tbuckley/cabot-search huggingface dataset:
Antitumor Activity of Hu14.18-IL2 in Patients With Relapsed/Refractory Neuroblastoma: A Children's Oncology Group (COG) Phase II Study
Authors: Suzanne Shusterman, Wendy B. London, Stephen D. Gillies, Jacquelyn A. Hank, Stephan D. Voss, Robert C. Seeger, C. Patrick Reynolds, Jennifer Kimball, Mark R. Albertini, Barrett Wagner, Jacek Gan, Jens Eickhoff, Kenneth B. DeSantes, Susan L. Cohn, Toby Hecht, Brian Gadbaw, Ralph A. Reisfeld, John M. Maris, Paul M. Sondel
Journal: Journal of Clinical Oncology (2010)

The hu14.18-IL2 fusion protein consists of interleukin-2 molecularly linked to a humanized monoclonal antibody that recognizes the GD2 disialoganglioside expressed on neuroblastoma cells. This phase II study assessed the antitumor activity of hu14.18-IL2 in two strata of patients with recurrent or refractory neuroblastoma.Hu14.18-IL2 was given intravenously (12 mg/m(2)/daily) for 3 days every 4 weeks for patients with disease measurable by standard radiographic criteria (stratum 1) and for patients with disease evaluable only by [(123)I]metaiodobenzylguanidine (MIBG) scintigraphy and/or bone marrow (BM) histology (stratum 2). Response was established by independent radiology review as well as BM histology and immunocytology, and durability was assessed by repeat evaluation after more than 3 weeks.Thirty-nine patients were enrolled (36 evaluable). No responses were seen in stratum 1 (n = 13). Of 23 evaluable patients in stratum 2, five patients (21.7%) responded; all had a complete response (CR) of 9, 13, 20, 30, and 35+ months duration. Grade 3 and 4 nonhematologic toxicities included capillary leak, hypoxia, pain, rash, allergic reaction, elevated transaminases, and hyperbilirubinemia. Two patients required dopamine for hypotension, and one patient required ventilatory support for hypoxia. Most toxicities were reversible within a few days of completing a treatment course and were expected based on phase I results.Patients with disease evaluable only by MIBG and/or BM histology had a 21.7% CR rate to hu14.8-IL2, whereas patients with bulky disease did not respond. Hu14.18-IL2 warrants further testing in children with nonbulky high-risk neuroblastoma.
Crohn's disease and pregnancy.
Authors: R Khosla, C P Willoughby, D P Jewell
Journal: Gut (1984)

Infertility and the outcome of pregnancy has been examined in 112 married women with Crohn9s disease who were below the age of 45 years. Fifty four patients were available for study. The infertility rate (12%) was similar to that seen in the general population. Patients who had active disease at the time of conception continued to have symptoms and they mostly failed to go into satisfactory remission despite therapy. Furthermore, there was a high rate (35%) of spontaneous abortion in this group. In contrast, patients whose disease was in remission at the time of conception had a normal pregnancy and, in the majority, the Crohn9s disease remained quiescent.
Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF
Authors: J. Navarro, M. Rainisio, H.K. Harms, M.E. Hodson, C. Koch, G. Mastella, B. Strandvik, S.G. McKenzie
Journal: European Respiratory Journal (2001)

The European Epidemiologic Registry of Cystic Fibrosis began collecting longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional analysis was performed to identify the factors associated with low values of % predicted forced expiratory volume in one second (FEV 1 ) upon patient enrolment. Data from 7,010 patients aged ≥6 yrs were included. Clinical conditions, microbiological isolates and medications reported at enrolment or within the following 180 days were analysed for age-specific associations. Factors associated with FEV 1 that were lower by &gt;10% of pred values were: lower weight for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at presentation, Pseudomonas aeruginosa , Burkholderia cepacia , oral corticosteroids, nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation and, in patients &gt;12 yrs old only, use of airway clearance techniques, inhaled bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or oral hypoglycaemics. Slightly impaired lung function (5–10%) was associated with: diabetes (≥18-yrs-old), gastro-oesophageal reflux, allergic bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension, Aspergillus spp. and Candida spp. Sex, Haemophilus influenzae and Staphylococcus aureus were not associated with impaired pulmonary status. Regular exercise (especially in older patients) and nasal polyposis were associated with slightly better FEV 1 . The results confirm those of previous studies and suggest selective prescribing in sicker patients.
How Much Can We Rely on the Level of Prostate-Specific Antigen as an End Point for Evaluation of Clinical Trials? A Word of Caution!
Authors: M. A. Eisenberger, W. G. Nelson
Journal: JNCI Journal of the National Cancer Institute (1996)

of PSA levels. The study objectives were to determine whether serum PSA changes were associated with the survival duration and to define the role of PSA levels as a surrogate end point for response to suramin treatment. The results, similar to those reported by others (9), indicated that a decline in PSA levels was a weak, but statistically significant, predictor of survival duration. Further evaluation of the data collected within the context of a landmark analysis (10), however, failed to identify a threshold value that would permit use of PSA-level decline as a response indicator. Thus, serum PSA levels, at least at this time, may not be the optimum marker of treatment response in advanced hormone-refractory prostate cancer. It is interesting that the statistical analyses by Sridhara et al. (8) also revealed that a 75% or greater decline in PSA levels was not more predictive of survival duration than was a 50% decline in PSA levels. Although this result may imply that suramin responses may not affect survival duration, this could also be explained by a possible confounding biological effect of suramin on PSA expression, not necessarily indicative of antitumor activity, as was suggested by Thalmann et al. (5). Clearly, more clinical data are needed to further characterize the significance of PSA changes with regard to the therapeutic benefits of suramin on prostate cancer. To this end, suramin is being tested in a prospectively randomized, placebo-controlled, multi-institutional study sponsored by Parke-Davis, Ann Arbor, MI, in which quality of life, time to disease progression, survival duration, and serial changes in PSA levels are being evaluated simultaneously. The implications of the study by Thalmann et al. (5) may actually be even broader than asserted by the authors, since similar effects on PSA expression have been reported with other drugs, including agents commonly used to treat prostate cancer, such
Fitness, Fatness, and Survival in Adults With Prediabetes
Authors: Paul A. McAuley, Enrique G. Artero, Xuemei Sui, Carl J. Lavie, M. Joao Almeida, Steven N. Blair
Journal: Diabetes Care (2013)

OBJECTIVE The purpose of this study was to examine independent and joint associations of cardiorespiratory fitness (CRF) and different adiposity measures with mortality risk in individuals with prediabetes (or impaired fasting glucose). RESEARCH DESIGN AND METHODS We examined associations of CRF and fatness with cardiovascular disease (CVD) and all-cause mortality in a cohort of 17,044 participants (89% men) with prediabetes (defined as 100 mg/dL ≤ fasting plasma glucose &amp;lt; 126 mg/dL), who did not have a history of diabetes, CVD, or cancer. RESULTS We identified 832 deaths (246 from CVD) during 13.9 ± 7.0 years (mean ± SD) follow-up. Normal-weight individuals who were unfit (lowest one-third) had a higher risk of all-cause (hazard ratio 1.70 [95% CI 1.32–2.18]) and CVD (1.88 [1.13–3.10]) mortality compared with the normal-weight and fit (upper two-thirds) reference group in a model adjusted for age, sex, examination year, and multiple risk factors. The mortality risk for fit individuals who were overweight or obese did not differ significantly from the reference group. Similar patterns were observed for sex-specific thirds of waist circumference and % body fat. CONCLUSIONS CRF markedly modifies the relationship between adiposity and mortality in persons with prediabetes. Unfit individuals have a higher and fit individuals have a lower mortality risk irrespective of adiposity level in this high-risk group.
Abstract 4227: PARP inhibitors sensitize glioblastoma stem cells to oncolytic herpes simplex virus therapy
Authors: Jianfang Ning, Hiroaki Wakimoto, Robert Martuza, Samuel Rabkin
Journal: Cancer Research (2015)

Abstract Glioblastoma (GBM) is an invariably fatal brain tumor in adults and remains a great challenge for preclinical and clinical research. PARP inhibitors (PARPi) have been used alone or in combination with genotoxic agents for the treatment of cancers with homologous recombination (HR) repair deficiencies. Oncolytic herpes simplex viruses (oHSVs) are genetically-engineered to selectively replicate in cancer cells, and previous studies have shown that oHSV infection of glioblastoma stem cells (GSC) induces DNA damage and compromises HR DNA repair. Therefore, we hypothesized that PARPi and oHSV would synergistically kill GSCs through inducing lethal DNA damage. Here, we show that PARPi consistently inhibited PARylation in a panel of patient-derived GSC lines. Surprisingly, half of GSCs (4 of 8) were sensitive to PARPi killing, with the other half being resistant. When combined with 2 different oHSVs, MG18L and G47Δ, PARPi olaparib and oHSV synergistically killed olaparib-sensitive GSCs in vitro. Moreover, olaparib sensitized PARPi-resistant GSCs to the cytotoxic effects of MG18L or G47Δ, leading to increased DNA damage and cell death. While monotherapy with systemic olaparib or intratumoral injection of MG18L increased survival in an orthotopic xenograft model generated with olaparib-sensitive GSCs, combination treatment greatly extended survival over either monotherapy alone, with concomitant induction of robust DNA damage and apoptosis in the tumors. Furthermore, in an orthotopic model with olaparib-resistant GSCs, in which olaparib monotherapy was not effective, combinatorial therapy of olaparib and MG18L was significantly more efficacious than MG18L alone in prolonging lifespan. Our studies demonstrate that PARPi have anti-GSC activity in about half of GBMs tested, and combining PARPi with oHSV targets DNA damage responses and induces a synthetic lethal effect in vitro and in vivo against both PARPi-sensitive and -resistant GSCs. This report describes a new therapeutic strategy for GBM and supports investigations of this combination in the clinic. Citation Format: Jianfang Ning, Hiroaki Wakimoto, Robert Martuza, Samuel Rabkin. PARP inhibitors sensitize glioblastoma stem cells to oncolytic herpes simplex virus therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4227. doi:10.1158/1538-7445.AM2015-4227
Role of Intracellular Na <sup>+</sup> Kinetics in Preconditioned Rat Heart
Authors: Kenichi Imahashi, Tsunehiko Nishimura, Jun Yoshioka, Hideo Kusuoka
Journal: Circulation Research (2001)

To elucidate the role of intracellular Na(+) kinetics in the mechanism for ischemic preconditioning (IPC), we measured intracellular Na(+) concentration ([Na(+)](i)) using (23)Na-magnetic resonance spectroscopy in isolated rat hearts. IPC significantly delayed the initial [Na(+)](i) increase (d[Na(+)](i)/dt) compared with non-IPC control, resulting in attenuation of Na(+) accumulation (Delta[Na(+)](i)) during 27 minutes of ischemia with better functional recovery. [Na(+)](i) in IPC, but not in control, recovered to preischemic level during a 6-minute reperfusion. The Na(+)-H(+) exchange inhibitor further suppressed d[Na(+)](i)/dt in both control and IPC hearts with concomitant improvement of functional recovery, suggesting little contribution to the mechanism of IPC. The mitochondrial ATP-sensitive K(+) (mito K(ATP)) channel activator diazoxide (30 micromol/L) completely mimicked both [Na(+)](i) kinetics and functional recovery in IPC without any additive effects to IPC. The mito K(ATP) channel blocker 5-hydroxydecanoic acid (100 micromol/L) lost protective effect as well as the attenuation of d[Na(+)](i)/dt and [Na(+)](i) recovery induced by diazoxide. However, 5-hydroxydecanoic acid also lost IPC-induced protection, but incompletely abolished the alteration of d[Na(+)](i)/dt and the [Na(+)](i) recovery. The Na(+)/K(+)-ATPase inhibitor ouabain (200 micromol/L) did not change d[Na(+)](i)/dt in non-IPC hearts, but it abolished the IPC- or diazoxide-induced reduction of d[Na(+)](i)/dt and the [Na(+)](i) recovery, whereas IPC followed by ouabain treatment showed partial functional recovery with smaller Delta[Na(+)](i) than other ouabain groups. In conclusion, alteration of Na(+) kinetics by preserving Na(+) efflux via Na(+)/K(+)-ATPase mediated by mito K(ATP) channel activation mainly contributes to functional protection in IPC hearts. The contribution of mito K(ATP) channel-independent pathway relating to Na(+) kinetics including reduced Na(+) influx is limited in functional protection of IPC.
Percutaneous Nephrolithotomy Versus Retrograde Intrarenal Surgery: A Systematic Review and Meta-analysis
Authors: Shuba De, Riccardo Autorino, Fernando J Kim, Homayoun Zargar, Humberto Laydner, Raffaele Balsamo, Fabio C Torricelli, Carmine Di Palma, Wilson R Molina, Manoj Monga, Marco De Sio
Journal: European Urology (2014)
Apoptotic response of eosinophils in chronic eosinophilic pneumonia
Authors: N. Saita, T. Yamanaka, H. Kohrogi, M. Ando, M. Hirashima
Journal: European Respiratory Journal (2001)

To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The survival rate of eosinophils and the percentage of apoptotic cells of both types of eosinophils were examined, and the effects of interleukin 5 (IL-5) were evaluated. The role of Fas expression in apoptosis of these eosinophils was also studied. The survival rate of BAL-Eos on the third day of culture was significantly higher than that of PB-Eos (p < 0.01). This was associated with a lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4% and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic character of BAL-Eos differed from that of PB-Eos in at least three ways. Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h of incubation, whereas that on BAL-Eos did not change. Secondly, the expression of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05), whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/- 1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos, but not of BAL-Eos. These data suggested that Fas seemed to be involved in the apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by proinflammatory cytokines such as IL-5 leading to their accumulation in the lung. Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a crucial role chronic eosinophilic disorders.
Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin
Authors: R. Riekki, A. Jukkola, M-L. Sassi, M. Höyhtyä, M. Kallioinen, J. Risteli, A. Oikarinen
Journal: British Journal of Dermatology (2000)

Journal Article Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin Get access R. Riekki, R. Riekki Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar A. Jukkola, A. Jukkola Oncology, University of Oulu, FIN 90220 Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar M‐L. Sassi, M‐L. Sassi Departments of Clinical Chemistry and Search for other works by this author on: Oxford Academic Google Scholar M. Höyhtyä, M. Höyhtyä Diabor Ltd, Kiviharjuntie, FIN 90220 Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar M. Kallioinen, M. Kallioinen Pathology, Oulu University Hospital, FIN 90220 Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar J. Risteli, J. Risteli Departments of Clinical Chemistry and Search for other works by this author on: Oxford Academic Google Scholar A. Oikarinen A. Oikarinen Departments of Dermatology and Professor A.Oikarinen. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 874–880, https://doi.org/10.1046/j.1365-2133.2000.03465.x Published: 01 May 2000
Causes of Death and Influencing Factors in Patients With Atrial Fibrillation
Authors: Eloi Marijon, Jean-Yves Le Heuzey, Stuart Connolly, Sean Yang, Janice Pogue, Martina Brueckmann, John Eikelboom, Ellison Themeles, Michael Ezekowitz, Lars Wallentin, Salim Yusuf
Journal: Circulation (2013)

Atrial fibrillation is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy. The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113 patients (age, 71.5 ± 9 years; male, 64%; CHADS2 score, 2.1 ± 1) to receive dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was achieved in 99.9% of patients. All deaths were categorized by the investigators using prespecified definitions followed by central adjudication. Overall, 1371 deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64-4.05). Cardiac deaths (sudden cardiac death and progressive heart failure) accounted for 37.4% of all deaths, whereas stroke- and hemorrhage-related deaths represented 9.8% of the total mortality. An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95% CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15; P=0.638). The two strongest independent predictors of cardiac death in this population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001), and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62; P<0.0001). The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population. These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
(25) Cicatricial alopecia? Cause
Authors: R.C.D. Staughton, G.C. Wells
Journal: British Journal of Dermatology (1974)

Journal Article (25) Cicatricial alopecia? Cause Get access R.C.D. Staughton, R.C.D. Staughton St Thomas' Hospital, London Search for other works by this author on: Oxford Academic Google Scholar G.C. Wells G.C. Wells St Thomas' Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 76–78, https://doi.org/10.1111/j.1365-2133.1974.tb12527.x Published: 01 July 1974
Measurement of anti-DNA antibodies: a reappraisal using five different methods.
Authors: D A Isenberg, C Dudeney, W Williams, I Addison, S Charles, J Clarke, A Todd-Pokropek
Journal: Annals of the Rheumatic Diseases (1987)

One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). In most of the assays 3-9% of the controls were positive. When the SLE sera were analysed according to disease activity the IgG anti-dsDNA ELISA, all three RIA values, and the Crithidia test values were raised in all the patients with severely active disease. Some patients with inactive disease, however, were positive in each of the tests. The best interassay correlations (r less than 0.49) were found between RIA (UK), and ss IgG and the Amersham kit; and between ds IgG and ss IgG. In the main, however, it was clear that different assays are dependent upon distinctive properties of DNA antibodies. It seems inevitable that most major rheumatology units will require more than one anti-DNA antibody assay.
Dimethylfumarate inhibits CXCL10 via haem oxygenase-1 in airway smooth muscle
Authors: Petra Seidel, Katrin E. Hostettler, J. Margaret Hughes, Michael Tamm, Michael Roth
Journal: European Respiratory Journal (2012)

CXCL10 stimulates mast cell infiltration into airway smooth muscle bundles and, thus, activate cytokine secretion and airway smooth muscle cell (ASMC) proliferation. Dimethylfumarate (DMF) reduces cytokine secretion by lymphocytes and ASMC proliferation through haem oxygenase (HO)-1. Therefore, we investigated the potency of DMF to inhibit tumour necrosis factor (TNF)-α- and interferon (IFN)-γ-induced CXCL10 secretion by human ASMCs. Human primary ASMCs were pre-incubated with DMF and/or fluticasone and/or glutathione ethylester before cells were stimulated with IFN-γ and/or TNF-α. DMF inhibited CXCL10 secretion and increased HO-1 levels, and p38 mitogen-activated protein kinase (MAPK) inhibition reduced DMF-dependent HO-1 expression. The DMF effect on CXCL10 secretion was abrogated by pre-treatment with HO-1 small interfering RNA (siRNA). Glutathione supplementation reversed all DMF effects on CXCL10 secretion and p38 MAPK phosphorylation. Importantly, combining DMF with fluticasone further reduced CXCL10 secretion. In addition, DMF inhibited IFN-γ-induced CXCL10 secretion. This effect was compensated by glutathione supplementation or by pre-treatment with HO-1 siRNA. In addition, DMF reduced TNF-α-induced granulocyte colony-stimulating factor (G-CSF) secretion but had no effect on INF-γ-induced G-CSF secretion. In human primary ASMCs, DMF inhibits CXCL10 secretion by reducing the cellular glutathione level and by activation of p38 MAPK and HO-1. Therefore, DMF may reduce airway inflammation in asthma by a glucocorticoid-independent pathway.
Tackle substance misuse in young people early, says NICE
Authors: Adrian O'Dowd
Journal: BMJ (2007)

New standards to help prevent vulnerable children and young people from getting involved in substance misuse are being launched for clinicians and non-clinicians alike.

Standards from the National Institute for Health and Clinical Excellence (NICE) call for anyone who works with young people to identify those who are vulnerable to drug problems and to intervene at the earliest opportunity.

NICE wants to help young people before they start using drugs or before they get into more serious problems if they are already misusing substances.

The guidance gives advice on stepping in and helping young people access appropriate support …