conventional use of the term   was coined to embrace all doctors working in the United Kingdom who had obtained their basic medical qualifications in medical schools abroad. Numerically, the largest group of overseas doctors is from the Indian subcontinent?17?0 of all doctors in the National Health Service (30?o of hospital doctors and 20''o of general practitioners). Those from white anglophone countries and Arab countries account for only 6% of all NHS doctors. Graduates from Eire are traditionally considered home grown, as are doctors born overseas who qualified in Britain. In this article the term   is used in a limited sense to define those doctors with particular ethnic, cultural, and linguistic characteristics that influence their future. The history of the overseas doctor is one of the most in? congruous and anomalous quirks of the twentieth century. How did large numbers of doctors trained in one of the poorest parts of the world end up working for one of the richest ? Most doctors came from ex-colonies of Britain, especially India where medical schools are run on the British model and students are aught in English. Substantial immigration to the United Kingdom took place in the 1950s and 1960s for several reasons, one of the most important being the lack of British graduates to fill vacancies in the NHS. Furthermore, British training and qualifications were highly regarded, and immigration of overseas doctors was facilitated by the lack of the usual entry restrictions and the recognition of their degrees by the General Medical Council. Thus having been allowed freely into Britain, these doctors discovered that the streets of Vilayat (United Kingdom) were not paved with gold as they had been led to believe. Handi? capped by cultural and linguistic differences, the unfortunate immigrant doctor was regarded as having lower standards of practice, and often his basic qualifications were questioned. Many found that the only jobs available were the unpopular junior hospital posts. In 1975 the report of the Merrison committee on the NHS voiced officially the reservations felt towards overseas doctors by the British medical profession. This resulted in the introduction of the Temporary Registration Assessment Board (TRAB) examination, which doctors who qualified overseas were now required to pass to prove their knowledge of medicine and skill with the English language. Fuelled by this development, the Overseas Doctors Association was formed officially to express the difficulties faced by its members.
Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption.
Authors: G M Rubanyi, A D Freay, K Kauser, D Sukovich, G Burton, D B Lubahn, J F Couse, S W Curtis, K S Korach
Journal: Journal of Clinical Investigation (1997)

The present study was designed to test the hypothesis that estrogen receptors (ER) in the blood vessel wall play a role in the modulation of the release of endothelium-derived nitric oxide (EDNO). Both basal and stimulated release of EDNO were determined in aortic rings isolated from female and male wild-type and male homozygous estrogen receptor knock-out (ERKO) mice. 125I-17beta-estradiol binding in aortic tissue showed significantly more high affinity cytosolic- nuclear-binding sites in male compared with female wildtype mice. Estrogen receptor transcripts were present in the aorta of male wild-type mice, but they were absent in male ERKO animals. Basal release of EDNO (determined by endothelium-dependent contraction caused by NG-nitro-arginine) was significantly higher in aorta of wild-type male mice compared with wild-type female mice, and significantly lower in the aorta of male ERKO compared with male wild-type mice. Acetylcholine-induced endothelium-dependent relaxation was similar in all groups studied. No difference was observed in the activity of calcium-dependent nitric oxide synthase in homogenates of lungs and brain taken from male wild-type and ERKO mice. These studies show a significant association between the number of estrogen receptors and basal release of EDNO in the aorta of mice, and suggest that decreased vascular estrogen receptor number may represent a novel risk factor for cardiovascular diseases.
US nurse who contracted Ebola leaves hospital
Authors: M. McCarthy
Journal: BMJ (2014)

One of the two US nurses who contracted Ebola virus disease while caring for a patient from west Africa in a hospital in Dallas, Texas, has been released from the high level bio-containment isolation unit at the National Institutes of Health’s Clinical Center in Bethesda, Maryland.

Nina Pham, 26, of Fort Worth, Texas, became infected while taking care of Eric Thomas Duncan, a 42 year old Liberian national who fell ill shortly after he traveled from west Africa to Dallas in late September. Duncan was admitted to Texas Health Presbyterian Hospital Dallas 28 September. Despite intensive care, which included ventilator support and renal dialysis, Duncan died 8 October.

Pham …
Hemodynamic effects of terbutaline, a β2-adrenoceptor agonist, in conscious rats with secondary biliary cirrhosis
Authors: Jorge L. Poo, Alain Braillon, Antoine Hadengue, Christophe Gaudin, Didier Lebrec
Journal: Hepatology (1992)

The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor agonist - were studied in conscious normal rats and in conscious rats with secondary biliary cirrhosis. Compared with those of normal rats, dose-response curves in cirrhotic rats indicated significantly decreased reactivity in arterial pressure and heart rate. Half-maximal effective dose was not significantly different between the two groups. Terbutaline induced significant, dose-dependent decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1 body wt) increased both cardiac output and portal tributary blood flow, thus mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to 22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The association of a decreased portal pressure and increased splanchnic blood flow suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal collateral vascular resistance.
Inhibition of ACE/kininase-II, acute myocardial infarction, and survival
Authors: A. S Hall, L.-B. Tan, S. G Ball
Journal: Cardiovascular Research (1994)

Journal Article Inhibition of ACE/kininase-II, acute myocardial infarction, and survival Get access Alistair S Hall, Alistair S Hall Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: A S Hall, L B Tan, S G Ball. Correspondence to Dr Hall. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lip-Bun Tan, Lip-Bun Tan Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: A S Hall, L B Tan, S G Ball. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen G Ball Stephen G Ball Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: A S Hall, L B Tan, S G Ball. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 2, February 1994, Pages 190–198, https://doi.org/10.1093/cvr/28.2.190 Published: 01 February 1994 Article history Received: 12 March 1993 Accepted: 01 July 1993 Published: 01 February 1994