tbuckley/cabot-search huggingface dataset:
Abstract 2791: SINE retrotransposons cause epigenetic reprogramming of adjacent gene promoters
Authors: Marcos R.H Estecio, Mhair Dekmezian, Juan Gallegos, Shoudan Liang, Jean-Pierre Issa
Journal: Cancer Research (2011)

Abstract Retrotransposons of SINE and LINE classes have been extremely successful in colonizing mammalian genomes. Almost half of the human genome and as much as 40% of the mouse genome is composed of repetitive DNA sequences. The comparison of human and mouse genomes revealed a spatial concordance in positioning of SINE but not LINE repeats, indicating evolutionary pressure to maintain and/or exclude these repeats from orthologous regions. We hypothesized that this phenomenon is due to a negative influence of SINE repeats on gene expression and counter selection over evolution, resulting in exclusion of these repeats from vulnerable genomic environments. To test the capacity of SINE B1 elements in promoting gene silencing, we generated a system where the luciferase gene is under the control of three different mouse gene promoters (cdkn2a, p14arf and mlh1), and we inserted two and four copies of SINE B1 elements upstream to these promoters. Using this in vitro system, we found that SINE B1 elements can influence the activity of downstream gene promoters, with acquisition of DNA methylation and loss of activating histone marks, thus resulting in a repressed state. Interestingly, SINE sequences themselves do not immediately acquired DNA methylation, but became marked by H3K9me2 and H3K27me3. Moreover, gain of DNA methylation depended on cryptic genomic methylation centers rather than spreading from SINE B1 repeats. Since mouse SINE B1 elements caused transcriptional repression, we sought to investigate whether human SINE Alu repeats could have the same effect. The human E-cadherin gene has three SINE Alus adjacent to the 3’ region of its CpG island, and in reporter assays the removal of these repeats resulted in higher, stable promoter activity. Genome-wide analysis of SINE repeats distribution in the human and mouse genomes showed that they are excluded from proximal promoters and their enrichment is directly correlated with the presence of USF1, USF2 and CTCF binding, proteins with insulator function. In conclusion, our work supports the concept that SINE repeats interfere negatively with gene expression and that their presence near gene promoters is dependent on, and co-evolved with the presence of insulator elements. 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 2791. doi:10.1158/1538-7445.AM2011-2791
Abstract 234: Inhibition of the NOTCH transcription factor complex by a novel hybrid protein leads to effective tumor therapy.
Authors: Agamemnon A. Epenetos, Christina Kousparou, Spyros Stylianou, Mahendra Deonarain, Aleksandra Filipovic
Journal: Cancer Research (2013)

Abstract The Notch pathway has been implicated in the generation and propagation of cancer stem cells and is thus an attractive target for therapy. We have generated a hybrid protein (Antp-DNMAML) consisting of the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion inhibiting Notch, and the cell penetrating peptide Antennapedia (Antp). Results indicate that the Antp-DNMAML translocates into the nucleus, suppresses Notch activation, reverts the transformed phenotype, inhibits the anchorage-dependent growth and induces self contact inhibition and apoptosis in tumorigenic human breast cancer cells. More significantly, there is direct evidence that inhibiting Notch signaling at the transcriptional level with the Antp-DNMAML protein, suppresses the expression of downstream Notch targets and inhibits tumor growth in nude mice, without organ or systemic toxicity. In summary, intracellular delivery of dominant-negative transcription complex proteins using the Antp platform is a new and specific approach for cancer therapy . Citation Format: Agamemnon A. Epenetos, Christina Kousparou, Spyros Stylianou, Mahendra Deonarain, Aleksandra Filipovic. Inhibition of the NOTCH transcription factor complex by a novel hybrid protein leads to effective tumor therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 234. doi:10.1158/1538-7445.AM2013-234
Evaluation of a Protocol for Post-Mortem Examination of Stillbirths
Authors: Robert F. Mueller, Virginia P. Sybert, Jennifer Johnson, Zane A. Brown, Wei-Jen Chen
Journal: New England Journal of Medicine (1983)

A variety of procedures have been recommended for post-mortem examination of stillbirths to determine the cause of the loss of the pregnancy and to provide an estimate of the risk of recurrence. We studied the relative usefulness of several such techniques, including gross and microscopical autopsy, photography, radiography, bacterial cultures, and chromosome studies. In 44 (35 per cent) of 124 cases of stillbirth or early neonatal death, structural physical abnormalities were evident at autopsy. In 35 of the 44 cases the abnormalities were due to chromosomal, single-gene, or polygenic disorders. The single most useful examination was the gross autopsy. Analysis of the various procedures suggests that when resources are limited, gross autopsy, photography, radiography, and bacterial cultures should be performed in all cases of stillbirth and early neonatal death, but that karyotyping and histopathology may be used selectively. This approach should minimize the use of expensive, low-yield procedures without compromising the ability to provide information for purposes of genetic counseling. (N Engl J Med 1983; 309:586–90.)
Impact of Uterine Fibroids on ART Outcome
Authors: D L Healy
Journal: Environmental Health Perspectives (2000)

Our objective was to investigate the effect of subserosal (SS), intramural (IM), and submucosal (SM) fibroids on the outcome of assisted reproductive technology (ART) treatment. A retrospective comparative study at a tertiary referral center for infertility was designed. The treatment outcome of 106 ART cycles in 88 patients with uterine fibroids (33 SS, 46 IM without cavity distortion, 9 SM) was compared with that of 318 ART cycles in age-matched patients without fibroids. The main outcome measure(s) were the findings on transvaginal uterine ultrasonography performed before the initiation of treatment and pregnancy and implantation rates. The pregnancy rates per transfer were 34.1, 16.4, 10, and 30.1% in the patients with SS fibroids, IM fibroids, SM fibroids, and no fibroids, respectively. The implantation rates were 15.1, 6.4, 4.3, and 15.7%, respectively. Both rates were significantly lower in patients with IM fibroids than in those with SS fibroids or no fibroids. We conclude that pregnancy and implantation rates were significantly lower in the groups of patients with IM and SM fibroids, even when there was no deformation of the uterine cavity. Pregnancy and implantation rates were not influenced by the presence of SS fibroids. Surgical or medical treatment should be considered in infertile patients who have IM and/or SM fibroids before resorting to ART treatment.
From Alchemy to Fluid, Electrolyte, and Acid–Base Disorders
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2014)

The article by Berend et al.1 in this issue of the Journal is the first in a series of review articles that consider approaches to the understanding and management of fluid, electrolyte, and acid–base disorders. These disorders are among the most common conditions that we encounter as clinicians.The topics discussed are long-standing concerns. The history of salt and its medicinal uses goes back for millennia,2 and compounds that we currently call acids and bases3 were identified in ancient times. During the Middle Ages, acids were known by alchemists, who were seeking to change base metals into gold. However, current . . .
A8.27 Intraarticular drug delivery of anti-HMGB1 in hyaluronan gels for osteoarthritis treatment
Authors: C Aulin, H Erlandsson Harris, L Klareskog
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Joint pain due to degeneration of cartilage tissue in osteoarthritis is a major problem affecting people of different ages and there are no long-term solutions available today. During recent years means suppression of inflammation that stops joint destruction have been developed and there is now a need for new approaches to stimulate repair. This should preferably be done without use of complicated cell therapies, and an opportunity to accomplish such development is provided by the application of new, injectable derivatives of hyaluronan. The cross linking chemistry applied here is a very rapid reaction between carbazate moieties on one component and aldehyde groups in the other, where a solid gel is formed within 30 s. HMGB1 is an endogenous molecule released from activated immune cells as well as dying cells with both proinflammatory and osteoclast-activating features. HMGB1 blockade is proven effective in experimental models of RA and the presence of extracellular HMGB1 is reported in OA specimens. The aim of this study was to evaluate the effect of HMGB1 blockade on cartilage repair and evaluate drug delivery into the joint using hyaluronan gels in an experimental osteoarthritis model in mice. <h3>Materials and methods</h3> OA was induced in mice by surgically destabilising the knee joint through anterior cruciate ligament transection. Anti-HMGB1 encapsulated in the gel was injected intraarticularly. After 8 weeks the animals were sacrificed and knees processed for histology. Sections were stained with Safranin-O and HMGB1 and scored blinded. <h3>Results</h3> We demonstrated that cartilage could be rescued by treatment with anti-HMGB1 in the OA model. HMGB1 staining in the cartilage specimens showed intra and pericellular expression in chondrocytes of proteoglycan depleted areas in articular cartilage. HMGB1 was also present in ligaments, synovia and osteophytes. A surprising observation was that also the gel alone showed improvement of cartilage. The negative impact of endogenous aldehydes on chondrogenesis have been demonstrated in a number of studies. The gel precursors carry aldehyde and hydrazide functional groups for the gel formation and we believe that interaction and neutralisation of endogenous aldehydes in the joint cavity may have affected cartilage healing. <h3>Conclusions</h3> The hyaluronan hydrogel has shown promising results for cell free regeneration therapies by local treatment in the joints. We showed that blocking of HMGB1 improved the cartilage regeneration in experimental OA and the hyaluronan gel in itself carried anti-inflammatory properties.
Multiple Hepatitis Viruses in Multiple Attacks of Acute Viral Hepatitis
Authors: James W. Mosley, Allan G. Redeker, S. M. Feinstone, R. H. Purcell
Journal: New England Journal of Medicine (1977)

We evaluated the causes of 30 episodes of acute viral hepatitis in 13 patients who had multiple attacks. Two (seven per cent) of 30 bouts were caused by hepatitis A virus, and 12 (40%) by hepatitis B virus. No patient, however, had more than one attack with the serologic characteristics of Type A or Type B disease. Thus, there were 16 bouts (53 per cent) not attributable to either of the two recognized hepatitis viruses. None of these "non-A, non-B" episodes, evaluated for infectious mononucleosis and cytomegalovirus infection, could be ascribed to either. From this evidence, therefore, it appears that the clinical syndrome of viral hepatitis is produced not only by the two viruses (hepatitis A virus and hepatitis B virus) recognized since the 1940's but also, in all probability, by two non-A, non-B agents.
Abstract 1219: Defective catagen entry in EGFR deficient skin precedes cutaneous inflammation
Authors: Kyle J. Bichsel, Jessica A. Gaulter, Dennis Porto, Courtney Foote, Laura A. Hansen
Journal: Cancer Research (2012)

Abstract Treatment of cancer patients with epidermal growth factor receptor (EGFR) inhibitors causes perifollicular inflammation in the skin. Mouse models with EGFR deficiency predicted this folliculitis and revealed that abrogation of EGFR disrupts hair follicle cycling. We hypothesized that the defect in progression through catagen resulting from EGFR deficiency causes cutaneous inflammation. EGFR regulation of the hair cycle and inflammation was investigated using skin-targeted deletion of Egfr (Krt14-Cre+/Egfrfl/fl mice). Hair cycle stage was assessed using histological criteria, analysis of follicular apoptosis and the position of the dermal papillae. Dorsal hair follicles of control mice synchronously entered catagen at 17 d and progressed to telogen by 21 d. In contrast, Egfr mutant follicles asynchronously entered catagen, with some follicles beginning catagen at 18 d or later, and others remaining in anagen through 24 d. Mast cells were examined because follicular mast cell precursors can facilitate the transition into catagen after their maturation and degranulation. Failed catagen progression preceded an inflammatory response in the mutant skin, which was characterized by a 40% or more increase in mast cell numbers beginning at 21 d. Mast cells in mutant skin were more likely to be degranulated as well. Neutrophils and macrophages increased in mutant skin by 28 d, subsequent to the increase in mast cell numbers. Transcriptional profiling was performed at 17 d, the time of normal catagen onset, using follicular RNA obtained from laser capture microdissection to identify EGFR-regulated mediators of the inflammatory response. In silico analyses of these data identified increased expression of 12 immune function genes in mutant hair follicles including the mast cell proteases Chymase and Tryptase. Additionally, the class I major histocompatibility (MHC) molecules H2-Q9, H2-Q7 and H2-D1 and class II MHC molecules H2-Eb1, H2-Dmb1 and H2-Dmb1/2 were over-expressed in mutant hair follicles consistent with a role for adaptive immunity in cutaneous inflammation following asynchronous catagen. Thus, an aberrant catagen transition and upregulation of pro-inflammatory genes preceded folliculitis in Egfr mutant skin. 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 1219. doi:1538-7445.AM2012-1219
OP0179 Apl-1, A Peptide as Immunomodulator for the Treatment of Juvenile Idiopathic Arthritis
Authors: M.D.C. Dominguez Horta, N. Lorenzo, D. Cantarra
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by autoimmune arthritis of unknown cause. Current treatment focuses on reduction of inflammation through anti-inflammatory and immunosuppressive strategies, including methotrexate and anti-TNF-α therapies [1]. But, some children with JIA do not respond or are intolerant to treatment with disease-modifying antirheumatic drugs [2]. Induction of peripheral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases <h3>Objectives</h3> To evaluate the therapeutic potentialities of an altered peptides ligand (APL) derived from human heat-shock protein 60 (hHsp60) for the treatment of JIA. <h3>Methods</h3> A novel epitope of T cells located in the N terminal region of hHsp60, an autoantigen involved in the pathogenesis of autoimmune arthritis, was identified by bioinformatics tools and an APL (called APL-1) was designed starting from this epitope [3]. We investigated the ability of this peptide for inducing regulatory T cells (Treg cells) in <i>ex vivo</i> assays using mononuclear cells isolated from JIA patients. In addition, we evaluated the therapeutic effect of APL-1 in collagen induced arthritis (CIA) model. Clinical score, TNFα levels and histopathology were monitored. <h3>Results</h3> APL-1 induced a substantial increment of Treg cells in <i>ex vivo</i> assays using PBMC from JIA patients. The evaluation of this peptide in CIA model shows a significant reduction of arthritis score in treated mice, without present any histological damage in the joints at day 60. In addition therapy with the peptide induced a significant reduction of TNFα levels. <h3>Conclusions</h3> The results shown here reinforce the therapeutic possibilities of APL-1 as a candidate drug for treatment of JIA. Interference of the pathogenic T cell function in a specific manner using an APL derived from an autoantigen that can induce tolerance mediated by activation of Tregs as shown here, represents an attractive therapeutic approach for autoimmune diseases. <h3>References</h3> Prakken B, Albani Se, Martini A (2011) Juvenile idiopathic arthritis. Lancet. 377:2138–49. Horneff G, Schmeling H, Biedermann T et al (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann. Rheum. Dis. 63:1638–44. MC Domínguez, N. Lorenzo, A. Barbera et al (2011) An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic responses in an animal model of adjuvant induced arthritis. Autoimmunity. 44:471-82. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1908
Abstract 1817: Sex disparities in colorectal cancer incidence by anatomic subsite, race and age
Authors: Gwen A. Murphy, Susan S. Devesa, Peter D. Inskip, Katherine A. McGlynn, Michael B. Cook
Journal: Cancer Research (2010)

Abstract Background: Colorectal cancer remains the fourth most common cancer diagnosed and the second most common cause of cancer death in the United States. Though incidence and mortality rates have declined in recent years, the burden of disease is disproportionate; rates are higher in men than women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than whites or blacks have not been frequently reported. Methods: To examine colorectal cancer rates by sex across anatomic subsite, age, and racial/ethnic groups, we used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992-2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; male-to-female incidence rate ratios (MF IRR) and 95% confidence intervals were also calculated. Results: Among both males and females, total colorectal cancer rates were highest among Blacks (71.0 and 54.8 per 100,000 person-years, respectively) and lowest among Hispanics (47.8 and 32.4). Rates of proximal colorectal cancer were higher than distal and rectal sites for all race/ethnicities. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from &amp;lt;1.0 at ages &amp;lt;50 years to 1.4-1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently &amp;lt;1.5 and varied little with age; among American Indian/Alaska Natives it was &amp;lt;1.0 across all ages. Conclusion: The MF IRR for colorectal cancer varies markedly according to subsite and age but less by racial/ethnic group. These findings may reflect differing exposure to, or metabolism of, hormonal or environmental elements and may have consequences for screening messages. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1817.
A Rare Case of Pemphigus Vegetans Mimicking Malignancy on F-18 FDG PET/CT
Authors: Maria M. D'souza, Paschal V. D'souza, Abhinav Jaimini, Rajnish Sharma, Madhavi Tripathi, Dinesh Singh, Anupam Mondal
Journal: Clinical Nuclear Medicine (2011)

A 42-year-old man with a history of chronic smoking and alcoholism was suspected to harbor a malignancy involving the perioral region and the scalp. He underwent an F-18 FDG PET/CT scan which revealed abnormal F-18 FDG accumulation in the oral mucosa and lips, extending to the nose, scalp, and bilateral cervical lymph nodes. Further work-up ultimately revealed the lesions to be secondary to pemphigus vegetans. Pemphigus vegetans is a rare variant of pemphigus vulgaris, an autoimmune bullous cutaneous disorder and involves mainly the flexural regions of the body. Unlike pemphigus vulgaris, lesions of pemphigus vegetans present as heaped up, eroded, and ulcerative plaques in the intertriginous regions of the body. Occasional lesions may be present on scalp and elsewhere in the Hallopeau variant of the disease. The use of F-18 FDG PET in the field of oncology is rapidly evolving; however, it is not tumor specific. The integration of CT into PET has increased the specificity of this modality. Nevertheless, there are many physiologic and benign conditions that may result in high accumulation of FDG, and may mimic malignancy. Familiarity with F-18 FDG-avid nonmalignant lesions may extend the use of F-18 FDG PET imaging beyond the field of oncology. To the best of our knowledge, this is the first description of PET/CT findings in pemphigus vegetans.
The role of real-time virtual sonography in the management of enhancing breast lesions on contrast-enhanced MRI.
Authors: S Nakano, K Fujii, K Yorozuya, Y Mouri, T Fukutomi, T Ishiguchi, O Arai, T Mitake
Journal: Cancer Research (2009)

Abstract Abstract #4001 [Purpose]&amp;#x2028; The aim of this study was to evaluate the role of real-time virtual sonography (RVS) in the management of enhancing breast lesions visualized with contrast-enhanced MRI.&amp;#x2028; [Materials]&amp;#x2028; Between April 2006 and May 2008, 92 women underwent breast MRI at our hospital. Of these 92 patients, 55 underwent MRI for staging of known breast cancer, and the remaining 37 underwent MRI for problem solving, including abnormal findings at physical examination or on conventional images. All patients were examined using mammography, sonography, MRI and RVS. The RVS system is capable of superimposing a sonography image with the MRI image of the same section in real time using a position tracking system with a magnetic sensor. Breast MR images were obtained on a 1.5-T imager using a flexible body surface coil, with the patient in the supine position.&amp;#x2028; [Results]&amp;#x2028; Overall sensitivity for detecting primary breast cancer was 74% (43/58) for mammography, 93% (54/58) for sonography, 97% (56/58) for MRI, and 97% (56/58) for RVS. Incidental enhancing / suspicious lesions (IELs) which were not predicted by the previous conventional imaging techniques were found in 55% of the patients (51/92),. Of these, 59% (24/41) of IELs could be identified only on repeated sonography, but 85% (35/41) of them were identified easily using the RVS system (p&amp;lt;0.05). The RVS system was able to project enhanced MRI information onto a body surface correctly while checking sonography form images without the use of large-scale equipment. Histologically, 10% (4/41) of the IELs were invasive ductal carcinoma.&amp;#x2028; [Conclusions]&amp;#x2028; The present results suggest that the RVS system offers excellent accuracy for identification of enhancing breast lesions. RVS can accurately select the cases in which MR guided biopsies are required. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4001.