tbuckley/cabot-search huggingface dataset:
HG-04 * NEURONAL ACTIVITY-REGULATED SECRETION OF NEUROLIGIN-3 PROMOTES GLIOMA GROWTH
Authors: H. Venkatesh, T. Johung, V. Caretti, A. Noll, H. Vogel, M. Bredel, P. Mallick, M. Monje
Journal: Neuro-Oncology (2015)

Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins for high-grade glioma (HGG). We demonstrate that active neurons similarly promote HGG proliferation and growth in vivo using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma orthotopic xenograft model. Activity-regulated mitogen(s) are secreted, as the conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures. The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen; soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feed-forward expression of NLGN3 in glioma cells, providing mechanistic insight into its surprising role as a mitogen. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted neuroligin-3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth.
Renal Artery Stenosis Secondary to Takayasu's Arteritis Demonstrated on Tc-99m MAG3 Renal Scan
Authors: CHARLES M. CALDWELL, DEAN J. SHANLEY, EVERETT L. GAYLE
Journal: Clinical Nuclear Medicine (1996)

Renovascular hypertension is much more common in the pediatric population compared to adults and is usually secondary to fibromuscular dysplasia. Other renal related causes of hypertension in children include vasculitis, chronic pyelonephritis, hydronephrosis, chronic pyelonephritis, and trauma. Takayasu's arteritis, an uncommon vasculitis involving primarily the aorta and its major branches, can result in renal artery stenosis and hypertension in young patients. The authors present a case of renal artery stenosis secondary to Takayasu's arteritis demonstrated on renal scintigraphy. Correlation with conventional angiography provided additional information about the extent of involvement of the renal arteries and abdominal aorta.
In-111 Octreotide Lung Uptake in Hypersensitive Pneumonitis Caused by Fungal Infection
Authors: J D Slavin, R M Sherigar, R P Spencer, M N Lassman
Journal: Clinical Nuclear Medicine (1998)

Results of a chest radiograph taken in a 60-year-old woman with evidence of adrenal hyperfunction were within normal limits. In an effort to localize abnormal adrenal tissue, an In-111 octreotide study was done. Marked uptake was seen in both lung fields, on images obtained 6, 24, and 48 hours after administration. Lung biopsy showed changes that were consistent with a hypersensitivity reaction. Stains for fungi showed spherical bodies 7 to 12 μm in diameter. There was clearing of an area surrounding each fungal capsule, suggesting an external coat. The patient's concentration of In-111 octreotide in the lungs was likely related to a hypersensitive reaction to the fungi.
Abstract P5-01-03: Discordant Estrogen and Progesterone Receptor Status in Breast Cancer
Authors: MM Hefti, R Hu, N Knoblauch, L Collins, RM Tamimi, AH Beck
Journal: Cancer Research (2012)

Abstract Introduction: Hormone receptor status is used to guide clinical therapy in breast cancer. Estrogen receptor (ER) assays from pathology reports have been shown to be in agreement with ER measured by a centralized laboratory on tissue microarray 87% of the time (Kappa = 0.64); however, little is known of reproducibility within subsets of patients defined by ER/PR status (1). Methods: We computed percent agreement and Kappa statistics for ER/PR status as reported in pathology reports from Nurse's Health Study (NHS) participants with breast cancer from 1976 to 2000, and as scored by immunohistochemistry (IHC) on tissue microarrays at a central laboratory (n = 2011). Statistics were computed separately for 4 subsets of patients stratified by ER/PR status as defined by pathology reports (ER+/PR+, ER+/PR−, ER−/PR+, ER−/PR−). We also used a curated compilation of publicly available gene expression data sets providing both IHC and microarray data on ER and PR expression (n = 1236). Results: We observed significant heterogeneity in Kappa values across the four groups of patients, with ER+/PR+ and ER−/PR- showing the strongest agreement, ER+/PR- showing fair agreement, and ER−/PR+ showing no significant agreement: 89.1% of ER+/PR+ cases from medical record were ER+/PR+ by TMA (κ=.60), 69.4% of ER−/PR- cases from medical record were ER−/PR- by TMA (κ=.63), 42% of ER+/PR- cases from medical record were ER+/PR- by TMA (κ=.37), and only 6% of cases of ER−/PR+ cases from medical record were ER−/PR+ by TMA (κ=.06). Using publicly available microarray data, we observed similar results comparing IHC to gene expression data in the same samples. Expression values were scaled across patients, and a patient was classified as positive for the marker by microarray if the scaled expression value was greater than zero. The agreement between IHC data and gene expression-based classification was 50.0% (k = .50), 80.8% (κ=.54), 42.0% (κ=.15), and 7.2% (κ = −.006) for ER+/PR+, ER−/PR−, ER+/PR−, and ER−/PR+, respectively. Conclusion: ER−/PR+ is by far the most rare and least reproducible subset of breast cancer cases. Given the lack of reproducibility of the ER−/PR+ group and the minimal reported benefit from hormonal therapy in these patients (2), these data question the clinical utility of assessment of PR, particularly in ER− breast cancer. 1. Collins LC, Marotti JD, Baer HJ, Tamimi RM. Comparison of estrogen receptor results from pathology reports with results from central laboratory testing. Journal of the National Cancer Institute. 2008;100(3):218–21. 2. Anderson H, Hills M, Zabaglo L, A'Hern R, Leary AF, Haynes BP, et al. Relationship between estrogen receptor, progesterone receptor, HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO. 2011;22(8):1770–6. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-03.
RISK SCORES AND BIOMARKERS FOR THE PREDICTION OF 1-YEAR OUTCOME AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Jan-Malte Sinning, Kai Wollert, Alexander Sedaghat, Christian Widera, Marie-Caroline Rademacher, Claire Descoups, Christoph Hammerstingl, Marcel Weber, Anja Stundl, Alexander Ghanem, Julian Widder, Mariuca Vasa-Nicotera, Fritz Mellert, Wolfgang Schiller, Johann Bauersachs, Berndt Zur, Stefan Holdenrieder, Armin Welz, Eberhard Grube, Michael Pencina, Georg Nickenig, Nikos Werner, Tibor Kempf
Journal: Journal of the American College of Cardiology (2015)
Overcoming tumor resistance to cisplatin by cationic lipid-assisted prodrug nanoparticles
Authors: Zhi-Ting Cao, Zhi-Yao Chen, Chun-Yang Sun, Hong-Jun Li, Hong-Xia Wang, Qin-Qin Cheng, Zu-Qi Zuo, Ji-Long Wang, Yang-Zhong Liu, Yu-Cai Wang, Jun Wang
Journal: Biomaterials (2016)
US taskforce will push for parity in mental health and substance misuse treatment
Authors: Michael McCarthy
Journal: BMJ (2016)

The US president, Barack Obama, has ordered the creation of a federal taskforce to ensure that health insurers’ coverage of mental health and substance misuse disorders is comparable to their coverage of medical and surgical services.

This latest initiative in Obama’s bid to combat a growing epidemic of opioid misuse in the United States was unveiled at the National Prescription Drug Abuse and Heroin Summit in Atlanta, Georgia. Obama said that, while his administration would continue its efforts to block …
Endoscopic treatment of a duodenal duplication cyst
Authors: Reuben Kurien, Sudipta Chowdhury, L. Unnikrishnan, Ebby Simon, Amit Dutta, Koyeli Mahanta, Thomas Alex, A. Joseph
Journal: Endoscopy (2014)

A young lady presented to the emergency department with pain in the abdomen for 1 day. She had a history of similar pain in the past. Her clinical examination was unremarkable, except for mild abdominal tenderness. Further investigations suggested diagnoses of acute pancreatitis and a duodenal cyst. Magnetic resonance cholangiopancreatography (MRCP) revealed a cystic lesion in the duodenum in close proximity to the common bile duct (CBD) and the main pancreatic duct (MPD) ([Fig. 1] and [Fig. 2]). The patient improved with supportive care.
P126The role of MIP1 in cardiac myocyte hypertrophy and survival
Authors: C Mansfield, B Buyandelger, S Kostin, G Knoell, MR Toliat, A Perrot, W Haverkamp, H Milting, P Nurnberg, R Knoell
Journal: Cardiovascular Research (2014)

Purpose: Mutations in several sarcomeric Z-disc proteins, such as muscle LIM protein (MLP), have been shown to cause hypertrophic and dilated cardiomyopathies. The transcription factor MIP1 has been identified as a novel MLP interacting protein which is important in the cardiac stress response and able to cause cardiac hypertrophy in vivo. Here we examine, in vitro, the mechanisms behind this cardiac phenotype and investigate potential disease causing mutations in this protein.

Methods and Results: Adenoviral overexpression of MIP1 in adult and neonatal rat cardiomyocytes (NRCMs) showed that MIP1 induces cardiac myocyte hypertrophy, as seen by increased cell size and real-time impedance measurements (n=10, p<0.01). MIP1-induced hypertrophy was significantly reduced by calcineurin inhibition by cyclosporine A (0.2μM; n=4, p<0.05). We also analyzed apoptotic events and impedance measurements after doxorubicin (1μM) treatment and found that MIP1 overexpression protects from apoptosis (n=7, p<0.05).

A recent large Genome-wide Association Study suggested a role for genetic variation of MIP1 in disease susceptibility. We sequenced the human MIP1 gene in 916 unrelated individuals affected by cardiomyopathy and heart failure and identified three novel heterozygous variants (G179S, A188V, Q531R) and one that had been described previously (T106M). Adenoviral expression of all four mutants resulted in hypertrophy of NRCMs (n=5, p<0.01) and the mutant proteins were shown to be mislocalised in a proportion of adult cardiac myocytes (G179S 14.6%, A188V 22.6%, Q531R 25.7%) or not stably expressed (T106M). Hypertrophy induced by mutant MIP1 expression was not affected by calcineurin inhibition, indicating a different mechanism, and mutant MIP1 is not as efficient as the wild-type protein at protecting against doxorubicin-induced apoptosis (n=5, WT vs. -T106M p<0.05, -G179S p<0.05, -A188V p<0.01, -Q531R p<0.05).

Conclusions: MIP1 regulates cardiac hypertrophy and cell survival, a recognized dual-property of genes of central importance for cardiac myocyte biology. The effects of MIP1 are dependent on calcineurin and mutations in MIP1 may be a potential cause of hypertrophic cardiomyopathy and heart failure.
FRI0060 Carotid Doppler Assessment of Ambulatory Rheumatoid Arthritis Patients with and without Periodontitis
Authors: J.P. Vinicki, F. Cintora, A. Saad, O. Fernandez, L. Nicolosi, S. Berensztein, G. Nasswetter
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Carotid atherosclerosis is one of its manifestations and can be assessed noninvasively by ultrasound. Systemic inflammation is a risk factor for developing ACVD. Rheumatoid arthritis (RA) and periodontitis (PO) are associated with the development of systemic inflammation and ACVD, however the role of the PO is controversial as potential confounders such as smoking and diabetes are independent risk factors for both PO to ACVD. <h3>Objectives</h3> To evaluate whether moderate or severe PO is independently associated with the presence of carotid atherosclerotic disease in patients with RA. <h3>Methods</h3> An observational, cross-section study was performed. Patients diagnosed with RA (ACR/EULAR 2010) in ambulatory monitoring were included. We excluded those with known cardiovascular disease (heart attack, stroke, heart failure and valvular disease). All participants underwent a clinical evaluation, laboratory tests, dental evaluation and carotid Doppler ultrasound (measurement of intima-media thickness and detection of atheromatous plaques) according to the recommendations of the American Heart Association. The population was divided into 2 groups (G1: with moderate or severe PO and G2: no PO or mild PO). For the analysis of categorical variables, Chi 2 was used (or Fisher exact correction as necessary) and for continuous variables Student test was applied. In all cases a P value less than 0.05 was considered significant. Multivariate analysis was performed using logistic or linear regression as was applicable for adjusting for sex, age, smoking, and diabetes, among other variables. <h3>Results</h3> Seventy two patients with RA were included, mean age 54.8 (±3.6) years, 93.9% female, median time from diagnosis of RA 10.7 (±9.2) years. Thirty-one patients (43.1%) had PO. Fifteen patients (20.8%) belonged to the G2. G2 patients had a trend to older age but did not reach statistical significance (60.7±10.2 vs 53.2±14.3, P=0.054) and higher prevalence of males (20% vs 0%, P&lt;0.001). No statistically significant differences in the prevalence of other risk factors, anthropometric measurements and blood pressure were evident. Table 1 shows the main findings in univariate analysis. G2 patients had a higher prevalence of bilateral carotid plaque and increased maximum EIM. When multivariate analysis adjusting for age, sex, smoking and diabetes were conducted no significant differences between groups for the presence of plaques and intima-media thickness showed up. <h3>Conclusions</h3> In this cohort of patients with rheumatoid arthritis, the presence of moderate or severe periodontitis was not associated with the presence of carotid atheromatous lesions. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6065
Significance of the Visualization of Bone Marrow During Dipyridamole Tc-99m Tetrofosmin Myocardial and Gated SPECT
Authors: Wei-Jen Shih, Chin-Yang Li, Vickie Kiefer
Journal: Clinical Nuclear Medicine (2002)

From the Nuclear Medicine Service,* Lexington VA Medical Center, and Department of Diagnostic Radiology,† School of Medicine, University of Kentucky, Lexington, Kentucky; and the Division of Hemapathology,‡ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Received for publication December 12, 2001. Revision accepted February 28, 2002. Correspondence: Wei-Jen Shih, Nuclear Medicine Service, Lexington VA Medical Center, 1101 Veterans Drive, Lexington, Kentucky 40502-2236. E-mail: [email protected]
FRI0587-HPR Symptomatic hand oa is related to higher body mass index (BMI) early in life, and lower bmi later in life. results from a 20 year population based prospective cohort study.
Authors: K. Magnusson, P. Mowinckel, I. K. Haugen, K. B. Hagen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Obesity is a known risk factor for knee OA and to a lesser extent for hip OA. There is moderate evidence that obesity is a risk factor for radiographic hand OA. Whether high BMI may be a risk factor for symptomatic hand OA, and whether BMI over time is different for persons with hand OA compared to healthy, is to our knowledge, unknown. <h3>Objectives</h3> The aim of this prospective cohort study was to investigate whether BMI is a risk factor for hand OA. <h3>Methods</h3> The project is a part of the "Musculoskeletal pain in Ullensaker Study" (MUSt). Participants aged 20-59 years in 1990 received postal questionnaires in 1990, 1994, 2004 and 2010 (N=1039). Persons with self-reported knee, hip and/or hand OA in 2010 were invited to participate at a clinical examination. On the basis of a clinical evaluation by a physician, a classification of hand OA was made according to the ACR-criteria (N=59). BMI was calculated based on self-reported height and weight at the four different measurement times. BMI over time for the persons with hand OA was compared to the BMI over time for the persons with no self-reported OA (N=980), with the use of a Generalized Estimating Equation analysis, adjusted for age, sex and education level (primary/upper secondary school vs. &gt;1 year college/university). <h3>Results</h3> The mean age was 37 (10.4) years of age in 1990 and 54% were females. Persons who were diagnosed with hand OA in 2010 had higher BMI in 1990 than persons who were not diagnosed (B, 1.12, 95% CI, 0.16 to 2.07). Although BMI increased consistently for the whole cohort the next 20 years (B, 0.92, 95% CI, 0.84 to 0.99 for 1 unit = 6.7 years increase), there was a significant interaction between OA status and time (p=0.007). In 1994, 2004 and 2010, persons with hand OA had lower BMI than those without, and the difference between groups increased for each year (B, -0.09, 95% CI, -0.64 to 0.45 in 1994: B, -3.12, 95% CI, -5.12 to -1.13 in 2004: B, -4.94, 95% CI, -7.97 to -1.92 in 2010). These differences could not be explained by age at baseline. Sex was a confounder of the relationship (for females: B, -1.28, 95% CI, -1.70 to -0.85) but education had no influence on the estimates and was taken out of the model. <h3>Conclusions</h3> Having symptomatic hand OA was related to higher BMI early in life, and lower BMI later in life, as compared to healthy, independent of age and education level. The study indicates that the relationship between BMI and hand OA is complex. However, high BMI related to poor lifestyle was relatively uncommon in Norway at the two first measurement points, which may indicate that heredity may play a greater role for high BMI and hand OA than the role of later lifestyle-related BMI alone. <h3>Disclosure of Interest</h3> None Declared
Abstract 5072: Genome sequencing of metastatic colorectal carcinomas to identify potential targets for therapy in patients
Authors: Viji Shanmugam, Ramesh K. Ramanathan, Shripad Sinari, Manpreet Chadha, Winnie Liang, Ahmet Kurdoglu, Tyler Izatt, Alexis Christoforides, Hollie Benson, Lori Phillips, Angela Baker, Galen Hostetter, Daniel D. Von Hoff, David Craig, John Carpten
Journal: Cancer Research (2012)

Abstract Colorectal carcinoma is one of the most common cancers in the western world, being the third most common cause of cancer-related morbidity and mortality. The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy, especially with a Kras mutation is poor with median survival of less than one year. The purpose of this study was to identify therapeutically actionable somatic events in mCRC patient samples, so as to obtain select targeted treatment strategies for individual patients. Fresh frozen needle biopsies of liver metastases were collected from three mCRC patients along with whole blood for the extraction of constitutional DNA. All patients had greater than 2 prior regimens and had known K-ras mutations. Whole genome sequencing was performed using Illumina paired-end chemistry on HiSeq2000 sequencing system, which yielded coverage of greater than 30X for both the normal and tumor samples. Somatic genomic alterations (point mutations and indels, copy number alterations, translocations and rearrangements) were analyzed using our custom pipeline for paired analysis. We found that all 3 tumor samples had KRAS mutations, while 2 samples had mutations in the APC gene and the PIK3CA gene. Other genes with therapeutic implications in single tumor samples were INPPL1, INPP4B and SMAD4. No EGFR amplifications were detected in our sample set. Pathway analysis revealed K-RAS regulation and apoptosis and survival pathways in these tumor samples. Analysis of paired-end data from these three tumors did not reveal the presence of translocations at the recently discovered TCF7L2 locus (Bass et al, Nature Genetics, 2011). The concomitant mutations in MAPK (KRAS) and PI3K (PIK3CA, INPPL1, INPP4B) pathways suggest that combination therapies might be required for effective treatment of these tumors. By harnessing the power of Next-Gen Sequencing, our study has revealed a series of therapeutically actionable events in mCRC that might provide insights into treating these difficult to treat advanced tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5072. doi:1538-7445.AM2012-5072
Abstract 467: Circulating DNA released from brain tumors in response to conditional cytotoxic/immune stimulatory gene therapy induces activation of TLR9 on pDCs, leading to antitumor immunity
Authors: MARIANELA CANDOLFI, Kader Yagiz, Karthika Balasubramanian, Mariana Puntel, Gwendalyn D. King, Yohei Mineharu, AKM G. Muhammad, David Foulad, Nicholas Barnett, Kurt M. Kroeger, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2011)

Abstract Complexes of DNA and proinflammatory proteins are found in serum during autoimmune responses and activate antigen presenting cells, contributing to autoimmune pathogenesis. Although circulating DNA has been extensively evaluated as a biomarker for cancer progression, its role in the onset of anti-tumor immunity remains elusive. Here we aimed to evaluate the role of circulating DNA in the induction of anti-tumor immunity induced by the combination of immune-stimulant Flt3L and conditionally cytotoxic thymidine kinase (TK), which leads to long-term survival when delivered into intracranial brain tumor models using adenoviral vectors (Ad). Treatment of CNS-1 glioblastoma cells with Ad.TK+GCV led to substantial release of DNA in vitro. Similar results were observed in vivo; intratumoral treatment of established intracranial CNS-1 glioblastomas in rats with Ad-TK/GCV+Ad-Flt3L led to increased levels of circulating DNA in serum when compared to saline-treated tumor-bearing rats. Since our previous results suggest that tumor immunity was dependent on the function of activated pDCs, we aimed to evaluate the hypothesis that circulating tumor DNA induces pDC activation. Using specific inhibitors, such as DNAse, micrococcal DNAse, CpG2088 (an inhibitor of TLR9) and cloroquine (an inhibitor of endocytosis, required for intracellular TLR9 activation), we found that circulating DNA from treated rats induced TLR9-dependent activation of pDCs. Taken together, our results suggest that after treatment of brain tumors with Ad.TK+Ad.Flt3L dying tumor cells release DNA to the general circulation, which mediate antitumor immunity by acting as danger-associated molecular patterns, leading to TLR9 signaling and pDC activation. Supported by NIH/NINDS grants Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 467. doi:10.1158/1538-7445.AM2011-467