tbuckley/cabot-search huggingface dataset:
Abstract 2550: Expanded simple tandem repeat (ESTR) mutations in offspring of benzo(a)pyrene exposed DNA repair deficient male mice
Authors: Roger Godschalk, Nicole Verhofstad, Joost Linschooten, Jan Van Benthem, Harry Van Steeg, Carole Yauk, Frederik-Jan Van Schooten
Journal: Cancer Research (2012)

Abstract Germ line mutations can be transmitted to the offspring and may thus affect an infinite number of generations thereafter. To study germ line mutations, expanded simple tandem repeats (ESTR) can be used as a sensitive tool, because they are known to be highly unstable and therefore exhibit high mutation rates. This facilitates the assessment of germ line mutations in a relatively small number of offspring following exposures that may pose a genetic risk to the germ line. We used two ESTR loci Ms6-hm and Hm-2 in families of benzo(a)pyrene (BaP) exposed and unexposed male mice, proficient or deficient for global genome repair (Xpc-/-). Male mice (C57BL/6) were exposed to BaP during 6 weeks (13 mg/kg bw, 3 times per week) and were crossed with female mice (Balb/C) 6 weeks after the last exposure to obtain offspring and to ensure the analysis of mutations originating from spermatogonial stem cells. The overall ESTR mutation rate at both ESTR loci, irrespective of the DNA repair capacity, was higher in offspring of benzo(a)pyrene exposed mice than in control mice (9.4% vs. 4.5%, P=0.054). This effect was predominantly seen in BaP exposed DNA repair deficient Xpc-/- mice; mutation frequencies were 12.5% in the exposed group (12 out of 96 offspring carried a mutant allele) and 3.4% in the unexposed group (3 out of 87), respectively (P=0.024). In DNA repair proficient mice, BaP was unable to increase the mutation frequency transmitted to the offspring (5.8% vs. 5.5% for offspring of exposed and unexposed fathers). These results indicate that analysis of tandem repetitive sequences is a sensitive method for the detection of germline mutations transmitted to the offspring and that the environmental mutagen BaP is able to induce germ line mutations in DNA repair deficient mice. 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 2550. doi:1538-7445.AM2012-2550
Abstract 2173: Negative transcriptional regulation of the human type III TGFβ receptor in ccRCC
Authors: Simon J. Cooper, Christina Von Roemeling, Laura Marlow, Han W. Tun, John A. Copland
Journal: Cancer Research (2011)

Abstract Renal cell carcinoma (RCC) accounts for 3% of all malignancies reported each year making it the sixth leading cause of cancer death in the United States. Within this year more than 50,000 individuals will be diagnosed with RCC and around 12,000 will die from this disease. Out of these RCCs the most frequently diagnosed form is clear cell renal cell carcinoma (ccRCC) which accounts for approximately 80% of all RCCs. We have previously identified through genomic profiling that loss of the type II and III TGFβ receptors in the progression of this disease lead to loss of TGFβ responsiveness and suggests a role for dysregulated TGFβ signaling in RCC progression and metastasis. Restoration of the TGFβ receptor type III (TβRIII) leads to apoptosis in RCC cell lines (Margulis et al. 2007) suggesting that re-expression of TβRIII is an attractive method for intervention of ccRCC. Recently we identified that loss of TβRIII is an early event in ccRCC and that this loss is not through epigenetic silencing but due to the loss of transcriptional regulation. The transcription factor GATA3 was identified to be a positive regulator of TβRIII expression through its actions on the proximal promoter of TβRIII. Through deletion analysis we have now identified a region within the proximal promoter that contains a number of putative transcription factor binding sites that are capable of negatively regulating the expression of TβRIII. We have identified that one of these transcription factors is over-expressed in ccRCC patient matched renal tissue samples and that silencing of this transcription factor through lentiviral shRNA, leads to a three fold induction of endogenous TβRIII in ccRCC cell lines. Furthermore, loss of this transcription factor in ccRCC cell lines leads to decreased cell proliferation when compared to non-target infected controls. Further evaluation of these putative negatively regulating transcription factors and their actions upon the proximal promoter of TβRIII are being analyzed utilizing EMSA and ChIP assays. These investigations will identify novel molecular targets that through their dysregulation will have the potential to up-regulate TβRIII in ccRCC inducing apoptosis within these cells. Together these findings will allow for a deeper molecular understanding of the events taking place in ccRCC. 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 2173. doi:10.1158/1538-7445.AM2011-2173
Role of Helper, Suppressor and B-Cell Defects in the Pathogenesis of the Hypogammaglobulinemias
Authors: Frederick P. Siegal, Marta Siegal, Robert A. Good
Journal: New England Journal of Medicine (1978)

We investigated suppressor and helper T cells in 19 patients with variable immunodeficiency to assess the possibility that defective interactions among these cells and B lymphocytes are the chief cause of the inadequate plasma-cell development and hypogammaglobulinemia characterizing these syndromes. We accomplished functional separation of the two T-cell subsets, using irradiation, which selectively inactivates T-cell suppressors. The patient B lymphocytes were usually capable of some differentiation into plasma cells when co-cultured with T cells manipulated to optimize helper effects. Eighteen of 19 patients showed quantitively poor plasma-cell production even under these conditions. However, only one had defective enough helper function, and only one sufficiently excessive suppressor activity for these factors to be considered the major pathogenetic process in each case. Since neither an absolute defect in B cells nor consistent abnormalities in modulator T cells were demonstrable in most patients, other explanations must be sought for the mechanisms underlying this form of primary immune deficiency. (N Engl J Med 299:172–178, 1978)
Pseudo-von Willebrand's Disease
Authors: Harvey J. Weiss, Dominique Meyer, Rosanne Rabinowitz, Genevieve Pietu, Jean-Pierre Girma, William J. Vicic, John Rogers
Journal: New England Journal of Medicine (1982)

Original Article from The New England Journal of Medicine — Pseudo-von Willebrand's Disease — An Intrinsic Platelet Defect with Aggregation by Unmodified Human Factor VIII/von Willebrand Factor and Enhanced Adsorption of Its High-Molecular-Weight Multimers
Abstract LB-349: Differential expression of microRNAs in oligodendrogliomas of different grades of malignancy
Authors: Luciano Neder Serafini, Rodrigo A. Panepucci, Daniela P. C. Tirapelli, Viviane C. Oliveira, Patricia Monteiro, Deise L. Simoes, Wilson A. Silva, Carlos G. Carlotti
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) are large tiny regulatory RNAs found ubiquitously in plants, insects and mammals. More recently, miRNAs have also been implicated in oncogenesis, acting as tumor suppressors or oncogenes. The role of miRNAs in glioma progression has been intensively investigated chiefly in glioblastomas, the most prevalent malignant glioma. However, there are few data regarding to miRNA expression in oligodendrogliomas. The main goal of this study was to evaluate miRNAs and mRNAs that are differentially expressed in a series of grade II and III oligodendrogliomas (7 per group, with duplicates) in order to obtain miRNAs that correlate with their putative target-mRNAs. After microdissection and diagnosis confirmation, miRNAs and mRNAs expression were evaluate using microarray-based expression profiling platforms (723 transcripts and 41,000 genes, respectively) at same tumor specimens. As controls, samples of temporal lobe white matter from patients operated for clinical intractable complex partial seizures were used (n = 16). Fifteen and 29 miRNAs transcripts were relatively hyper- and hypoexpressed in anaplastic oligodendrogliomas; however, after matching of miRNAs and putative target-mRNAs expressions, only 4 miRNAs transcripts remained overexpressed in which target genes have pivotal role in key cell signaling pathways. Similarly, 20 of 29 miRNAs transcripts remained down regulated. Of these, 4 miRNAs that were previously described as to be involved in cell differentiation in embryonic stem cells (ESC) are being validated through their target genes by real time PCR. Herein, we were able to identify putative oncogenic miRNAs that can be operating in oligodendrogliomas progression, expanding our knowledge about tumor biology and disclosing possible molecular targets for treatment proposals. Support: FAPESP (Grant Proc. No. 05972–2) 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 LB-349. doi:10.1158/1538-7445.AM2011-LB-349
HISTORIA NATURAL DE LOS TUMORES QUÍSTICOS DE PÁNCREAS: CRITERIOS CLINICOS Y ECOENDOSCÓPICOS DE MALA EVOLUCIÓN
Authors: C Padilla, C González, B Merino, K Klimova, C Carbonell, JC Ávila, H Martínez, O Nogales, J García, P Menchén
Journal: Endoscopy (2014)

Introducción: La historia natural de las lesiones quísticas de páncreas no es del todo conocida y el diagnóstico de certeza es complicado.
Evaluation of Tc-99m MAG3 Dynamic Renal Scintigraphy with an Aneurysmal Type Renal Arteriovenous Fistula
Authors: YOSHIO HORITA, SATORU NAKAMURA, SADAMU HIRASHIMA, MASATO TADOKORO, KOUICHI TAURA, NAOFUMI SUYAMA, ICHIRO SAKAMOTO, MASAHARU NISHIKIDO, MASANOBU MIYAZAKI, SHIGERU KOHNO
Journal: Clinical Nuclear Medicine (2003)

HORITA, YOSHIO M.D.; NAKAMURA, SATORU; HIRASHIMA, SADAMU; TADOKORO, MASATO; TAURA, KOUICHI; SUYAMA, NAOFUMI; SAKAMOTO, ICHIRO; NISHIKIDO, MASAHARU; MIYAZAKI, MASANOBU; KOHNO, SHIGERU Author Information
SM-02 * LEVETIRACETAM USAGE IN POST-OPERATIVE SEIZURE MANAGEMENT IN MALIGNANT GLIOMA
Authors: J. Kang, A. Desjardins, P. Healy, J. Herndon, E. Lipp, K. Peters, G. Vlahovic, J. Sampson, H. Friedman, A. Friedman, C. Adamson
Journal: Neuro-Oncology (2014)

BACKGROUND: There is a lack of consensus in the use of newer-generation anti-epileptic drugs (AEDs) as prophylaxis in patients with malignant glioma (MG) who undergo surgical resection. The rate of seizure occurrence in MG is less than low-grade gliomas, but due to the debilitating nature of seizures, clinicians routinely prescribe prophylactic AEDs. Recommendations were last published in 2000 by the American Academy of Neurology based on research of older generation AEDs. Levetiracetam (LEV) is a newer generation AED with an improved safety profile and proven efficacy in heterogeneous patient populations, but its efficacy has yet to be determined in MG patients. METHODS: A retrospective analysis of AED usage was conducted among 114 patients diagnosed with MG (WHO Grade III-IV) who underwent initial resection at a single institution during 2011-2012. Demographics, comorbidities, tumor and surgical characteristics, AED usage, toxicity and seizure occurrence were reviewed. Seizure history was characterized prior to and up to 6 months after surgery. Logistic regression was used to evaluate the association of LEV prophylaxis and other risk factors with post-operative seizure occurrence. RESULTS: Patients were male (58%), had a gross total resection (88%), a history of seizures (44%), and received LEV pre-operatively (45%). Post-operatively, 91% received LEV of which 25% experienced a seizure. Side effects of LEV use were rare (n = 10, 10%), and included irritability, somnolence, psychiatric disturbances, and thrombocytopenia. Patient's age was a significant predictor of seizure occurrence. Older patients had a higher risk of seizure in the 6 months post-operatively (OR = 2.6, 95% CI 1.10-6.35, p = 0.0327). CONCLUSIONS: LEV is well tolerated in MG patients undergoing resection. Older age is associated with post-operative seizure occurrence. Future studies need to assess the effectiveness of LEV in reducing post-operative seizure recurrence in this population in comparison to other AEDs.
PTU-091 Transient Elastography as a Predictor of Oesophageal and Gastric Varcies: Abstract PTU-091 Table
Authors: A Bond, K Koss, V Maddirala
Journal: Gut (2013)

<h3>Introduction</h3> Screening for varices with two yearly gastroscopy is recommended practise for all patients with liver cirrhosis. Prevalence of oesophageal or gastric varices in patients with liver cirrhosis varies in the literature from 30–70%. The Aim of this study was to analyse if the result of transient elastography (TE) can be used to predict the risk of developing gastric and/or oeosphageal varices in cirrhotic patients. We compared this data with endoscopic and radiological evidence of portal hypertension. <h3>Methods</h3> We analysed data of 807 patients who underwent TE examination at East Cheshire NHS Trust and identified 103 patients with suspected liver cirrhosis (liver stiffness score of &gt;12.5 kPa). The cut off F4 liver fibrosis/cirrhosis varies between 14.5 kPa to 18.2 kPa for different aetiologies of liver cirrhosis. We evaluated results of TE against upper GI endoscopy and abdominal ultrasound/CT. <h3>Results</h3> 26% of patients with F4 liver fibrosis/cirrhosis were found to have oesophageal/gastric varices at endoscopy. A total of 37% patients had evidence of portal hypertension on USS or CT. Only 41% of patients with splenomegaly were found to have oesophageal/gastric varices. 78% of those found to have varices had a liver stiffness score of &gt;25 KPa. <h3>Conclusion</h3> We postulate that TE helps us to stratify a patient’s risk of developing oesophageal/gastric varices, according to their liver stiffness score. The likelihood of developing oesophageal/gastric varcies increases with increased liver stiffness. Patients with liver stiffness scores lower than 25kPa may avoid unnecessary upper GI endoscopy. <h3>Disclosure of Interest</h3> None Declared
Abdominal Aortic Aneurysm Visualized With Hepatobiliary Scintigraphy
Authors: JEANNE STRYKER, ALAN SIEGEL
Journal: Clinical Nuclear Medicine (1997)

A 72-year-old man, who had acute right upper quadrant pain, underwent hepatobiliary scintigraphy for the evaluation of suspected acute cholecystitis. A large focus of increased activity identified in the midabdomen in the initial images faded during the first 10 minutes and was believed to represent an abdominal aortic aneurysm. A correlative CT verified the finding.
Pharmacokinetics of Indomethacin in the Neonate
Authors: Alan R. Brash, Docia E. Hickey, Thomas P. Graham, Mildred T. Stahlman, John A. Oates, Robert B. Cotton
Journal: New England Journal of Medicine (1981)

To identify factors affecting the efficacy of indomethacin in closing symptomatic patent ductus arteriosus (PDA), we studied the pharmacokinetics of intravenous indomethacin, 0.2 mg per kilogram of body weight, in 35 premature infants with symptomatic PDA. Most infants responded to indomethacin with ductus constriction. Indomethacin infusions that were ineffective (seven doses in six patients) were associated with significantly faster clearance, a shorter half-life, and lower plasma levels (p less than 0.05). Six infants had later reopening of the ductus. All six received indomethacin in the first postnatal week; they could not be distinguished from infants with permanent closure on the basis of indomethacin kinetics, but they were of low gestational age. There was a 20-fold variation in plasma indomethacin levels 24 hours after a dose. In view of this variation and the relation between plasma levels and ductus constriction, we suggest that measurement of the plasma indomethacin level could be of value in infants with no response to a first dose.
Abstract 3955: Epigenetic silencing of microRNA-34b/c plays a pivotal role in pathogenesis of small-cell lung cancers
Authors: Norimitsu Tanaka, Shinichi Toyooka, Junichi Soh, Yuho Maki, Takayuki Muraoka, Tsuyoshi Ueno, Keiju Aokage, Hiroaki Asano, Kazunori Tsukuda, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi
Journal: Cancer Research (2011)

Abstract Background: Lung cancer is the leading cause of cancer-related death in the world. Small-cell lung cancer (SCLC) accounts for approximately 13% of lung cancers. Although chemotherapy results in initially high response rates, survival of patients with extensive stage disease is dismal. MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes that regulate cell proliferation and apoptosis. Recent studies have shown that, in cancer cells, expression of some miRNAs is silenced with DNA methylation in promoter region. Aberrant methylation of miR-34b/c has been reported in human malignancies, but not in SCLCs, causing up-regulation of oncogenes. In this study, we investigated the methylation and expression status of the miR-34b/c and the anti-proliferative effect by induction of miR-34b/c in SCLCs. Methods: We examined 11 SCLC cell lines and 6 resected primary SCLC tumors (one tumor treated with preoperative chemotherapy and five without preoperative chemotherapy). Methylation and expression status of miR-34b/c were determined by methylation-specific PCR and quantitative PCR, respectively. Colony formation assay was applied to examine the anti-proliferative effect by induction of miR-34b/c and scramble sequence control with plasmid vector. The ability of cell migration was examined using cell migration assay. Results: Aberrant methylation of miR-34b/c was found in 7 (64%) of 11 SCLC cell lines and 3 (50%) of 6 primary SCLC tumors. Expression of miR-34b/c in all methylation cell lines was silenced and restored with 5-aza-2’-deoxycytidine treatment, indicating that methylation caused gene silencing. Ectopic induction of miR-34b/c gene in SCLC cell line (H1048) showed significant inhibition of colony formation compared with induction of control vector, demonstrating anti-proliferative effect of miR-34b/c on SCLC. The cell migration was also significantly inhibited by induction of miR-34b/c in SCLC cell line tested. Conclusion: Our results demonstrated that miR-34b/c methylation is frequent in SCLCs and induction of miR-34b/c inhibits the cell proliferation and migration, resulting that miR-34b/c silencing plays an important role in pathogenesis of SCLCs. 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 3955. doi:10.1158/1538-7445.AM2011-3955
Measurement of the Urinary Lactate:Creatinine Ratio for the Early Identification of Newborn Infants at Risk for Hypoxic–Ischemic Encephalopathy
Authors: Chao-Ching Huang, Shan-Tair Wang, Ying-Chao Chang, Kung-Ping Lin, Pei-Lin Wu
Journal: New England Journal of Medicine (1999)

Newborn infants with perinatal asphyxia are prone to the development of hypoxic–ischemic encephalopathy. There are no reliable methods for identifying infants at risk for this disorder.
Regional Heparinization for Hemodialysis
Authors: John F. Maher, Louis Lapierre, George E. Schreiner, Mario Geiger, Frederic B. Westervelt
Journal: New England Journal of Medicine (1963)

SINCE the clinical application of extracorporeal hemodialysis requires the addition of an anticoagulant to the blood, hemorrhagic complications may occur in the patient.In the usual procedure, 6000 to 9000 U.S.P. units of heparin sodium (about 60 to 90 mg.) are added to the blood used to prime the artificial kidney. When the dialyzer is connected to the patient, there is a systemic effect. Anticoagulant activity is monitored by serial determinations of clotting times by the Lee and White method. When the clotting time falls below sixty minutes, 1000 to 2000 U.S.P. units (about 10 to 20 mg.) . . .
Timing of Enteral Feeding in Cerebral Malaria in Resource-Poor Settings: A Randomized Trial
Authors: Richard Maude, Md Gofranul Hoque, Md Mahtab Uddin Hasan, Md Abu Sayeed, Shahena Akter, Rasheda Samad, Badrul Alam, Emran Bin Yunus, Md Ridwanur Rahman, Md Waliur Rahman, Romal Chowdhury, Tapan Seal, Prakaykaew Charunwatthana, Christina Chang, Nicholas White, Md Abul Faiz, Nicholas Day, Arjen Dondorp, Md Amir Hossain
Journal: Journal of Infection (2011)
THU0325 Elevated IgG4 Serum Levels Among Primary Sjogren’s Syndrome Patients: Do they Unmask Underlying IgG4-Related Disease?
Authors: C. P. Mavragani, G. E. Fragoulis, D. Rontogianni, M. Kanariou, H. M. Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IgG4 related disease (IgG4-RD) primary Sjogren's syndrome (pSS) share some common clinical, serological and histopathological characteristics. <h3>Objectives</h3> To determine whether a subset of primary Sjogren's syndrome patients fulfill the recently proposed criteria for IgG4 related disease. <h3>Methods</h3> Serum IgG4 levels were measured in 133 pSS patients and 49 healthy blood donors (HBD). 74 lupus patients and 54 patients with rheumatoid arthritis (RA) were served as disease controls. Immunohistochemical IgG4 analysis was performed in paraffin-embedded minor salivary gland (MSG) tissues. <h3>Results</h3> Raised IgG4 serum levels (&gt;135mg/dl) were detected in 10 out of 133 pSS patients [(7.5%), "High-IgG4" group), in 8 out of 74 lupus patients (10.8%), in 7 out of 54 (12.9%) RA patients and in one out of 49 HBD (2%). Compared to the "Normal-IgG4" pSS group (&lt;135mg/dl), "High-IgG4" patients exhibited increased prevalence of IgG4-related features (autoimmune cholangitis and pancreatitis, interstitial nephritis), lower rates of ANA positivity (p=0.03) and higher IgG2 (p=0.02) and IgE (p=0.04) levels. When the cut-off for IgG4 positivity was defined as 270 mg/ dl, the corresponding rates were 5 out of 133 (3.7%) for pSS, 3 out of 74 (4.1%) for SLE, 1 out of 54 RA (1.9%) and 0 out of 49 HBD (0%). Positive staining for IgG4+ plasma cells, with an IgG4/IgG ratio ≥40% was detected in 3/5 available MSG tissues in the "High-IgG4" group. Criteria of possible or definite IgG4-RD were fulfilled by 10 out of 133 (7.5%) of our pSS cohort. <h3>Conclusions</h3> Criteria for IgG4-RD were fulfilled by a small subset of our pSS cohort characterized by high prevalence of IgG4-related clinical, serological and histopathological features. <h3>Disclosure of Interest</h3> None Declared