tbuckley/cabot-search huggingface dataset:
Abstract 5452: O-Linked-n-Acetylglucosamine Formation Reduces Nitric Oxide-Dependent Dilation in Arterioles Exposed to High Glucose Concentrations
Authors: Timea Beleznai, Attila Feher, Ibolya Rutkai, Istvan Edes, Zsolt Bagi
Journal: Circulation (2008)

Hyperglycemia is associated with serious microvascular complications in diabetes mellitus. We hypothesized that under high glucose concentrations, activation of the hexosamine pathway leads to protein O-linked-N-acetylglucosamine (O-GlcNAc) formation which interferes with nitric oxide (NO)-dependent arteriolar dilation. Thus, diameter changes of skeletal muscle arterioles (diameter: ~ 160 μm) isolated from healthy, male Wistar rats were investigated after exposure to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM for 2 hours) concentrations. In arterioles exposed to HG concentration, dilations to histamine were markedly reduced compared to those of under NG condition (max: −6±6% and 69±9%, respectively). Inhibition of NO synthesis with L-NAME reduced histamine-induced dilations in NG arterioles, but it had no effect on microvessels exposed to HG. Dilations to the NO donor, sodium nitroprusside were similar in the two groups of vessels. In the presence of the inhibitor of hexosamine pathway, azaserine histamine-induced dilations were significantly augmented and diminished by additional administration of L-NAME in arterioles exposed to HG concentrations (max: 67±2%). Moreover, under NG condition, exposure of vessels to glucosamine (5 mM, for 2 hours) resulted in reduced histamine-induced arteriolar dilations (max: 26±3%). Upon HG and glucosamine treatment an enhanced O-GlcNAc formation of endothelial NO synthase (eNOS) was detected by Western blots and immunoprecipitation. These findings indicate that high glucose concentration may lead to O-GlcNAc formation of eNOS, which impairs histamine-induced, NO-mediated arteriolar dilations. We propose that interfering with the hexosamine pathway may prevent microvascular complications in diabetes mellitus. On the other hand, our data suggest caveat for glucosamine supplementation to treat osteoarthritis, since it may impair microvascular function.
Abstract P5-06-05: miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer
Authors: Jaime Matta, Clara Isaza, Carmen Ortiz, Erick Suarez, Luisa Morales
Journal: Cancer Research (2015)

Abstract BACKGROUND: MicroRNAs (miRNA) are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 3′-untranslated regions of protein-coding transcripts. Some miRNAs have been used as diagnostic, prognostic and therapeutic markers of breast cancer (BC). It is well established that dysregulation of DNA repair capacity (DRC) is an important risk factor of BC. However, there is little published information as to what specific miRNAs are associated with DRC in women with BC. OBJECTIVE: The main objective of this study was to identify candidate miRNAs associated with dysregulation of DRC in women with BC. METHODS: Plasma samples from 30 BC cases and 30 controls selected based on their DRC levels (low, high) using a proprietary algorithm. Samples were analyzed for miRNA expression utilizing protocols from Applied Biosystems (Life Technologies). The miRNA expression profiling was performed utilizing the RT-PCR TaqMan Array Human MicroRNA A Cards v 2.0 (Applied Biosystems) containing 383 miRNA probes. Single-stranded cDNA was synthesized from 200 ng of total RNA in 8 Multiplex RT primer pool reactions containing stem-looped RT primers that were specific to mature miRNAs. U6 snRNA-001973 was selected for normalization based on our own experimental validations. To quantify the association of the miRNA expression the fold change () was estimated for every detector with the p-values calculated using the t-test. RESULTS: Candidate miRNAs that showed a statistically significant expression were: miR-146, miR-34a, miR-221, Let-7b, miR-193b, miR-132, miR-192, miR-21, miR-197, miR-24, miR-26b, miR-29c were identified based on a false discovery rate of 4%. The results showed that twelve miRNAs differentially expressed in patients with BC. Candidate miRNAs have been reported associated with the expression of twenty seven DNA repair genes. Two of these genes are part of the NER pathway which has been identified by previous studies as important in BC. CONCLUSION: Our preliminary data suggests that differential expression of specific miRNAs might be associated with dysregulation of DRC in BC. The molecular mechanisms by which miRNAs regulate DNA repair genes remain to be elucidated. However, our results lend further promise to the concept of miRNAs as a tool to study the regulation of DRC. We see potentialfuture applications in prognosis and therapy of women with BC. Supported by grants S06 GM008239-20 and 1SCA157250 from the NCI Center to Reduce Health Disparities and NIH-MBRS Program (NIGMS) and NIH-NIGMS #GM082406 (CO). Citation Format: Jaime Matta, Clara Isaza, Carmen Ortiz, Erick Suarez, Luisa Morales. miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-06-05.
Occupational lung disease {middle dot} Introduction: New developments in occupational lung disease
Authors: P S. Burge
Journal: Thorax (1996)

<h3>Abstract</h3> Identifying high-confidence cell-type specific open chromatin regions with coherent regulatory function from single-cell open chromatin data (scATAC-seq) is difficult due to the complexity of resolving cell types given the low coverage of reads per cell. In order to address this problem, we present Semi-Supervised Identification of Populations of cells in scATAC-seq data (SSIPs), a semi-supervised approach that integrates bulk and single-cell data through a generalizable network model featuring two types of nodes. Nodes of the first type represent cells from scATAC-seq with edges between them encoding information about cell similarity. A second set of nodes represents “supervising” datasets connected to cell nodes with edges that encode the similarity between that data and each cell. Via global calculations of network influence, this model allows us to quantify the influence of bulk data on scATAC-seq data and estimate the contributions of scATAC-seq cell populations to signals in bulk data. Using simulated data, we show that SSIPs successfully separates distinct cell types even when they differ in very few mapped scATAC-seq reads, with a significant improvement over unsupervised cell type identification. We apply SSIPs to scATAC-seq data from the developing human brain and show that supervising with just 25 differentially expressed genes from scRNA-seq enables the identification of two subtypes of interneurons not identifiable from scATAC-seq data alone. SSIPs opens the door to identifying high resolution cell types in single-cell open chromatin data, enabling the study of cell-type specific regulatory elements.
Further Observations on the Inhibition of Tumor Growth by Corynebacterium parvum With Cyclophosphamide. II. Effect of Cortisone Acetate 2
Authors: Bernard Fisher, Herbert Rubin, Elizabeth Saffer, Norman Wolmark
Journal: JNCI Journal of the National Cancer Institute (1976)

Studies from this laboratory have demonstrated that the administration of cyclophosphamide (CY) and Corynebacterium parvum (CP) over a prolonged time to C3H mice with established measurable tumors resulted in complete arrest of tumor growth as well as partial and complete regressions in many instances. A study of the effect of two different doses of cortisone acetate (CA), administered two or five times weekly, on the tumor inhibitory properties of this chemoimmunotherapeutic regimen indicated that the addition of a corticosteroid to the CY-CP combination did not alter its tumor-inhibitory properties. There was no significant change when CA was administered with CP; however, tumor inhibition was enhanced to a degree approaching statistical significance when CA was added to CY at dose levels of 1.5 and 2.5 mg twice weekly. These results demonstrated that it may be possible in treatment of humans to administer a steroid in combination with a chemoimmunotherapeutic regimen without inhibition of the regimen's antitumor effects.
Reye's syndrome revisited
Authors: M C.-V. Daele
Journal: BMJ (2002)

Editor—The paper by McGovern et al is based on a non-specific definition and an outdated concept of Reye's syndrome in spite of recent convincing data relating to this issue.1 Reye's syndrome is no longer a specific clinicopathological entity but a descriptive term covering a group of heterogeneous disorders of infectious, metabolic, or toxic aetiology.2

All symptoms in the first case, including the neurological complications, can be explained by the influenza A infection.2 Moreover, the confusion lasting for only 48 hours might have been the result of using antiemetics in a patient who had been vomiting almost hourly for 24 hours.2 Urine toxicology screening does not exclude this additional complication.

In the second case, exhaustive virological investigations and liver biopsy were not performed, and the metabolic screening is incomplete. In both patients the diagnosis of Reye's syndrome is therefore put forward—in the best case—by default.

We are surprised that McGovern et al ignore the misleading biases in the epidemiological studies suggesting a link between Reye's syndrome and aspirin.2,3 The studies were performed on series of children with heterogeneous disorders, which already invalidates their results. In the studies that recorded correctly all drugs given before admission, the use of not one but two drugs was significant—namely, aspirin and antiemetics.2 Neither is the decline of Reye's syndrome an argument for a link with aspirin; evidence shows that this decline is the result of medical progress leading to more correct diagnosis of infectious, metabolic, or toxic disease.2,4

When promoting paracetamol and ibuprofen it would be wise not to conceal their side effects—for example, the hepatotoxicity of paracetamol, which can occur even at minor overdoses given during a few days. This was documented by Rivera-Penera et al and discussed in an accompanying editorial by Heubi and Bien, who assumed that the estimates of the occurrence of paracetamol toxicity are the tip of the iceberg of the total number of cases seen in the United States.5

We end with a question about the five cases seen over 13 years mentioned by McGovern et al in their introduction. Two cases occurred in February 1999, and in both the child had been given aspirin. What had been given to the other children?
459. Immune System Regulation of Transgene Expression in the Brain 1: Systemically Activated Immune Responses Silence Adenoviral Vector-Encoded Transgene Expression in the Brain through Both Non-Cytolytic, and Cytotoxic Mechanisms
Authors: Carlos Barcia, Clare Thomas, Jeff Zirger, Weidong Xiong, Olivier Boyer, David Klatzmann, Maria G. Castro, Pedro R. Lowenstein
Journal: Molecular Therapy (2004)

Top of pageAbstract
First generation adenoviral vectors (RAd) transfer genes into the brain with high efficiency, and provide high levels and long term expression in the absence of priming of an anti-adenoviral immune response. Systemic immunization to the RAd induces a cellular adaptive immune response which eliminates the expression of the transgene from the brain, and causes a chronic inflammatory response. In order to elucidate the mechanisms by which the immune response clears transgene expression from the brain, we asked whether, following the delivery of RAds into the striatum, and systemic immune priming, the immune mediated inhibition of transgene expression: (i) reduces the levels of transgene transcripts, vector genome copy numbers, or both; (ii) was transgene dependent; (iii) was promoter dependent; and (iv) caused brain neurotoxicity. The answer to these questions can indicate the mechanisms by which the adaptive immune response controls transgene expression from viral vectors in the brain. Our experiments provided the following results: (1) Immune-mediated inhibition was transgene independent (both expression of b-gal or HSV1-TK were eliminated); (2) the immune system reduced the levels of mRNA encoding for the transgene by more than 90%, but genome copy numbers were only reduced by 10–20%; (3) activated lymphocytes entering the brain were equally efficient in inhibiting expression from viral murine-CMV, human-CMV, RSV promoters, the neuronal synapsin promoter, and the housekeeping b-actin promoter; (4) localized and statistically significant neurotoxicity was encountered in the substantia nigra, the area of the brain transduced following injection of viral vectors into the striatum. In summary, our data indicate that immune-mediated silencing of RAd-encoded transgene expression in the brain is transgene independent, promoter independent, and acts mainly by reducing the number of mRNA. Importantly, we were able to uncover a localized, but statistically significant reduction in the number of transduced neurons. This strongly suggests that activated lymphocytes exert transgene silencing in the brain through a combination of non-cytolytic, and to a lesser extent, also cytotoxic mechanisms.
Abstract 13263: Long-Term Prognosis and Risk Stratification in Brugada Syndrome: Single Center Experience.
Authors: Hiroaki Tatsumi, Masahiko Takagi, Keiko Maeda, Minoru Yoshiyama
Journal: Circulation (2010)

Background: Risk stratification in Brugada syndrome (BS) has not been fully evaluated. We evaluated long-term prognosis and predictors for cardiac events in clinical, signal-averaged ECG (SAECG) an...
Abstract 201: MED13 Dependent Signaling From The Heart Confers Leanness By Enhancing Metabolism In Adipose Tissue And Liver
Authors: Kedryn K Baskin, Chad E Grueter, Christine M Kusminski, William L Holland, Santhosh Satapati, Shawn C Burgess, Philipp E Scherer, Christopher B Newgard, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2014)

The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously demonstrated that cardiac MED13 modulates systemic energy homeostasis in mice. In the present study, we sought to define the extra-cardiac tissue(s) that respond to cardiac MED13 signaling. Cardiac over-expression of MED13 in mice (MED13cTg) confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression and metabolite levels in heart and liver but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice are metabolically flexible and adapt to fasting. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra-cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues.
Abstract 3913: ATP1A1 overexpression correlates with clinical diagnosis and staging of esophageal cancer: from <i>in vivo</i> to human
Authors: Ming-Tsang Wu
Journal: Cancer Research (2014)

Abstract Purpose: This study aims to identify the novel and potential upregulated genes related to secretionary or membranous proteins for the clinical diagnosis and staging of esophageal squamous cell carcinoma (ESCC). Methods: By combining microarray-based screening, which contained at least 25,000 DNA oligonucleotide probes, of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and 17 human ESCC specimens, we further confirmed the potential candidate genes by tissue arrays in 243 cancer tissues and 126 normal tissues of esophagus from Taiwan, Korea, and USA and by ELISA in 78 serum specimens of ESCC patients from Taiwan. Results: Four candidate genes, including ATP1A1, SPINT2, CMTM8, and AGR2, were chosen due to their up-regulation in more than half of 17 paired tissues from 17 ESCC patients in the microarray-based screening. The four genes were verified by RT-PCR and immunohistochemical (IHC) staining in ESCC tissue specimens and only ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) expression was consistent and further studied. Among the 243 cancer tissues and 126 normal tissues of esophagus, we found that the positive expressions of ATP1A1 by IHC staining were 207 (85%) of 243 in cancer tissues and 88 (70%) of 126 in normal tissues. After adjusted for age and sex, ATP1A1 overexpression had a 3.2-time (95% CI = 1.8-5.6) to be likely in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to the tumor stage by IHC staining. Using the median level of 1,465.0 pg/mL of serum ATP1A1 protein expression as the cut-off point, we found that patients with stage III-IV had a 2.91-fold (1.12-7.36) likely to have high serum ATP1A1 levels than those with stage I-II after adjusting for age and sex. Conclusion: ATP1A1 overexpression may serve as a potential noninvasive marker of the clinical diagnosis and staging for ESCC patients. Note: This abstract was not presented at the meeting. Citation Format: Ming-Tsang Wu. ATP1A1 overexpression correlates with clinical diagnosis and staging of esophageal cancer: from in vivo to human. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3913. doi:10.1158/1538-7445.AM2014-3913
Abstract 13957: Vagal Nerve Stimulation Mitigates Atrial Fibrillation by Attenuating the Intrinsic Cardiac Local Circuit Neuronal Activity
Authors: Siamak Salavatian, Eric Beaumont, Jean-Philippe Longpre, Alan Vinet, Vincent Jacquemet, John A Armour, Jeffrey L Ardell
Journal: Circulation (2014)

Background: Burst electrical stimuli delivered to intra-pericardial mediastinal nerves (MNS) during the atrial refractory period reproducibly evoke atrial fibrillation (AF), an effect dependent upon heterogeneous activation of intrinsic cardiac (IC) neurons. The objective of this study was to determine whether pre-emptive vagus nerve stimulation (VNS) alters MNS-induced neuronal imbalance within the IC neurons thereby impacting susceptibility to AF. Methods: Activities of right atrial ganglionated plexus neurons were identified in anesthetized canines (n=11) using a linear microelectrode array. IC neuron activity was characterized in response to: 1) touch and great vessel occlusion versus (2) stellate ganglion or vagal stimulation. Right MNS was evaluated in relation to evoked IC activity and the potential to induce atrial tachyarrhythmias. Responses were assessed prior to and after pre-emptive left (LCV) or right (RCV) cervical VNS (15 Hz, 500 μs; 1.2x chronotropic threshold; 3 min). Results: In control, 100% MNS sites induced AF. Pre-emptive RCV VNS prevented MNS-induced AF induction from 37% of sites; it shortened AF duration in 56% of sites. Pre-emptive LCV VNS potentiated AF in 46% of right-sided MNS sites, prevented AF in 27% of sites, shortened AF in 7% of sites; it was without effect in 20% of sites. Pre-emptive VNS induced a memory effect of ~40 minutes before the MNS-induced AF returned. VNS effects on IC neuronal responses were related primarily to neurons that responded to both touch/vessel occlusion and efferent activation, as such being defined as local circuit neurons (LCNs). A RCV VNS related decrease in IC LCNs activity (0.61±1.83 to 0.16±0.57 Hz) was correlated with reduction in AF inducibility (p&lt;0.05). Chi-square analysis indicated that an increase in LCN neuronal synchrony during MNS-induced AF was mitigated post VNS (p&lt;0.01). Conclusions: VNS decreases the activity of the IC LCNs while maintaining their stochastic behavior, thereby mitigating AF excitability secondary to local neural imbalances. These anti-arrhythmic effects of VNS exhibit memory. Ipsilateral VNS projections more effectively stabilize discrete IC neuronal networks, likely owing to preferential nerve distributions.
Cyclophosphamide/fludarabine nonmyeloablative allotransplant for acute myeloid leukemia
Authors: Muhammad Rizwan Khawaja, Susan M. Perkins, Jennifer E. Schwartz, Michael J. Robertson, Patrick J. Kiel, Hamid Sayar, Elizabeth A. Cox, Gail H. Vance, Sherif S. Farag, Larry D. Cripe, Robert P. Nelson
Journal: American Journal of Hematology (2014)

We compared survival outcomes following myeloablative allotransplant (MAT) or cyclophosphamide/fludarabine (Cy/Flu) nonmyeloablative allotransplant (NMAT) for 165 patients with acute myelogenous leukemia (AML) in remission or without frank relapse. Patients who received NMAT were more likely to be older and have secondary AML and lower performance status. At a median follow-up of 61 months, median event-free survival and overall survival survival were not different between NMAT and MAT in univariate as well as multivariate analyses. Cy/Flu NMAT may provide similar disease control and survival when compared with MAT in patients with AML in remission or without frank relapse.
Abstract 1446: Isolation of a novel metastasis-related microRNA, miR-518c-5p, induced by the stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer
Authors: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto
Journal: Cancer Research (2014)

Abstract We have demonstrated that stromal-cell derived factor (SDF)-1/CXCR4 system is involved in the metastatic process of oral cancer. Recently, small non coding RNAs, microRNAs (miRNAs) are involved in the metastatic process of several types of cancers. However, the miRNAs contributed to metastases induced by the SDF-1/CXCR4 system in oral cancer are largely unknown. Thus, we examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system, using oral cancer cells, B88-SDF-1 which exhibits functional CXCR4 and distant metastatic potential, in vivo. We examined metastasis-related miRNAs induced by the SDF-1/CXCR4 system using miRNA microarray analysis. Among these miRNAs, we confirmed the upregulation of miR-518c-5p in B88-SDF-1 cells by the real-time PCR analysis. Although LNA-based miR518c-5p inhibitor did not affect the cell growth, but did significantly inhibit the migration of B88-SDF-1 cells. Next, we transfected miR-518c expression vector into parental B88 cells, and isolated stable transfectant, B88-518c. The anchorage dependent and independent growth of B88-518c cells were significantly enhanced in compared with those of mock cells. Moreover, we could detect the enhanced migration of B88-518c cells. LNA-based miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of B88-518c cells, indicating that these phenomenon were dependent on the expression of miR-518c-5p, not on that of miR-518c-3p. Next, we examined the function of miR-518c-5p in vivo. B88-518c cells or mock cells were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with B88-518c cells. These results indicate that SDF-1/CXCR4 system regulates the metastases of oral cancer via induction of miR-518c-5p. Citation Format: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. Isolation of a novel metastasis-related microRNA, miR-518c-5p, induced by the stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1446. doi:10.1158/1538-7445.AM2014-1446