tbuckley/cabot-search huggingface dataset:
On a Wizardless Ward
Authors: Thomas Dorsett
Journal: JAMA (2001)

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Abstract 18577: Skin Autofluorescence is an Independent Predictor of the Coronary Artery Disease
Authors: Yusuke Fujino, Satoko Tahara, Kensuke Takagi, Toru Naganuma, Shotarou Nakamura, Hisaaki Ishiguro, Keiko Fukino, Naoyuki Kurita, Wei Wang, Sunao Nakamura
Journal: Circulation (2014)

Aims: Skin autofluorescence (SAF), a non-invasive measurement of the accumulation for glycation end products (AGEs) level of skin, has been reported as a useful marker for micro/macro vascular complications. However there is little data evaluating whether SAF can be the predictor of the patients with suspected a coronary artery disease (CAD) and indicating the coronary angiogram (CAG). The aim of this study was to evaluate association between SAF and CAD detected by CAG in the catheterization laboratory. Methods: From October/2013-March/2014, 333 patients with suspected the CAD and underwent CAG were enrolled prospectively. SAF were assessed with autofluorescence reader before CAG. Patients with the history of percutaneous coronary intervention, coronary artery bypass grafting were excluded. CAD was defined as if there was at least one coronary artery stenosis greater than or equal to 50% (AHA classification) by CAG. Association between SAF and existence of CAD was evaluated, and we also explored the relationship between SAF and number of diseased coronary artery. Results: Of the 333 patients, CAD was observed in 145 (43.5%) patients. In multivariate logistic regression analysis, age (odds ratio [OR]: 1.03; 95% con[[Unable to Display Character: &amp;#64257;]]dence interval [CI]: 1.00 to 1.06; p = 0.049), gender (male as reference) (odds ratio [OR]: 0.46; 95% con[[Unable to Display Character: &amp;#64257;]]dence interval [CI]: 0.28 to 0.75; p = 0.002), HbA1c (odds ratio [OR]: 1.45; 95% con[[Unable to Display Character: &amp;#64257;]]dence interval [CI]: 1.10 to 1.91; p = 0.008) and SAF (odds ratio [OR]: 4.85; 95% con[[Unable to Display Character: &amp;#64257;]]dence interval [CI]: 2.750 to 8.55; p &lt;0.001) were considered to be the predictors of CAD. Furthermore patients with higher SAF showed more number of coronary artery disease (Figure 1). When we use the response variable greater equal to 2.3 to determine CAD, sensitivity is 0.655 (0.572, 0.732) and specificity is 0.713 (0.642, 0.776). Conclusions: SAF was independent predictor of CAD and showed a possibility of being the surrogate for the CAD as non-invasive methodology.
Combinational analysis of a whole lymph node by OSNA and histology for intra-operative detection of micro-metastases
Authors: Kiyomi Taniyama, Kazuya Kuraoka, Junichi Sakane, Kyoko Makita, Yasumasa Akai, Motonari Daito, Yasuhiro Otomo, Masanobu Shigeta, Tomoya Mizunoe, Yukiyasu Takeuchi, Harumi Tominaga, Masato Koseki
Journal: Clinical Cancer Research (2006)

A47   Recently, GD-100 (SYSMEX, Kobe, Japan) has been released. It rapidly can detect and quantify mRNA by one-step nucleic acid amplification (OSNA). Loop-mediated isothermal amplification (LAMP) is performed and turbidity derived from magnesium pyrophosphate formation with LAMP can be monitored in OSNA. LAMP originally was reported in 2000 as a novel nucleic acid amplification method that uses only one type of enzyme and yields 10 9  of its target in less than an hour. In this study, we compared the sensitivity of OSNA using GD-100 versus conventional real-time RT-PCR, using five colon cancer cell lines. We then applied OSNA to detect micro-metastases in 1) lymph nodes (LNs) from patients with advanced colorectal adenocarcinomas; and 2) LNs submitted for frozen diagnosis from patients with several malignancies. Our goal was to develop a more efficient system to detect LN metastases than histological examination (HE) performed intra-operatively.Methods: CK19 mRNA copy numbers of five colon carcinoma cell lines (Lovo, DLD1, WiDr, Colo201, Colo320) were calculated and compared using OSNA and conventional real-time RT-PCR. Then, 91 LNs submitted for HE from six patients with advanced colorectal adenocarcinomas (ACRAs) and 64 LNs submitted for frozen diagnosis (FD) from 47 patients with several malignancies were examined by means of OSNA and HE.Results: CK19 mRNA copy numbers of all but Colo320 cells detected by OSNA were close to those detected by RT-PCR. The lowest cell counts for Lovo-cells detected by OSNA in one reaction (2 ÂμL) were 0.8 cells. This value corresponds to 1600 carcinoma cells, if the sample lysate is made using 4 ml of homogenizing reagent (HR), since 4 ml HR was used for a 100 to 300 mg LN. Consequently, a 117 Âμm3-tumor mass would be the smallest one detectable by OSNA with GD-100, if a carcinoma cell has a 10-Âμm diameter and the same level of CK19 mRNA copy number as a Lovo cell. On the other hand, either HE+ or OSNA + metastases were detected in 7.9 % of LNs from ACRAs and in 30.0 % of LNs submitted for FD from patients with several malignancies. HE-/OSNA+ metastases were detected in 4.8 % and 4.0 % of these LNs, respectively. Using OSNA, the grade of LN metastasis was increased from n1 to n3 in one patient and from n0 to n3 in another patient with ACRA. OSNA analysis for one LN could be completed within 40 minutes.Summary: Combinational analysis of LN by HE and OSNA may increase the sensitivity of detecting micro-metastases during surgery.
Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster
Authors: Ulrich Mühlenhoff, Sabine Molik, José R. Godoy, Marta A. Uzarska, Nadine Richter, Andreas Seubert, Yan Zhang, JoAnne Stubbe, Fabien Pierrel, Enrique Herrero, Christopher Horst Lillig, Roland Lill
Journal: Cell Metabolism (2014)
Ultrasound and Microbubble-Targeted Delivery of Small Interfering RNA into Primary Endothelial Cells Is More Effective than Delivery of Plasmid DNA
Authors: Lynda J. Juffermans, Bernadet D. Meijering, Robert H. Henning, Leo E. Deelman
Journal: Circulation (2011)

Introduction Ultrasound and microbubble-targeted delivery (UMTD) is a promising non-viral technique for genetic-based therapy. Recently, we demonstrated that with UMTD employing low-intensity ultra...
Abstract 2639: Development of immunocytotoxic RNA therapeutics for human melanoma
Authors: Jaewoo Lee, Youngju Lee, Bruce A. Sullenger
Journal: Cancer Research (2014)

Abstract Pattern recognition receptors (PRRs) are a pivotal component of anti-infectious immunity, and selective induction of PRR-mediated apoptosis in cancer cells represents a novel therapeutic strategy. Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic PRR that recognizes virus-associated molecular patterns, such as uncapped 5′triphosphate (5′ppp) RNA. RIG-I activation triggers innate immune response and apoptosis in infected cells, resulting in the inhibition of viral spread. Interestingly, certain cancer cells are highly sensitive to RIG-I-mediated apoptosis, and treatment with RIG-I-stimulating RNAs can selectively kill cancer cells and facilitate the induction of anti-cancer immunity. Therefore, RIG-I-stimulating RNAs may prove valuable as immunostimulatory and anti-cancer agents. Because RNAs are extremely sensitive to serum nucleases, modified RNAs have been employed to increase the stability of RNA-based therapeutics. Such modifications, however, often abrogate the immunostimulatory activity of RNAs, which hinders their development as immunostimulatory agents. Herein, we demonstrate that short single-stranded RNAs (ssRNAs) (23-93 nucleotides) with 5′ppp and stem-loop structure(s) are a potent stimulus for type I interferon (IFN) production and apoptosis of human melanoma and prostate cancer cells. 2′fluoro (2′F) modification of these 5′ppp ssRNAs not only improves serum stability, but also enhances the ability of the RNAs to induce IFNβ production and apoptosis of human cancer cells, compared to their unmodified counterparts, while 2′ O-methyl modification abrogates the anti-cancer and IFN-inducing activities of 5′ppp ssRNAs. These 5′ppp 2′F ssRNAs elicit RIG-I- and mitochondrial antiviral-signaling protein-mediated IFN production and cytotoxic effects. This study suggests that such modified RNAs may represent a novel and effective anti-cancer therapeutic. Citation Format: Jaewoo Lee, Youngju Lee, Bruce A. Sullenger. Development of immunocytotoxic RNA therapeutics for human melanoma. [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 2639. doi:10.1158/1538-7445.AM2014-2639
Peripheral nervous system involvement in a patient with large T-cell lymphoma arising from a pre-existing mycosis fungoides
Authors: None Peris, None Fargnoli, None Berardelli, None Crecco, None Tomaselli, None Chimenti
Journal: British Journal of Dermatology (1998)

A 29-year-old man was examined for disseminated erythematous scaling patches and plaques and reddish, partially ulcerated nodules. Histological examination showed a dense, diffuse, epidermotropic infiltrate located in the entire dermis to the subcutaneous tissue, composed mainly of large pleomorphic T lymphocytes. Immunohistochemistry revealed positivity of neoplastic cells for T-cell-associated markers, negativity for CD30 antigen and for B-cell markers. Polymerase chain reaction analysis detected a clonal amplification of T-cell receptor gamma. Based on clinicopathological and molecular findings, the diagnosis of large T-cell lymphoma (LCL) arising from a pre-existing mycosis fungoides was made. Seven months after primary diagnosis, meningeal and peripheral nervous system involvement developed with no other evidence of systemic disease. Despite chemotherapy and radiation therapy, the patient died 3 months after the diagnosis of nervous system involvement. In patients with cutaneous LCL, mild neurological symptoms may precede the complete diagnostic picture by some weeks. A rapid and fatal progression characterizes the clinical course of the disease.
Abstract 17436: STAT3 Inhibition Protects Against Cardiomyocyte Hypertrophy Through a Novel NF-kB p65/Nrf2/HO-1 Pathway
Authors: Lei Chen, Lin Zhao, Anweshan Samanta, Kashyap Choksi, Guangming Cheng, Arash Davani, Magdy Girgis, Buddhadeb Dawn
Journal: Circulation (2014)

Introduction: Left ventricular hypertrophy is the end-result of diverse cardiovascular pathologies. STAT3 signaling has been implicated in cardiomyocyte hypertrophy, although the precise mechanism remains incompletely understood. Hypothesis: We hypothesized that STAT3 induces myocyte hypertrophy via NF-kB/Nrf2 pathway. Methods and Results: Treatment of H9c2 cells with 1 μM Angiotensin II for 48 h induced a 2.4-fold increase in cell size compared with controls. This cellular hypertrophy was significantly inhibited in the presence of STAT3 inhibitor WP1066 (Figure). The levels of heme oxygenase-1 (HO-1), a key molecule in cardioprotective signaling, were increased by WP1066 treatment and decreased by STAT3 overexpression. Further investigation of the underlying mechanism revealed that WP1066 blocks the inhibitory effect of NF-kB p65 on Nrf2, leading to an upregulation of HO-1 (Figure). By using chromosome-IP and bioinformatics analysis, we identified that p65 suppresses Nrf2 expression by directly binding to the promoter region of Nrf2. The p65/Nrf2/HO-1 signaling pathway was further confirmed by using both p65 transient overexpression and NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC). Conclusions: We conclude that angiotensin II-induced cardiomyocyte hypertrophy involves STAT3 signaling and downstream components include p65, Nrf2, and HO-1. These novel molecular insights may lead to development of new therapy to prevent and treat cardiac hypertrophy.
How the ‘HAMMER’ can help in effectively treating skin cancer
Authors: W. Hussain, C. Morris, J. Christian
Journal: British Journal of Dermatology (2012)

Journal Article How the 'HAMMER' can help in effectively treating skin cancer Get access W. Hussain, W. Hussain Department of Mohs Micrographic and Reconstructive Surgery Search for other works by this author on: Oxford Academic Google Scholar C. Morris, C. Morris Division of Mohs Histotechnology, Leeds Centre for Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar J. Christian J. Christian Division of Mohs Histotechnology, Leeds Centre for Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 2, 1 August 2012, Pages 454–455, https://doi.org/10.1111/j.1365-2133.2012.10930.x Published: 01 August 2012
Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors
Authors: Craig M. Forester, Sarah E. Sartain, Dongjing Guo, Marian H. Harris, Olga K. Weinberg, Mark D. Fleming, Wendy B. London, David A. Williams, Inga Hofmann
Journal: American Journal of Hematology (2015)

Pediatric acquired aplastic anemia (AA) is a bone marrow disorder that is difficult to distinguish from inherited bone marrow failure syndromes and hypocellular refractory cytopenia of childhood (RCC). Historically, patients with hypocellular RCC have been given the diagnosis of AA. To assess the clinical and histologic distinction between RCC and AA, we performed a retrospective analysis of 149 patients previously diagnosed with AA between 1976 and 2010. We evaluated event free survival (EFS), overall survival (OS), response rates to immunosuppressive therapy, treatment‐related toxicities and clonal evolution. The 5‐year EFS and OS were 50.8% ± 5.5% and 73.1% ± 4.7%, respectively. Patients with very severe AA had worse OS compared to patients with severe and moderately severe AA. Seventy‐two patients had diagnostic pathology specimens available for review. Three pediatric hematopathologists reviewed and reclassified these specimens as AA, RCC or Other based on 2008 WHO Criteria. The concordance between pathologists in the diagnosis of AA or RCC was modest. RCC was associated with a trend toward improved OS and EFS and was not prognostic of immunosuppression therapy treatment failure. There was a low rate of clonal evolution exclusively associated with moderately severe AA. Our findings indicate that a diagnosis of RCC is difficult to establish with certainty and does not predict outcomes, calling into question the reproducibility and clinical significance of the RCC classification and warranting further studies. Am. J. Hematol. 90:320–326, 2015. © 2015 Wiley Periodicals, Inc.
Early G1-phase inhibition of cell cycle progression by Wee1 inhibitor PD0166285 in the B16 mouse melanoma cell line
Authors: Osamu Hahsimoto, Takato Ueno
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1542 

We recently identified the PD2 gene, co-localized on the 19q13 amplicon with AKT2. This gene presents transforming activity when overexpressed in fibroblast cells. The PD2 gene encodes the human RNA polymerase II factor 1 (hPAF1), a member of the PAF1 complex. The PAF1 complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. The PAF1 complex acts as a docking protein in between the complexes Rad6-Bre1, COMPASS-Dot1p, and the phosphorylated carboxyl terminal domain of the RNA polymerase II. As such, PAF1 is directly involved in transcription elongation via histone H2B ubiquitination and histone H3 methylation. Herein, we report that hPAF1 presents a cyclin-like oscillatory expression pattern during the cell-cycle progression. hPAF1 is first detected in the early G1 phase, increases during the S phase, and reaches a maximum level of expression in the G2 phase. Synthesized as a 60 kDa protein, hPAF1 translocates as an 80 kDa protein to the nucleus. In prophase, hPAF1 aligns in filament-like structures, migrates at the pole in metaphase to form a crown surrounding the centrosomes, and is degraded during the metaphase to anaphase transition. We show that hPAF1 delays S-phase entry but favor the G2/M transition. More specifically, hPAF1 positively regulates the transcription of cyclin B1 and Cdk1 and also regulates cyclins A1, A2, D1, and E1. hPAF1 also interacts with both phosphorylated forms of the DNA polymerase α-primase complex, that mediate the replication initiation and elongation mechanisms. Because hPAF1 delays S-phase entry, we hypothesized that hPAF1/DNA polymerase α-primase interaction might limit the DNA polymerase α-primase activity during the replication process. Altogether, hPAF1 and the PAF1 complex appear as potent regulators of the cell-cycle progression, acting as a tumor suppressor. Dysregulation of at least one of the PAF1 members via gene amplification or overexpression leads to the transforming phenotype.
Abstract 19356: Sex-differences in Left Ventricular Mass Changes in Treated Hypertensive Outpatients: The Campania Salute Network
Authors: Costantino Mancusi, Eva Gerdts, Raffaele Izzo, Valentina Trimarco, Marina De Marco, Alfonso Sforza, Mai Tone Lønnebakken, Nicola De Luca, Bruno Trimarco, Giovanni de Simone
Journal: Circulation (2014)

Introduction: In clinical trials, women achieve less regression of hypertensive LV hypertrophy (LVH) than men. Whether this is evident also in less selective hypertensive patients is uncertain. Hypothesis: Find sex-differences in LV mass changes during hypertensive treatment. Methods: We evaluated 6969 hypertensive patients with follow-up&gt;12 months (43% women, 53±11 years) from the Campania Salute Network Registry, during a 4-year median follow up. Clinical and echocardiographic data from baseline and last visit during follow-up were used. Results: At baseline, women were older, had higher systolic blood pressure (BP) and heart rate, lower diastolic BP, Framingham Risk Score and renal function, and included more patients with obesity and LVH (all p&lt;0.001 vs. men). Despite optimal BP control in 62% of patients, LV mass increased over time in the total population, similarly in males and females, whereas relative wall thickness increased only in females (all p&lt;0.0001). Percent change in LVM was positively related to follow-up duration and change in systolic BP, diastolic BP and body mass index (BMI) in both sexes (all p&lt;0.0001). During follow-up, women, but not men, exhibited significant increase in BMI (both p&lt;0.0001). After adjusting for age, follow-up duration, changes in BP and BMI, LV mass increased in the presence of both controlled and uncontrolled BP, but in men the change was less evident when BP was controlled (all p&lt;0.001). In subgroups with baseline LVH (by sex-specific LVM normalized by height2.7), LV mass decreased over time in men, but increased in women (p&lt;0.001). Conclusions: In hypertensive, Caucasian outpatients participating in the Campania Salute Network registry, lack of reduction in LV mass was particularly evident in women, independently of confounders including age, duration of follow-up, changes in BP and BMI, with negligible benefit of BP control on LVH.
Clostridium difficile'nin İnflamatuar Barsak Hastalığı Üzerine Etkisi
Authors: Mazen Issa, Aravind Vijayapal, Mary Beth Graham, Dawn B. Beaulieu, Mary F. Otterson, Sarah Lundeen, Susan Skaros, Lydia R. Weber, Richard A. Komorowski, Josh F. Knox, Jeanne Emmons, Jasmohan S. Bajaj, ve David G. Binion
Journal: Clinical Gastroenterology and Hepatology (2007)
Abstract 14688: TREK-1 Modulates Fibrosis &amp; Diastolic Dysfunction Through Activation of Stress-Activated Kinases
Authors: Dennis M Abraham, Teresa E Lee, Lewis J Watson, Lan Mao, Gurangad Chandok, Matthew J Wolf, Howard A Rockman
Journal: Circulation (2014)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a major public health problem because of its high prevalence and the current lack of effective therapies. HFpEF is thought to develop through diastolic dysfunction caused by diminished ventricular compliance, which is strongly influenced by cardiac fibrosis. Our work identifies TWIK related potassium channel-1 (TREK-1) as a novel modulator of diastolic dysfunction and cardiac fibrosis. Methods &amp; Results: TREK-1 is expressed in mammalian cardiac tissue, although its role in cardiac function is poorly understood. To assess the role of TREK-1 in mammalian cardiac function, we interrogated cardiac function in response to pressure overload in global TREK-1 knockout (KO) mice. TREK-1 KO mice showed normal cardiac function in the basal state. However, TREK-1 KO mice developed exaggerated concentric hypertrophy in response to pressure overload. Despite developing exaggerated hypertrophy, TREK-1 KO mice maintained normal systolic and diastolic function as measured by serial echocardiography and invasive hemodynamics. Invasive hemodynamics showed preservation of ventricular compliance in pressure overloaded TREK-1 KO mice, which was associated with significantly attenuated cardiac fibrosis. The limited fibrosis in the heart was indicative of a general impairment of the fibrotic response as measured by impairments in in vivo cutaneous wound healing and in vitro fibroblast migration assays. To determine the mechanism for how TREK-1 modulates fibrosis, we investigated the activation of signaling pathways in lung fibroblasts harvested from TREK-1 KO mice. In response to the profibrotic ligands TGF beta and TNF alpha, TREK-1 KO fibroblasts showed a significantly attenuated activation of the stress-activated kinases p38 alpha and c-Jun N-terminal kinase (JNK), known mediators of myofibroblast activation. These data suggest a critical role for TREK-1 in fibroblast function via the activation of stress-activated kinases. Conclusions: We identified TREK-1 as being critical to the development of diastolic dysfunction and chamber compliance by modulating the signaling pathways involved in the tissue fibrotic response.