tbuckley/cabot-search huggingface dataset:
Optimized Regulation of Gene Expression Using Artificial Transcription Factors
Authors: Reza Yaghmai, Garry R. Cutting
Journal: Molecular Therapy (2002)

A major focus in the basic science of gene therapy is the study of factors involved in targetspecific regulation of gene expression. Optimization of artificial or “designer” transcription factors capable of specific regulation of target genes is a prerequisite to developing practical applications in human subjects. In this paper, we present a systematic and combinatorial approach to optimize engineered transcription factors using designed zinc-finger proteins fused to transcriptional effector domains derived from the naturally occurring activators (VP16 or P65) or repressor (KRAB) proteins. We also demonstrate effective targeting of artificial transcription factors to regulate gene expression from three different constitutive viral promoters (SV40, CMV, RSV). Achieving a desired level of gene expression from a targeted region depended on several variables, including target site affinities for various DNA-binding domains, the nature of the activator domain, the particular cell type used, and the position of the target site with respect to the core promoter. Hence, several aspects of the artificial transcription factors should be simultaneously evaluated to ensure the optimum level of gene expression from a given target site in a given cell type. Our observations and our optimization approach have substantial implications for designing safe and effective artificial transcription factors for cell-based and therapeutic uses.
Scintigraphic Findings in Gorlin’s Syndrome
Authors: JUSTIN Q. LY
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology and Nuclear Medicine, Wilford Hall Medical Center, San Antonio, Texas Received for publication January 23, 2002. Revision accepted April 17. 2002. Correspondence: Justin Q. Ly, Department of Radiology and Nuclear Medicine, Wilford Hall Medical Center, 2200 Bergquist Drive, Suite 1, Lackland AFB, Texas 78236-5300. E-mail: [email protected]
β1 integrin mediates tamoxifen resistance in breast cancer cells.
Authors: O Pontiggia, E Bal de Kier Joffé, M Simian
Journal: Cancer Research (2009)

Abstract Abstract #1055 Even though it is now well established that the microenvironment plays a central role in modulating tumor progression and response to therapy, its function as a regulator of endocrine resistance in breast cancer has not yet been explored. To do so we have established a bicellular in vitro cell line, called LM05-Mix, from the estrogen dependent M05 mouse mammary tumor (BCRT, in press). The epithelial and fibroblastic cell populations of the LM05-Mix cell line were further separated to generate the LM05-E and LM05-F cell lines respectively, both of which are estrogen receptor (ER) and progesterone receptor positive. We have previously shown that treatment with 10-6M 4-OH-tamoxifen (TAM) induces apoptosis of the LM05-E cells, and that this effect is inhibited when the epithelial cells are co-cultured with the fibroblastic cell population. Immunofluorescence staining to the extracellular matrix component fibronectin (FN) was found to be especially associated to the fibroblastic cells in the co-culture. To investigate whether FN conferred TAM resistance, LM05-E cells and human MCF-7 cells were cultured on recombinant FN and treated for 48 hours with TAM. In both cases FN conferred resistance (P≤0.001). To understand what signaling pathways were involved, the experiments were repeated in the presence of specific inhibitors and both PD98059 and LY294002 reverted the protective effect, implicating the participation of both the MAPK/ERK and PI3K/AKT pathways. Next, to corroborate the activation of these pathways by FN, starved LM05-E cells were treated with FN (30 μg/ml). Phosphorylation of FAK, MAPK/ERK1/2 and AKT was detected by western blot between 3 and 15 minutes of treatment. To find out whether the activation of these pathways by FN could lead to ligand independent activation of the ER and thus account for the induction of TAM resistance, immunofluorescence staining was carried out to serine 118-phosphorylated ER. An increase in the phosphorylation of ER at this site was evident at 15 minutes of treatment both in LM05-E and MCF-7 cells. Finally, to confirm that the protective effect was mediated by the binding of β1 integrin to FN, cells were pre-incubated with either a specific β1 blocking antibody (AIIB2) or mouse IgG and seeded on FN. The protective effect of FN over TAM induced cell death was only reverted in the AIIB2 treated group (P≤0.01). Our results show that FN through its binding to β1 integrin confers TAM resistance and suggest that the mechanism involved would be through the modulation of the activity of ER. Targeting the interaction of breast cancer cells with the microenvironment could be a novel and future alternative for patients with breast cancer whose tumors progress to TAM resistance. This work is supported by a grant from the Susan G. Komen for the Cure Foundation to MS (BCTR0600341). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1055.
ANALYSIS OF FIBRILLATORY WAVES BY FOURIER TRANSFORM SUGGESTS CUT-OFF VALUES FOR DIFFERENTIATING PAROXYSMAL, PERSISTENT, AND CHRONIC ATRIAL FIBRILLATION
Authors: Ira Howard Blau, Hye Jin Hwang, Chung-Keun Lee, Kwang Woo Ahn, Alexis Visotcky, David Ritchie, Mona Lalehzari, Lindsey Krawchuk, Sung Soo Kim, Byung-Il Choi, Moon-Hyoung Lee
Journal: Journal of the American College of Cardiology (2016)
FDG PET/CT Imaging of Extrapulmonary Small Cell Carcinoma of the Adrenal Gland
Authors: Aisheng Dong, Changjing Zuo, Yang Wang
Journal: Clinical Nuclear Medicine (2013)

Extrapulmonary small cell carcinoma (SCC) is an uncommon malignancy. A 57-year-old man was referred because of a 1-month history of left lumbago. MR images showed an ovoid tumor in the left adrenal gland. FDG PET/CT showed intense FDG uptake of the left adrenal tumor with thrombosis of the left renal vein. The patient underwent left adrenalectomy and nephrectomy. Histopathology revealed typical adrenal SCC with neoplastic thrombosis of the left renal vein. This case suggests that FDG PET/CT is useful for staging of extrapulmonary SCC.
AB0386 The Role That ACR Ped-30, 50, 70 Played in Evaluating the Clinical Efficacy of TNF Antagonists in the Treatment of So-Jia
Authors: H. Zeng, P. Zeng, Y. Xie, Y. Tang, M. Wang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Using the ACR Ped-30, 50, 70 to assess the clinical efficacy of tumor necrosis factor antagonist in refractory systemic juvenile idiopathic arthritis (So-JIA). <h3>Methods</h3> Evaluate the 30 refractory SO-JIA patients that achieved TNF antagonists using ACR Ped-30, 50, 70. The evaluation will carry out after treatment of 1 month, 3 months and 6 months. Several indicators will be evulate, insist: (1) the dosage of the hormone; (2) the body temperature; (3) count of active inflammatory joint; (4) blood sedimentation (ESR) or c-reactive protein (CRP); (5) the doctors 9s overall evaluation. If there are at least 3 items that with an improvement between 30% and 49%, it will be regarded that the cases9 30% clinical symptoms alleviate. If there are at least 3 items that with an improvement between 50% and 69%, the cases9 50% clinical symptoms alleviate. If there are at least 3 items that with an improvement above 70%, the cases9 70% clinical symptoms alleviate. It will be treated as poor efficacy or invalid if there are more than 3 items that with an improvement less than 29%. The occurrence of adverse reactions are monitored and recorded at the same time. <h3>Results</h3> After 1 month9s treatment, only 40% (12/30) of children achieved more than 30% of the clinical symptoms alleviated. Among them, 13.3% (4/30) achieved more than 50% of the clinical symptoms alleviated, 10% (3/30) reached more than 70% of the clinical symptoms eased. 2 cases merged with muscular stiffness, so the biological agent9s treatment was stopped. After 3 month9s treatment, 63% (17/27) cases achieved more than 30% of the clinical symptoms alleviated. Among them, 44.4% (12/27) achieved more than 50% of the clinical symptoms alleviated, 22.2% (6/27) reached more than 70% of the clinical symptoms eased 5 cases discontinued because of recurrent infections or the ineffective treatment; 16 cases continued treatment to 6 months Among them, 55.6% (15/27) cases achieved more than 30% clinical symptoms alleviated, 40.7% (11/27) achieved more than 50% clinical symptoms alleviated, 29.6% (8/27) reached more than 70% of the clinical symptoms eased. After 6 month, 3 cases that had more than 70% symptom in remission were recurrent because of repeated infection. 4 cases maintain biological preparation treatment up to two years, 3 of them were in stable condition, and 1 switch to other biological agents because that his bone destruction continued. <h3>Conclusions</h3> The ACR Ped-30, 50, 70 can evaluate the clinical efficacy of tumor necrosis factor antagonists in the treatment of refractory systemic juvenile idiopathic arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5476
The Nitroblue Tetrazolium Reduction Test versus Conventional Hematology in the Diagnosis of Bacterial Infection
Authors: Roy T. Steigbigel, Paul K. Johnson, Jack S. Remington
Journal: New England Journal of Medicine (1974)

Two hundred and eighty-nine patients were prospectively evaluated to determine the value of the nitroblue tetrazolium test as compared to five routine hematologic procedures in diagnosing bacterial infection. Of 529 samples of blood taken for culture, 26 documented bacteremia, and two fungemia. In half the samples showing bacteremia the test was positive (score of ≥ 10), whereas in more than half, the white-cell count was elevated, the differential count revealed increased numbers of immature granulocytes, and toxic granulations were present. In patients with documented bloodstream invasion Döhle bodies and vacuolization were present in 29 per cent. A single hematologic abnormality was present in 93 per cent, and two or more in 79 per cent of the patients with septicemia. The use of conventional hematologic procedures appears to be more sensitive than the nitroblue tetrazolium test in detection of bacterial infection. (N Engl J Med 290:235–238, 1974)
Abstract 1855: Maternal consumption of long chain omega 3 fatty acids decreases risk for mammary gland cancer in the female C(3)1 TAg mouse
Authors: Gabriela Ion, Juliana A. Akinsete, Theodore R. Witte, W. Elaine Hardman
Journal: Cancer Research (2011)

Abstract Omega 3 fatty acids have been shown to reduce incidence and slow growth of mammary gland cancer in rodent models. Omega 3 fatty acids in the maternal diet are important for normal fetal brain, eye and nervous system development. Since exposure to dietary components during the critical developmental times of gestation and lactation may alter risk for mammary gland cancer in females, we tested whether exposure to increased levels of long chain omega 3 fatty acids (from fish oils) would be preventive or promotional to mammary gland cancer in the offspring. Normal SV40 female mice were fed AIN 76 diets containing either 10% corn oil (control) or 5% of an omega 3 fatty acid concentrate + 5% canola oil. Females were then mated with C(3)1 TAg transgenic mice. Transgene hemizygous offspring were the experimental mice not the original SV40 female mice. On a normal diet the hemizygous mice are expected to have about 100% tumor incidence by 150 days of age. At weaning (3 weeks) pups were randomized to either the corn oil or the fish oil diet, 15-17 mice per group. At 140 days of age, mice never exposed to fish oil (C/C group) had a significantly higher incidence and multiplicity of mammary gland tumors than mice exposed to fish oil throughout life (F/F group). Mice exposed to fish oil during a portion of life (C/F or F/C) had intermediate incidences and multiplicities. Interestingly, omega 3 in the maternal diet alone decreased tumor multiplicity by 50% compared to no omega 3, even when the mouse received a control diet after weaning. If a mouse, developed a tumor the mean tumor masses were not significantly different though the F/F group had a much smaller mean tumor mass. Adequate omega 3 fatty acids in the maternal diet may reduce risk for mammary gland cancer in the offspring. 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 1855. doi:10.1158/1538-7445.AM2011-1855
P392Ryanodine receptor cluster organisation and consequences for EC coupling
Authors: MB Cannell, CHT Kong, DR Laver
Journal: Cardiovascular Research (2014)

The organization of sarcoplasmic reticulum release channels (ryanodine receptors -RyRs) in to clusters in dyads is a critical structure for cardiac excitation contraction coupling. Until recently the organisation of the RyRs was known only from electron micrographs (EMs), however the development of optical super resolution techniques has allowed identification of RyRs from antibody labelling experiments and the RyRs form complex structures with fewer RyRs than inferred from most thin section EMs. This has important implications for understanding the both the flux from the SR as well as possible local SR depletion during EC coupling. Furthermore, experiments in which a fraction (∼30%) of the RyRs are blocked in each dyad changes the behaviour of Ca sparks with longer lasting release events (>200 ms) becoming more common. Recently we showed that termination of regenerative Ca release from RyRs can be produced by the interaction of RyR closed time with the decaying local Ca concentration due to local SR depletion and this ‘induction decay’ mechanism appears to be robust giving reliable termination. Both induction decay and stochastic attrition mechanisms do not, by themselves, predict the long lasting events seen in he presence of tetracaine. However, if SR Ca load is increased the increased, long lasting Ca release events can develop as the release flux and local dyad Ca can be sustained by junctional SR being replenished by diffusion from the SR network. In this case, the release by the reduced number of RyR can be analysed by stationary noise analysis. Using this approach, we were able to detect excess low frequency noise which was described by a single Lorentzian component. Assuming that each open RyR produces a miniature spark-like event and applying Campbell's theorem, these data are consistent with the elementary event having an amplitude of 0.073 ± 0.022 F/Fo units which is below the detection limit of published Ca spark detection algorithms. Importantly, these elementary events are consistent with estimates of the single RyR current and suggest that ∼30 RyRs gate in concert to produce a normal Ca spark. These data suggest that observations of occasional 'quarky' Ca release release may not be due to a single RyR channel gating but rather premature failure of regenerative CICR with a RyR cluster. Our estimate of the number of RyRs in a cluster from noise analysis of tetracaine-modified Ca sparks is consistent with super resolution measurements of peripheral RyR clusters after accounting for the different geometry associated with peripheral and central RyR clusters and Ca sparks.
OP0240 Higher Expression of TNFR1 and IL-1R2 on Cell Surface of B*2705 Ankylosing Spondylitis Patients Vs B*2705 and B*2709 Healthy Subjects. Influence of Erap1 Polymorphism
Authors: A. Cauli, G. Dessole, G. Porru, A. Cassotta, M. Piga, A. Vacca, V. Ibba, P. Garau, M. T. Fiorillo, R. Sorrentino, A. Mathieu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles, with the exception of B*2706 and B*2709. GWAS studies have revealed that other genes are also involved in AS pathogenesis such as ERAP1 which is able to cleave TNFR1 and IL-1R2 cell surface receptors, supposed to play a pivotal role in AS pathogenesis. <h3>Objectives</h3> To analyze the cell surface expression of TNFR1 and IL-1R2 receptors and the possible influence of ERAP1 allelic variance. <h3>Methods</h3> The percentage of CD14 negative peripheral blood mononuclear cells (PBMC) expressing TNFR1 and IL-1R2 receptors on the cell surface was evaluated in 12 HLA-B*2705 patients with AS, 12 HLA-B*2705 healthy subjects (HC) and 12 HLA-B*2709 HC by means of flow cytometry analysis and CD120a and CD121b monoclonal antibodies, respectively. Patients and controls were genotyped for two ERAP1 SNPs associated with AS (rs27044 C/G and rs30187 C/T). Values were expressed as median percentage of positive cells (interquartile range). The differences between AS patients and HC were analyzed by Mann Whitney U-test. <h3>Results</h3> TNFR1 expression on PBMC was significantly higher in AS patients (35.5 IQR 15.9-60.4) compared to B*2705 HC (18.9 IQR 9.7-25.5, p=0.04) and B*2709 HC (13.1 IQR 9.3-21.5, p=0.02). IL-1R2 was also significantly higher in AS patients (1.5 IQR 0.6-2.5) compared to B*2705 HC (0.2 IQR 0.1-0.8, p=0.01) and B*2709 HC (0.6 IQR 0.1-1.6, p=ns). The majority of AS patients and HC were heterozygous both for rs27044 (C/G) and rs30187 (C/T); the higher numbers of TNFR1 and IL-1R2 positive cells found in AS patients compared to HC were not due to differences in the ERAP1 allelic distribution in patients and controls as shown in the figure below: <h3>Image/graph</h3> <h3>Conclusions</h3> This study shows a higher expression of TNFR1 and IL-1R2 on the PBMC surface of AS patients compared to B*2705 and B*2709 regardless of ERAP1 allelic variance, underlining the important role of these two cytokines in the pathogenesis of AS. <h3>Disclosure of Interest</h3> None Declared
Abstract SY13-01: Noncoding RNAs: From bench to bedside
Authors: George A. Calin
Journal: Cancer Research (2011)

Abstract The newly discovered differential expression in numerous tissues, key cellular processes and multiple diseases for several families of long and short noncoding RNAs (ncRNAs, genes that do not codify for proteins but for RNAs with regulatory functions), including the already famous class of microRNAs (miRNAs) strongly suggest that the scientific and medical communities have significantly underestimated the spectrum of ncRNAs whose altered expression has significant consequences in diseases. MicroRNA and other short or long noncoding RNAs alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of noncoding RNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long noncoding RNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify noncoding RNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of noncoding RNAs participate in the genetic puzzle giving rise to the malignant phenotype. Last, but not least, the shown expression correlations of these new ncRNAs with cancer metastatic potential and overall survival rates suggest that at least some member of these novel classes of molecules could potentially find use as biomarkers or novel therapeutics in cancers and other diseases. 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 SY13-01. doi:10.1158/1538-7445.AM2011-SY13-01
Esthesioneuroblastoma (Olfactory Neuroblastoma) Treated With 111In-Octreotide and 177Lu-DOTATATE PRRT
Authors: William Makis, Karey McCann, Alexander J.B. McEwan
Journal: Clinical Nuclear Medicine (2015)

A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma.
Case 15-1998
Authors: Generoso G. Gascon, Matthew P. Frosch
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 34-year-old right-handed woman was admitted to the hospital because of progressive confusion and visual loss.The patient had been well until four months earlier, when her family observed a reduction in spontaneous speech, increasing timidity, and confusion during her fourth pregnancy. Two months before admission she was unable to sign checks reliably, although it was unclear whether the problem was related to her vision or confusion. She began to report a persistent right frontal headache. Three weeks before admission, she had an uncomplicated vaginal delivery at another hospital. Two days later, she could not sign her . . .
Exacerbation of Autoimmune Thyroid Dysfunction after Unilateral Adrenalectomy in Patients with Cushing's Syndrome Due to an Adrenocortical Adenoma
Authors: Nobuyuki Takasu, Ichiro Komiya, Yoshitaka Nagasawa, Takayuki Asawa, Takashi Yamada
Journal: New England Journal of Medicine (1990)

Little is known about the factors that cause exacerbations of autoimmune thyroid dysfunction. One possibility is an alteration in adrenocortical function, since glucocorticoids are known to alter both pituitary-thyroid and immunologic function. We encountered three patients in whom overt autoimmune thyroid disease developed after unilateral adrenalectomy for Cushing's syndrome due to an adrenocortical adenoma. We compared the postoperative changes in thyroid function in these patients with those in 21 other patients with Cushing's syndrome who underwent the same treatment. After unilateral adrenalectomy, one of the three patients had transient hyperthyroidism and a low thyroid uptake of 131I, indicative of silent thyroiditis. After the same surgical procedure, the second patient had hypothyroidism, where-as the third patient had transient hyperthyroidism at first, and hypothyroidism then gradually developed. All three patients had serum antithyroid antibodies, the titers of which increased after surgery. In the remaining 21 patients (only 2 of whom had antithyroid antibodies initially), the serum concentrations of thyroxine, triiodothyronine, and thyroxine-binding globulin and the secretion of thyroid-stimulating hormone increased after surgery from values that were low or near the lower limit of normal to values still well within the normal range. None of these patients had clinically evident thyroid disease or increased antithyroid-antibody titers. We conclude that reductions in the secretion of glucocorticoid may exacerbate subclinical autoimmune thyroid disease. Patients with Cushing's syndrome due to adrenocortical adenoma who have thyroid antibodies should be followed closely after treatment, because thyroid dysfunction may develop.