tbuckley/cabot-search huggingface dataset:
Temozolomide and IL13-Pseudomonas exotoxin act synergistically in eliminating human glioblastoma tumors in nude mice
Authors: Syed R. Husain, Raj K. Puri
Journal: Cancer Research (2005)

680   Malignant gliomas in particular glioblastoma multiforme (GBM) are the most insidious types of brain tumor. Because of their infiltrative nature and migrating phenotype, they cause nearly 14,000 deaths in the US alone. We have previously reported that IL13-PE, a chimeric protein composed of human IL-13 and a mutated form of  Pseudomonas  exotoxin specifically targets the receptor for immune cytokine, interleukin-13 (IL-13) abundantly expressed on glioma cells. Convection-enhanced delivery of IL13-PE is currently studied in a Phase 3 PRECISE trial in patients with recurrent GBM. Temozolomide (TMZ), an approved drug for anaplastic astrocytoma, acts by methylating guanosine nucleotides of DNA. The combination of TMZ (25 μg/mL) and IL13-PE (0.1 ng/mL) inhibited protein synthesis in U251MG cells by 31%, however each drug alone could inhibit 0.8% and 4.9% synthesis, respectively. In U87MG cells, TMZ (1 μg/mL) in combination with IL13-PE (62.5 ng/mL) inhibited 50% of protein synthesis. The same concentration of individual TMZ and IL13-PE inhibited synthesis by only 20% and 35%, respectively. Daily (qd) oral (p.o.) administration of one half of the clinical dose of either TMZ (2.5 mg/kg) or sub-optimal intratumoral (IT) IL13-PE (10 or 25 μg/kg) did not produce any complete responder (CR) in nude mice bearing subcutaneous 251MG tumors. Nevertheless, a combination of TMZ with 10 μg/kg IL13-PE produced 1/6 CR and 25 μg/kg gave 2/6 CRs. A similar combination of TMZ (2.5 mg/kg, qd x 5, p.o) and IL13-PE (100 μg/kg, qd x 5, IT) produced 2/5 CRs in U87MG xenografts. IT injections of IL13-PE alone did not display any CR, but oral TMZ alone produced 1/6 CR. Data clearly indicate that the combination of sub-optimal concentration of each drug acts synergistically to produce CRs and reduce tumor burden in mice with partial response. Therapy using a combination of these drugs, which act through different mechanisms, may be a beneficial treatment option for patients with brain tumor.
Abstract 12067: Remaining High Risk of Adverse Outcome and Undertreatment with Anticoagulants at Atrial Fibrillation in Acute Myocardial Infarction
Authors: Gorav Batra, Tomas Jernberg, Per Johansson, Lars C Wallentin
Journal: Circulation (2011)

Background Increased use of percutaneous coronary intervention (PCI) and dual antiplatelet treatment have improved overall outcome in acute myocardial infarction (MI). However, eventual changes in ...
Abstract 849: The changing role of GDF15 (growth/differentiation factor 15) during prostate carcinogenesis
Authors: Benjamin A. Rybicki, Dhananjay Chitale, Nilesh Gupta, LaToya Jackson, Travis Wheeler, Sheri Trudeau, Michelle Jankowski, Kevin Bobbittt, Andrew Rundle, Delian Tang
Journal: Cancer Research (2015)

Abstract GDF15 (growth/differentiation factor 15) is a divergent member of the TGFβ superfamily of cytokines and is highly expressed in prostate tumors, but its role in prostate carcinogenesis and utility as a prognostic biomarker is unclear. We studied 58 prostate cancer cases (35 Whites and 23 African Americans) that underwent surgery as their primary treatment and were then subsequently followed for biochemical recurrence (BCR). In these cases, which also had a benign prostate biopsy at least one year before their prostate cancer diagnosis, we quantified GDF15 expression in their pre-malignant benign prostate, prostate tumor and tumor adjacent benign prostate tissue. GDF15 expression levels were analyzed for association with high grade prostate cancer and BCR. Twenty-six percent of cases had high grade cancer defined as Gleason score 8 or higher or a Gleason score of 7 and a primary Gleason of 4. During follow-up, 11 cases (19%) experienced BCR (80 percent of men without BCR had at least 2 years of follow-up). GDF15 expression was not associated high grade cancer in any prostate tissue types. GDF15 expression was associated with BCR, but the direction of the association was dependent upon the type of prostate tissue expression measured. Evidence of GDF15 expression in pre-malignant benign prostate was associated with an almost 9-fold increased risk of BCR (Hazard Ratio (HR) = 8.90; 95% confidence interval (CI) = 1.09-72.49), even after adjusting for race, tumor grade and stage. When we stratified men into low and high expression groups, we also found a significant gradient of risk with increased GDF15 expression (p = 0.03). The opposite was found for GDF15 expression in tumor tissue, where men with low GDF15 expression had a decreased risk of BCR (HR = 0.30; 95% CI = 0.06- 1.59), and men with high GDF15 expression were at an even lower risk (HR = 0.10; 95% CI = 0.02-0.61). Expression of GDF15 in tumor adjacent benign prostate tissue was not associated with BCR. The role GDF15 plays in prostate carcinogenesis is complex and may change during the course of tumor development. Our results suggest GDF15 exerts a pro-tumorgenic effect very early in prostate carcinogenesis, but later after the tumor becomes clinically apparent, GDF15 may act more in an anti-tumorgenic manner. Citation Format: Benjamin A. Rybicki, Dhananjay Chitale, Nilesh Gupta, LaToya Jackson, Travis Wheeler, Sheri Trudeau, Michelle Jankowski, Kevin Bobbittt, Andrew Rundle, Delian Tang. The changing role of GDF15 (growth/differentiation factor 15) during prostate carcinogenesis. [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 849. doi:10.1158/1538-7445.AM2015-849
Abstract 15185: Impact of Sympathetic Activity and Fibrosis on Microvascular Function in Hypertrophic Cardiomyopathy
Authors: Oliver Gaemperli, Catherine Gebhard, Rory O'Hanlon, Tevfik Ismail, Ricardo Wage, Susan Clark, Paolo G Camici, Sanjay Prasad, Ornella E Rimoldi
Journal: Circulation (2010)

Purpose: In patients with hypertrophic cardiomyopathy (HCM), positron emission tomography (PET) and cardiac magnetic resonance (CMR) are potentially useful tools for risk stratification. We therefo...
Expression of programmed cell death ligand-1 in mastocytosis correlates with disease severity
Authors: Anja Rabenhorst, Silke Leja, Juliana Schwaab, Manuela Gehring, Anja Förster, Michel Arock, Andreas Reiter, Ulrike Raap, Karin Hartmann
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 19082: Cardiac Events and Mortality During Admissions for Delivery in Women with Congenital Heart Disease
Authors: Robert M Hayward, Elyse Foster, Zian H Tseng
Journal: Circulation (2014)

Background: Labor, delivery, and the postpartum period are a time of increased arrhythmia and congestive heart failure (CHF) incidence. With improvements in the treatment of congenital heart disease (CHD), more women are reaching childbearing age and may be at increased risk for cardiac events and mortality during pregnancy and delivery. Methods: The Healthcare Cost and Utilization Project was used to identify admissions for vaginal and cesarean delivery in California hospitals between 1/1/2005 and 12/31/2011. We compared length of stay, in-hospital mortality, incident CHF, cardiac arrest, and incident arrhythmias for women without CHD to women with non-complex CHD (NC-CHD) and complex CHD (C-CHD). Results: We identified 2,720,980 deliveries resulting in 2,770,382 live births (74% of live births in the state over this period), which included 3,218 women with NC-CHD and 248 women with C-CHD. History of CHF was more common in women with CHD (8.1% for C-CHD, 2.6% for NC-CHD, and 0.08% for women without CHD, p&lt;0.00005 for NC-CHD compared to no CHD and for C-CHD compared to no CHD). Those with CHD were more likely to undergo cesarean section (Table 1). Length of stay was significantly longer in women with CHD (2.6 ± 2.3 days for women without CHD, 3.4 ± 10.2 days for women with NC-CHD and 5.0 ± 13.3 days for women with C-CHD). In-hospital mortality was not significantly higher in women with CHD (Table 1). Incident heart failure, arrhythmias, and cardiac arrest were uncommon in all groups (Table 1). Conclusions: In this study of 2.7 million women admitted to California hospitals for delivery, women with CHD were more likely to undergo cesarean section and had longer length of stay. Despite more frequent history of CHF in women with CHD, incident CHF and arrhythmias were rare during hospitalization. In-hospital mortality and cardiac arrest were not higher in CHD patients. These results suggest that in pregnant women with CHD, cardiac events and mortality at the time delivery are uncommon.
Abstract 12335: Vitamin D Supplementation in Healthy Adults Lowers Plasma Thrombospondin-1 Levels: A Novel Vitamin D Target?
Authors: Anjalee T Amarasekera, Marilyn Black, Else Jansen, Greer Dymmott, Michael S Roberts, Yuliy Chirkov, John D Horowitz, Doan T Ngo
Journal: Circulation (2013)

Introduction: Vitamin D deficiency is increasingly prevalent in the general population and is associated with cardiometabolic dysfunction. Thrombospondin-1 (TSP-1) is a potent inhibitor of the nitr...
Menstrual cycle phase-related changes in appetite in patients with premenstrual syndrome and in control subjects
Authors: B Both-Orthman, D R Rubinow, M C Hoban, J Malley, G N Grover
Journal: American Journal of Psychiatry (1988)

Menstrual cycle phase-dependent changes in appetite in women with premenstrual syndrome has not thus far been systematically demonstrated. In this study of 21 patients with premenstrual syndrome and 13 control subjects, there were significant increases in appetite in both groups, with a greater effect of menstrual cycle phase on appetite in the patients. Further, the premenstrual increase in appetite was highly correlated with self-ratings of mood (particularly depression) in the patients only. The authors discuss these findings with respect to endocrine influences on appetite regulation and potential implications for investigation of atypical depression.
Abstract 16090: EMS Transport of STEMI Patients Shortens Ischemic Time and is Associated With a Higher Risk Population: Results from the ACTION Registry.
Authors: James J McCarthy, Yashwant Chathampally, Colin Barker, Matthew T Roe, Anita Y Chen, Patrik Doshi, Ali E Denktas, Richard W Smalling
Journal: Circulation (2011)

Background: Continued quality improvement efforts have had a positive impact on Door to Balloon (D2B) times for STEMI patients. Pre-hospital ischemic time has historically received little attention...
Abstract 18917: High Overweight and Obesity Rates in Fontan Patients: a Twenty-Year History
Authors: Stephanie T Chung, Borah J Hong, Lance W Patterson, Christopher J Petit, Jee-Young N Ham
Journal: Circulation (2012)

Background: Elevated body mass index (BMI) is a major independent risk factor for cardiovascular disease. The prevalence of obesity in patients with Fontan physiology is unknown and the added disease burden is unclear. There are no longitudinal studies on weight trends in Fontan patients. Objective: To determine the prevalence of overweight (OW) and obesity (OB) and to track longitudinal changes in BMI in children and adults treated with Fontan palliative surgery at a major tertiary care center. Design and Methods: We performed a retrospective chart review of all patients who underwent the Fontan operation between 1992 - 2012. Subjects were categorized by age as outlined by the NHANES database (2-5 y, 6-11 y, 12-19 y, adults) and growth records were reviewed. BMI percentiles were calculated for children using the US Centers for Disease Control (CDC) growth charts. CDC definitions of OW and OB were used. Results: Anthropometric data were available for 701 subjects (n=401, age 2-5 y; n= 333, age 6-11 y; n=217, age 12-19 y; and n=128, adult). Among adults, 38% (n=49) were OW or OB at last clinic visit, with 21.1% (n=27) OW and 17.2% (n=22) OB. Longitudinal data were available for 83 adult subjects. Of this subset, 14.5% (n=12) were OW or OB in childhood, 85.5% (n=71) had BMI &lt; 85th percentile. Forty seven percent of OB adults were OW or OB in childhood (n=9/19). The likelihood of being OW/OB as an adult was 2.5 times higher if there was OW/OB present during childhood (CI 1.8-3.6, p =&lt;0.001). Within children, the total rates of OW and OB in age groups 2-5 y, 6-11 y and 12-19 y were 24.7% (n=99), 26.4% (n=88) and 13.3% (n=29), respectively. Childhood OB rates were 13.4 % (n=54), 12% (n=40), and 4.6% (n=10), respectively, compared to national obesity rates of 10.4%, 19.6%, and 18.1% (NHANES 2007-2008). Conclusion: In this high-risk population, obesity rates for adults are nearly as high as those reported in national data, and are higher than national rates for children ages 2-5y. Longitudinal data in adult Fontan patients show that increased weight begins in childhood. The impact of early-onset obesity especially in young children with complex congenital heart disease is unknown. Assessment of the additional disease burden of obesity in this population requires additional study.
Richard Pell-Ilderton
Authors: Rosie Pell-Ilderton
Journal: BMJ (2015)

Richard Pell-Ilderton (known to friends and colleagues as Dick) was born in Ashton-under-Lyne, Lancashire, in 1921 and left school at 16. He worked briefly in a bank before joining the 2nd/9th Manchester Regiment at the outbreak of the second world war. In 1942 he was ordered to the Far East to serve in Sir Bill Slim’s “forgotten army.” …
Abstract 2972: Permanent Atrial Pacing Lead Implantation Route After Fontan Operation
Authors: Kazuhiro Takahashi, Frank Cecchin, Elizabeth B Fortescue, Charles I Berul, Mark E Alexander, Edward P Walsh, Francis Francis Fynn-Thompson, John K Triedman
Journal: Circulation (2007)

Background: Atrial pacing is commonly used for sinus node dysfunction (SND) after Fontan surgery. The preferred route of lead implant has been debated. We compare procedural and clinical outcomes of transvenous (TV) and epicardial (Epi) atrial lead implants in this population. Methods: All Fontan patients having an atrial lead implant without other associated surgery between 1992 and 2007 were studied. Demographics, pacing lead performance data and procedural outcome were retrospectively analyzed. Results: 78 patients (22 TV and 56 Epi) had 90 leads implanted (25 TV/ 65 Epi). Mean follow-up was 3.3±4.1 yrs (TV) and 4.4±3.6 yrs (Epi). TV leads were implanted in older patients (mean age: 23.9 vs. 13.8 yrs, p&lt;0.001), at longer interval after Fontan surgery (mean: 15.1 vs. 5.7 yrs, p&lt;0.001). Indication for TV was more likely to be SND, while Epi pacing was indicated for AV block. Pacing modes were exclusively AAI/AAI-T in TV and mostly DDD in Epi leads. Acute complication occurred in 2/25 (8%) of TV (pneumothorax n=1, skin erosion n=1) and 12/65 (19%, p=0.23) of Epi implants (effusions n=5, heart failure n=1, retained foreign body n=1, pneumothorax n=1, hematoma n=1, disconnection n=1, sepsis n=1, blood loss n=1). Median hospital stay was shorter in TV (2.0 vs 4.5 days, p=0.03). All TV patients and 43 Epi (77%) were anticoagulated. At follow-up, pocket infection occurred in one Epi patient. No clinical thromboembolic event was observed in either group. 3 TV leads failed in 2 patients (9%), while 12 Epi leads failed in 10 patients (18%); however, mean duration of freedom from lead failure was not significantly different (TV 9.9 vs. Epi 8.0 yrs, P=ns). The mean energy threshold was lower at implant for TV leads (0.9 vs 2.2 μJ, P=0.049), but similar for both leads on follow-up (1.2 vs 2.6 μJ, P=0.35). Atrial sensing was unchanged over time for TV (2.2 to 2.0 mV, P=ns), but significantly decreased in Epi (3.4 to 2.4 mV, p=0.006). Conclusions: Transvenous atrial pacing leads may be placed in Fontan patients with lower procedural morbidity than epicardial leads, and equivalent expectation of lead performance and longevity. Although the thromboembolic event rate appears low in anticoagulated patients with both lead types, the present study design cannot fully address this important issue.
Viagra and rationing
Authors: R. Smith
Journal: BMJ (1998)

Editorial p 759 News p 765 Medicine and the media p 824

The inability of Britain's government to come to terms with rationing is exposed by this week's “interim guidance” that doctors should not prescribe sildenafil (Viagra) (pp 000, 000).12 The government should use this opportunity to lead the debate that Britain needs on what will be provided on the NHS, who will decide, and how.

The fiction of the NHS, encouraged by this government and the last, is that the NHS can provide a comprehensive, high quality service that is free at the point of delivery and covers everybody. The reality, well recognised by most of those working in the service, is that health systems cannot meet all four principles.3 Something has to …
Rare sugar d-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus
Authors: Akram Hossain, Fuminori Yamaguchi, Tatsuhiro Matsuo, Ikuko Tsukamoto, Yukiyasu Toyoda, Masahiro Ogawa, Yasuo Nagata, Masaaki Tokuda
Journal: Pharmacology & Therapeutics (2015)
Abstract 12133: Survival in the Elderly Undergoing Cardiac Resynchronization Therapy
Authors: John Rickard, Bryan Baranowski, Dan Sraow, David O Martin, Richard A Grimm, Bruce D Lindsay, Patrick Tchou, Bruce L Wilkoff, Mina K Chung
Journal: Circulation (2010)

Background: Recently, higher in-hospital mortality rates in elderly recipients of biventricular pacemakers and ICDs have questioned the application of device therapy in octogenarians. As elderly pa...
Defective expression and function of p53 in head and neck squamous cell carcinoma cell lines
Authors: Jay Friedman, Zhong Chen, Carter Van Waes
Journal: Cancer Research (2006)

89  TP53 is an important tumor suppressor gene that controls the cell cycle and apoptosis, and regulates the expression of many genes at the transcriptional level. p53 mutations have been observed in approximately 50% of head and neck squamous cell carcinoma (HNSCC), however, the molecular mechanisms of p53 have not been well understood for the cancers with either wild type or mutant p53. In this study, we investigated the expression pattern and function of wild type and mutant p53 in 9 human HNSCC cell lines (UM-SCC) and normal human keratinocytes. Among the 9 UM-SCC cells lines, 4 maintain wild type p53 status and 5 maintain mutant p53 status. cDNA microarray and real-time RT-PCR revealed a lower baseline level of p53 mRNA in cell lines with wild type p53 in comparison to normal keratinocytes. In contrast, there are comparable or higher baseline levels of p53 mRNA in mutant p53 cell lines in comparison to normal keratinocytes. Baseline levels of p53 protein were not detectable in wild type p53 cell lines by Western blot, however, there were higher baseline levels of mutant p53 protein detected in the mutant p53 cell lines when compared with normal keratinocytes. We further examined p53 expression and function under the treatment of cytotoxic agent doxorubicin (Dox). The exposure of normal keratinocytes to a 0.5μg/ml Dox increased p53 mRNA levels, p53 and p21 protein levels, and p53 binding activity. The p53 mRNA levels either remained unchanged or demonstrated a general decrease following Dox treatment in UM-SCC cell lines with either p53 status. No detectable p53 and p21 proteins, or p53 binding activity were observed in cell lines with wild type p53 after treatment. In cell lines with mutant p53, UM-SCC-11B and 38 showed increased levels of p53 and p21 protein, and p53 binding activity after Dox treatment. There was no change in p53 protein levels observed in cell lines 22A, 22B, and 46, and no change in p53 binding activity in 22A and 22B cells, however, cell line 46 showed a decrease in p53 binding activity. p21 protein levels increased in cell lines 22A, 22B, and 46 following Dox treatment. Our data suggest that the defective expression and function of both wild type and mutant p53 could be an important tumorigeneic mechanism in HNSCC cells. The aberrant p53 mRNA expression could contribute to such mechanisms in addition to the regulation at the level of protein degradation and interaction. Research was supported by the Intramural Research Program, NIDCD, project DC-00016
Tuberculin reactions in apparently healthy HIV-seropositive and HIV-seronegative women-Uganda.
Authors: A. Okwera, P. P. Eriki, L. A. Guay, P. Ball, T. M. Daniel
Journal: MMWR Morbidity and Mortality Weekly Report (1990)

In 1988-89 94 postpartum women who had attended Mulago Hospital in Kampala Uganda for uncomplicated pregnancy and have been tested for HIV were tested for tuberculin reactions.  The HIV test was an ELISA kit Recombigen-HIV EIA (Cambridge BioScience Worcester MA).  The tuberculin Mantoux test utilized Old Tuberculin (OT equivalent to 5 units of PPD GT Behringwerke AG Marburg).   33 women were HIV-negative and 61 were HIV-positive.  82% of the seronegative women had positive PPD reactions (>3 mm) with a median diameter of 10.6 mm.  48% of the HIV-negative women had positive PPD tests with a median diameter of 7.5 mm.  56% of the HIV-negative women and 46% of the HIV-positive women had BCG vaccination scars.  For both groups tuberculin non-reactivity was more common in those without a BCG scar.   25% of the HIV-positive and 76% of the HIV-negative women had no reaction to the PPD test.   Not only has the decline in TB cases in the US and in developing countries stopped because of the HIV epidemic but TB mortality has sharply increased.  In central Africa more than half of the adult population has a latent TB infection.  These findings suggest that HIV infection can depress tuberculin reactions before signs and symptoms of AIDS develop.  Prior vaccination with BCG seem to maintain tuberculin reactivity at higher levels than does natural mycobacterial infection.  Thus BCG vaccination complicates the reading of skin testing for TB.
Abstract 16091: Cardioprotective Actions of the N-Terminal-Derived Annexin-A1 Peptide, Ac2-26, Against Myocardial Infarction in vivo
Authors: Rebecca H Ritchie, Chengxue Qin, Renming Li, Jane E Bourke, Helen Kiriazis, Sarah Rosli, Nga Cao, Miles DeBlasio, Yuan Yang, Xiao-Jun Du, Xiaoming Gao
Journal: Circulation (2014)

Myocardial infarction (MI) is the major cause of heart failure and death in the Western world. Annexin-A1 is an endogenous, glucocorticoid-regulated anti-inflammatory protein. We have previously shown that this protein plays an important protective role in preserving left ventricular (LV) viability and function in vitro, actions that are reproduced by treatment with its N-terminal-derived peptide, Ac2-26. Little is known however about its cardioprotective actions in vivo, particularly beyond its early anti-necrotic actions in the first few hours of reperfusion. We now test the hypothesis that exogenous Ac2-26 limits multiple aspects of MI injury, over both the short and longer-term in vivo. In the first study, adult C57BL/6 mice were subjected to ischemia-reperfusion (left arterial descending coronary artery ligation, with 1-7 days reperfusion), and Ac2-26 was administered at 1mg/kg i.v. every 24h commencing 5mins before reperfusion. In the second study, mice were subjected to permanent coronary artery occlusion, with Ac2-26 administered 1mg/kg/day i.p. via osmotic pump inserted at time of surgery. As shown in the Table, Ac2-26 reduced cardiac necrosis after 24h reperfusion (infarct size, plasma troponin I levels), systemic and cardiac inflammation after 48h reperfusion (neutrophil and macrophage infiltration) and cardiac fibrosis after 7 days reperfusion. These protective actions at the level of cardiac morphology were associated with preservation of LV function 4wks after permanent occlusion, as determined on fractional shortening and velocity of circumferential fiber shortening. Taken together, our data is the first evidence of Ac2-26 cardioprotection beyond the first few hours of reperfusion in vivo, and importantly, the first to report Ac2-26-induced preservation of LV function in the heart post MI in vivo.