tbuckley/cabot-search huggingface dataset:
Eradication of Solid Human Breast Tumors in Nude Mice with an Intravenously Injected Light-Emitting Oncolytic Vaccinia Virus
Authors: Qian Zhang, Yong A. Yu, Ena Wang, Nanhai Chen, Robert L. Danner, Peter J. Munson, Francesco M. Marincola, Aladar A. Szalay
Journal: Cancer Research (2007)

Abstract Previously, we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase–Aequorea green fluorescent protein fusion, β-galactosidase, and β-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the viral genome, respectively. I.v. injections of GLV-1h68 (1 × 107 plaque-forming unit per mouse) into nude mice with established (∼300–500 mm3) s.c. GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity, and oncolytic efficacy. GLV-1h68 showed an enhanced tumor targeting specificity and much reduced toxicity compared with its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus–mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of IFN-stimulated genes (STAT-1 and IRF-7), cytokines, chemokines, and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. [Cancer Res 2007;67(20):10038–46]
The role of nitric oxide synthases in pemphigus vulgaris in a mouse model
Authors: M. Marquina, A. España, M. Fernández-Galar, M.J. López-Zabalza
Journal: British Journal of Dermatology (2008)

Background Pemphigus vulgaris (PV) is a blistering autoimmune disease characterized by IgG autoantibodies against desmoglein 3. Nitric oxide synthases (NOS) may contribute to the increase of inflammation in tissues by the generation of nitrotyrosine residues (NTR). Objectives To investigate whether the production of NTR mediated by NOS may participate in the development of inflammation and acantholysis in PV. Methods Mice were pretreated or not with NOS, tyrosine‐kinase (TK) or nuclear factor (NF)‐κB inhibitors, and then injected with PV‐IgG. PV manifestations were examined in all mice. The expression of NTR, constitutive NOS (cNOS) [endothelial NOS (eNOS) and neuronal NOS (nNOS)], inducible NOS (iNOS) and NF‐κB factor were studied in epidermis of mice using immunohistochemical techniques. Results After PV‐IgG injection, expressions of NTR, iNOS, eNOS and nNOS increased in acantholytic cells, as did nuclear translocation of NF‐κB in the basal cells of the epidermis. Pretreatment of mice with inhibitors of TK, nNOS and nonselective NOS, completely prevented NTR expression and the clinical and histological findings of PV in mice. TK inhibitor genistein inhibited both nNOS and iNOS expression on the membrane of basal keratinocytes, and nuclear translocation of NF‐κB. Conclusions Upregulation of cNOS and iNOS, NTR generation and nuclear translocation of NF‐κB may contribute to increased inflammation and tissue damage in PV lesions. The absence of the clinical and histological findings of PV and NTR expression in mice injected with PV‐IgG, through pretreatment with TK and nNOS inhibitors, provides compelling evidence that these signalling molecules should be considered as potential therapeutic targets in PV.
Sedentary behaviour and risk of mortality from all-causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort
Authors: Josephine Y Chau, Anne Grunseit, Kristian Midthjell, Jostein Holmen, Turid Lingaas Holmen, Adrian E Bauman, Hidde P Van der Ploeg
Journal: British Journal of Sports Medicine (2013)

Background Sedentary behaviour is a potential risk factor for chronic-ill health and mortality, that is, independent of health-enhancing physical activity. Few studies have investigated the risk of mortality associated with multiple contexts of sedentary behaviour. Objective To examine the prospective associations of total sitting time, TV-viewing time and occupational sitting with mortality from all causes and cardiometabolic diseases. Methods Data from 50 817 adults aged ≥20 years from the Nord-Trøndelag Health Study 3 (HUNT3) in 2006–2008 were linked to the Norwegian Cause of Death Registry up to 31 December 2010. Cox proportional hazards models examined all-cause and cardiometabolic disease-related mortality associated with total sitting time, TV-viewing and occupational sitting, adjusting for multiple potential confounders including physical activity. Results After mean follow-up of 3.3 years (137 315.8 person-years), 1068 deaths were recorded of which 388 were related to cardiometabolic diseases. HRs for all-cause mortality associated with total sitting time were 1.12 (95% CI 0.89 to 1.42), 1.18 (95% CI 0.90 to 1.57) and 1.65 (95% CI 1.24 to 2.21) for total sitting time 4−&lt;7, 7−&lt;10 and ≥10 h/day, respectively, relative to &lt;4 h/day after adjusting for confounders (p-trend=0.001). A similar pattern of associations was observed between total sitting time and mortality from cardiometabolic diseases, but TV-viewing time and occupational sitting showed no or borderline significant associations with all-cause or cardiometabolic disease-related mortality over the same follow-up period. Conclusions Total sitting time is associated with all-cause and cardiometabolic disease-related mortality in the short term. However, prolonged sitting in specific contexts (ie, watching TV, at work) do not adversely impact health in the same timeframe. These findings suggest that adults should be encouraged to sit less throughout the day to reduce their daily total sitting time.
Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand
Authors: Junyan Han, Azzeddine Dakhama, Yi Jia, Meiqin Wang, Wanjiang Zeng, Katsuyuki Takeda, Yoshiki Shiraishi, Masakazu Okamoto, Steven F. Ziegler, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2012)
Biosensors: Rapid Detection of Hendra Virus Using Magnetic Particles and Quantum Dots (Adv. Healthcare Mater. 5/2012)
Authors: Fabio Lisi, Paolo Falcaro, Dario Buso, Anita J. Hill, Jennifer A. Barr, Gary Crameri, Tich‐Lam Nguyen, Lin‐Fa Wang, Paul Mulvaney
Journal: Advanced Healthcare Materials (2012)

Point-of-care methodologies for the rapid detection of emerging viruses are essential for combatting viral outbreaks. On page 631, P. Falcaro, L.-F. Wang, and co-workers report on progress towards the detection of the Hendra virus, based on antibody-conjugated quantum dots and antibody-conjugated magnetic particles.
Factors Associated With Breast Cancer Clinical Trials Participation and Enrollment at a Large Academic Medical Center
Authors: Michael S. Simon, Wei Du, Lawrence Flaherty, Philip A. Philip, Patricia Lorusso, Cheryl Miree, Daryn Smith, Diane R Brown
Journal: Journal of Clinical Oncology (2004)

The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials.From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment.The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%).It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.
A toxic gas eases IBD
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

A study on page 1703 might help explain why active smokers rarely suffer from an inflammatory bowel disease (IBD) known as ulcerative colitis. Hegazi and colleagues show that carbon monoxide (CO) gas, a component of cigarette smoke, shuts down the production of a disease-promoting cytokine, thus easing chronic bowel inflammation in mice.






Figure 

Inhaled carbon monoxide induces the intestinal expression of heme oxygenase-1 (dark brown) and soothes colitis.




CO is both a toxic air pollutant and a normal byproduct of cellular heme metabolism. Although CO's asphyxiant properties have earned it a bad reputation, the ubiquitous tissue expression of the natural CO-producing enzyme heme oxygenase-1 (HO-1) suggests that the effects of CO must not be all bad.

Indeed, recent studies have shown that CO, at least at low concentrations, has a redeeming quality: it acts as an antiinflammatory agent. Low dose inhaled CO is therapeutic in many acute disease models including bacterial sepsis, organ transplantation, and vascular injury. Normally, HO-1 expression (and thus CO production) is induced under conditions of cellular stress, such as infection or oxygen deprivation, probably to limit the adverse effects of stress-induced inflammation.

The effects of CO on chronic inflammation, however, had not been studied. Here, Hegazi and colleagues show that CO exposure also inhibits chronic intestinal inflammation in mice. Exogenous CO treatment induced the expression of HO-1, either directly or indirectly, which in turn limited the intestinal production of the inflammation-inducing cytokine interleukin (IL)-12. In macrophages, HO-1 inhibited the expression of the transcription factor IRF-8 (interferon regulatory factor-8), which normally drives the synthesis of IL-12 in response to bacterial lipopolysaccharide and interferon-γ—a situation that mimics the stimulation of these cells in the inflamed intestine.

Although the induction of HO-1 is required for the therapeutic effects of CO in most disease models, this is the first study to identify IRF-8 as a target of HO-1–induced inhibition. How HO-1 represses IRF-8 expression remains to be determined.

Based on these results, the authors suggest that inhaled CO or agents that increase endogenous HO-1 activity might be therapeutic in patients with ulcerative colitis. However, nonsmokers with IBD shouldn't necessarily break out the Marlboros, as cigarette smoking is a risk factor not only for heart disease and cancer but also for Crohn's disease, another form of IBD.
Mortality in relation to smoking: 40 years' observations on male British doctors
Authors: R Doll, R Peto, K Wheatley, R Gray, I Sutherland
Journal: BMJ (1994)

To assess the hazards associated with long term use of tobacco.Prospective study of mortality in relation to smoking habits assessed in 1951 and again from time to time thereafter, with causes sought of deaths over 40 years (to 1991). Continuation of a study that was last reported after 20 years' follow up (1951-71).34,439 British male doctors who replied to a postal questionnaire in 1951, of whom 10,000 had died during the first 20 years and another 10,000 have died during the second 20 years.Excess mortality associated with smoking was about twice as extreme during the second half of the study as it had been during the first half. The death rate ratios during 1971-91 (comparing continuing cigarette smokers with life-long non-smokers) were approximately threefold at ages 45-64 and twofold at ages 65-84. The excess mortality was chiefly from diseases that can be caused by smoking. Positive associations with smoking were confirmed for death from cancers of the mouth, oesophagus, pharynx, larynx, lung, pancreas, and bladder; from chronic obstructive pulmonary disease and other respiratory diseases; from vascular diseases; from peptic ulcer; and (perhaps because of confounding by personality and alcohol use) from cirrhosis, suicide, and poisoning. A negative association was confirmed with death from Parkinson's disease. Those who stopped smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered, but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke.Results from the first 20 years of this study, and of other studies at that time, substantially underestimated the hazards of long term use of tobacco. It now seems that about half of all regular cigarette smokers will eventually be killed by their habit.
Amplitude variability of the action potential in hypoxic ventricular muscle
Authors: T. WATANABE, T. F McDONALD, P. M RAUTAHARJU
Journal: Cardiovascular Research (1982)

The effect of hypoxia on the amplitude variability of the action potential in guinea pig papillary muscle was investigated by high-resolution on-line computer analysis using a 6 kHz sampling rate and a 2 kHz low pass filter. Ensembles of 50 successive action potentials were carefully aligned in time, and the amplitude variability was determined by calculating the standard deviation (SD) for each sampling point within the action potential. In oxygenated muscle, the SD was about 0.5 mV at phases 1, 2 and 4 and about 2 mV at phase 3. During hypoxia (40 to 105 min) the SD peak at phase 3 declined from the control value of 2.21 ±0.23 mV (SE, n= 11) to 1.50±0.27 mV (SE, n= 6). It is concluded that previous reports suggesting an increase of the action potential variability during hypoxia may be due to improper recording and data processing procedures.
Non-surgical treatment of gall stones: many contenders but who will win the crown?
Authors: I A Bouchier
Journal: Gut (1988)

Leading articleNon-surgical treatment of gall stones: many contenders but who will win the crown?Is gastroenterology in danger of becoming overwhelmed by a prodigality of treatments and techniques?Thirty years ago investigations comprised the biochemical analysis of blood, non-invasive radiology and a few 'function' tests needing nasogastric intubation.Therapy was often restricted to the simple decision between using a limited pharmacopoeia, or surgery.Fibreoptic endoscopy, invasive radiology and the proliferation of powerful targetted drugs have changed all this.Therapeutic alternatives abound and now instead of wondering what to do, we debate what not to do.The seductive attraction of the clinical trial all too often results in promises unfulfilled, but nevertheless has made a contribution to rational therapy.This changing scene is reflected in the many ways of managing numerous gastrointestinal disorders, such as malignant oesophageal strictures,' peptic ulcer,2 lesions of the extrahepatic biliary system3 and gall stones.The publication in 1972 of the trail blazing paper by Danzinger and his colleagues4 signalled the end of centuries of quackery.At last we had a genuine oral therapy for dissolving gall stones.Treatment with chenode- oxycholic acid for cholesterol gall stones was welcomed by a public ever fearful of surgery and it opened the door to the use of other agents, singly or in combination, to dissolve gall stones.Management options have been widened with the imaginative and highly skilled use of fibreoptic endoscopy to dissolve, crush and extract stones in the bile duct.To complete the picture we have emerging the added option ofextracorporeal shock wave lithotripsy.Most gastroenterologists are familiar with the considerations conducive to successful chenodeoxycholic acid therapy: radiolucent gall stones in a gall bladder that opacifies on oral cholecystography, stones not much larger than 15 mm in diameter and moderate symptoms.Unfortunately overall efficacy is disappointingly low, around 38%,5 but this can be improved by careful selection of patients who will comply conscientiously and are not obese, and by ensuring that during treatment bile becomes unsaturated in cholesterol.Under these conditions successful outcome can be expected in 70-75% of patients.The non-responders are probably patients who have radiolucent pigment stones which will not respond to chenodeoxycholic acid.Surface calcium salts (phosphate, bilirubinate, carbonate) and probably also the inorganic matrix67 are responsible for the failure of some radiolucent stones to dissolve.The optimal dose of chenodeoxycholic acid is 13-15 mg/kg/day, but obese patients need doses as large as 18-20 mg/kg/day before the bile becomes unsaturated.8The use of chenodeoxycholic acid is not without problems.It causes moderate abnormalities in the liver associated analytes, diarrhoea, 137on July 12,
Psychosocial Care for Family Caregivers of Patients With Cancer
Authors: Laurel Northouse, Anna-leila Williams, Barbara Given, Ruth McCorkle
Journal: Journal of Clinical Oncology (2012)

Purpose To understand family caregivers' needs for better preparation and care, this state-of-the-science review examines the effect of caregiving on the health and well-being of caregivers, the efficacy of research-tested interventions on patient and caregiver outcomes, implications of the research on policy and practice, and recommendations for practice and future research. Methods We reviewed research that described the multiple effects of cancer on caregivers' well-being. Five meta-analyses were analyzed to determine the effect of interventions with caregivers on patient and caregiver outcomes. In addition, we reviewed legislation such as the Affordable Care Act and the Family Leave Act along with current primary care practice to determine whether family caregivers' needs have been addressed. Results Research findings indicate that caregiver stress can lead to psychological and sleep disturbances and changes in caregivers' physical health, immune function, and financial well-being. Research-tested interventions delivered to caregivers of patients with cancer or other chronic illnesses can reduce many of these negative effects and improve caregivers' coping skills, knowledge, and quality of life. Although these interventions also decrease patients' symptoms, reduce mortality (non-dementia patients), and improve patients' physical and mental health, they are seldom implemented in practice. Conclusion Recommendations for practice include development of standardized guidelines that address caregiver assessment, education, and resources; identification of “caregiver champions” in practice settings; provision of referrals to established support organizations for caregivers (eg, Cancer Support Community, Cancer Care); and collaboration among caregiving, professional, and cancer-related organizations to advocate policy and practice changes for family caregivers.
Blocking NRG1 and Other Ligand-Mediated Her4 Signaling Enhances the Magnitude and Duration of the Chemotherapeutic Response of Non–Small Cell Lung Cancer
Authors: Ganapati V. Hegde, Cecile C. de la Cruz, Cecilia Chiu, Navneet Alag, Gabriele Schaefer, Lisa Crocker, Sarajane Ross, David Goldenberg, Mark Merchant, Janet Tien, Lily Shao, Leslie Roth, Siao-Ping Tsai, Scott Stawicki, Zhaoyu Jin, Shelby K. Wyatt, Richard A. D. Carano, Yanyan Zheng, E. Alejandro Sweet-Cordero, Yan Wu, Erica L. Jackson
Journal: Science Translational Medicine (2013)

Inhibition of Her4 signaling enhances the response to chemotherapy and delays tumor regrowth after cessation of treatment.
Tumor Cavitation in Patients With Stage III Non–Small-Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy: Incidence and Outcomes
Authors: Erik C.J. Phernambucq, Koen J. Hartemink, Egbert F. Smit, Marinus A. Paul, Pieter E. Postmus, Emile F.I. Comans, Suresh Senan
Journal: Journal of Thoracic Oncology (2012)
High Incidence of Rickets in Children with Wheezy Bronchitis in a Developing Country
Authors: A Sahib El-Radhi, N Mansor, M Majeed, M Ibrahim
Journal: Journal of the Royal Society of Medicine (1982)

The incidence of rickets in 100 Iraqi infants with wheezy bronchitis (24%) exceeded by two and a half times that found in age-matched controls (9%), and by ten times when only those with severe rickets were considered. The reason for this is not entirely clear, but could be related to the fact that the infants with wheezy bronchitis weighed more and therefore had grown faster than the control group. This itself could be related to the higher incidence of breastfeeding in the infants with wheezy bronchitis. We wish to stress the importance of screening for rickets, particularly in those with wheezy bronchitis.
The radiologist made the diagnosis
Authors: J R Bebb
Journal: Gut (2005)

Background and aims: Interstitial cells of Cajal (ICC) have been shown to be involved in nitrergic neurotransmission of the lower oesophageal sphincter and pylorus.Here we studied the role of ICC and nitric oxide (NO) in the inhibitory neurotransmission of the murine internal anal sphincter (IAS).Methods: The rectoanal inhibitory reflex, rectal compliance, and relaxation of the isolated IAS to electrical stimulation were measured in controls, KIT W /KIT Wv mice, and neuronal NO synthase (nNOS) deficient mice.In addition, we evaluated the effect of blockade of nNOS using N-nitro-L-arginine methyl ester.Distribution of nNOS positive neurones and ICC in the IAS was assessed immunohistochemically.Results: KIT positive ICC were present in a dense network in the IAS of controls but not in KIT W /KIT Wv mice.Relaxation of IAS muscle strips induced by electrical stimulation was diminished in nNOS 2/2 mice but not in KIT W /KIT Wv mice.Blockade of NOS reduced the relaxation of IAS muscle strips in both mice.Relaxation of the IAS to rectal distension was significantly diminished in KIT W /KIT Wv mice and nNOS deficient mice.In concert, in vivo blockade of NOS attenuated the relaxation of the IAS in controls.No significant difference in compliance was found. Conclusion:The inhibitory innervation of the IAS and the rectoanal inhibitory reflex are mediated by NO and the rectoanal inhibitory reflex requires an intact network of ICC in the IAS.Thus both loss of nitrergic innervation and deficiency of ICC lead to impaired anal relaxation and may play an important role in rectal evacuation disorders.
66 SILEN-C2: SUSTAINED VIROLOGIC RESPONSE (SVR) AND SAFETY OF BI201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (P/R) IN CHRONIC HCV GENOTYPE-1 PATIENTS WITH NON-RESPONSE TO P/R
Authors: M.S. Sulkowski, M. Bourliere, J.-P. Bronowicki, A. Streinu-Cercel, L. Preotescu, T. Asselah, J.-M. Pawlotsky, S. Shafran, S. Pol, F.A. Caruntu, S. Mauss, D. Larrey, C. Häfner, Y. Datsenko, J.O. Stern, R. Kubiak, W. Böcher, G. Steinmann
Journal: Journal of Hepatology (2011)